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1.
Dermatologie (Heidelb) ; 75(3): 181-196, 2024 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-38366245

RESUMO

BACKGROUND: Systemic sclerosis (SSc) is a very heterogeneous, chronic, rare, but socioeconomically important disease with a severe disease course and severe impairment of the quality of life of affected patients. OBJECTIVES: Overview of the current state of research on the pathogenesis, diagnosis and therapy of SSc. METHODS: A literature search was performed. RESULTS: The pathogenesis of SSc is not fully understood. ACR/EULAR criteria allow the diagnosis of early forms of SSc. Classification into limited cutaneous SSc and diffuse cutaneous SSc is of prognostic and therapeutic relevance. New organ-specific treatment options for SSc have led to improved quality of life and prognosis.


Assuntos
Esclerodermia Difusa , Escleroderma Sistêmico , Humanos , Qualidade de Vida , Escleroderma Sistêmico/diagnóstico , Prognóstico , Progressão da Doença
2.
Geophys Res Lett ; 49(20): e2022GL099529, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36582355

RESUMO

The climate signal imprinted in the snow isotopic composition allows to infer past climate variability from ice core stable water isotope records. The concurrent evolution of vapor and surface snow isotopic composition between precipitation events indicates that post-depositional atmosphere-snow humidity exchange influences the snow and hence the ice core isotope signal. To date, however, this is not accounted for in paeleoclimate reconstructions from isotope records. Here we show that vapor-snow exchange explains 36% of the summertime day-to-day δ18O variability of the surface snow between precipitation events, and 53% of the δD variability. Through observations from the Greenland Ice Sheet and accompanying modeling we demonstrate that vapor-snow exchange introduces a warm bias on the summertime snow isotope value relevant for ice core records. In case of long-term variability in atmosphere-snow exchange the relevance for the ice core signal is also variable and thus paleoclimate reconstructions from isotope records should be revisited.

3.
J Geophys Res Atmos ; 124(6): 2932-2945, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-31218150

RESUMO

Several recent studies from both Greenland and Antarctica have reported significant changes in the water isotopic composition of near-surface snow between precipitation events. These changes have been linked to isotopic exchange with atmospheric water vapor and sublimation-induced fractionation, but the processes are poorly constrained by observations. Understanding and quantifying these processes are crucial to both the interpretation of ice core climate proxies and the formulation of isotope-enabled general circulation models. Here, we present continuous measurements of the water isotopic composition in surface snow and atmospheric vapor together with near-surface atmospheric turbulence and snow-air latent and sensible heat fluxes, obtained at the East Greenland Ice-Core Project drilling site in summer 2016. For two 4-day-long time periods, significant diurnal variations in atmospheric water isotopologues are observed. A model is developed to explore the impact of this variability on the surface snow isotopic composition. Our model suggests that the snow isotopic composition in the upper subcentimeter of the snow exhibits a diurnal variation with amplitudes in δ18O and δD of ~2.5‰ and ~13‰, respectively. As comparison, such changes correspond to 10-20% of the magnitude of seasonal changes in interior Greenland snow pack isotopes and of the change across a glacial-interglacial transition. Importantly, our observation and model results suggest, that sublimation-induced fractionation needs to be included in simulations of exchanges between the vapor and the snow surface on diurnal timescales during summer cloud-free conditions in northeast Greenland.

4.
J Hazard Mater ; 376: 37-47, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31121451

RESUMO

Poly-4-vinylpyridine grafted poly(vinylidene difluoride) (P4VP-g-PVDF) nanoporous polymer electrodes were found to be sensitive for Hg(II) analysis. The fabrication and characterization of functionalized nanoporous membrane-electrodes by FESEM and FTIR are presented. Functionalized nanopore charge state versus a large range of pH (1-10) was investigated by registering the streaming potential. This isoelectric point is achieved at the pKa of P4VP (pH = 5). Mercury adsorption at solid-liquid interface obeys a Langmuir law. A protocol for accurate Hg(II) analysis at ppb level was established. Calibration curves were performed and different real water samples (mineral water, ground water, surface water) were spiked and analyzed. The resulting sensor is intended to be integrated into existing systems or used standalone as portable devices. A first generation prototype exhibiting its own integrated potentiostat, its software and set of membrane-electrode pads is presented.

5.
Oncogene ; 35(27): 3587-97, 2016 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-26549034

RESUMO

Targeted therapies are effective in subsets of lung cancers with EGFR mutations and anaplastic lymphoma kinase (ALK) translocations. Large-scale genomics have recently expanded the lung cancer landscape with FGFR1 amplification found in 10-20% of squamous cell carcinomas (SCCs). However, the response rates have been low for biomarker-directed fibroblast growth factor receptor (FGFR) inhibitor therapy in SCC, which contrasts to the relatively high rates of response seen in EGFR mutant and ALK-translocated lung cancers treated with epidermal growth factor receptor (EGFR) inhibitors and ALK inhibitors, respectively. In order to better understand the low response rates of FGFR1-amplified lung cancers to FGFR inhibitors, relationships between gene copy number, mRNA expression and protein expression of FGFR1 were assessed in cell lines, tumor specimens and data from The Cancer Genome Atlas. The importance of these factors for the sensitivity to FGFR inhibitors was determined by analyzing drug screen data and conducting in vitro and in vivo experiments. We report that there was a discrepancy between FGFR1 amplification level and FGFR1 protein expression in a number of these cell lines, and the cancers with unexpectedly low FGFR1 expression were uniformly resistant to the different FGFR inhibitors. Further interrogation of the receptor tyrosine kinase activity in these discordant cell lines revealed co-activation of HER2 and platelet-derived growth factor receptor-α (PDGFRα) caused by gene amplification or ligand overexpression maintained phosphoinositide 3-kinase (PI3K) and MEK/ERK signaling even in the presence of FGFR inhibitor. Accordingly, co-inhibition of FGFR1 and HER2 or PDGFRα led to enhanced drug responses. In contrast, FGFR1-amplified high FGFR1 protein-expressing lung cancers are sensitive to FGFR inhibitor monotherapy by downregulating ERK signaling. Addition of a PI3K inhibitor to these high FGFR1 protein-expressing cancers further sensitized them to FGFR inhibitor. These data reveal that biomarker-directed trials for FGFR1-amplified SCC require assessment of FGFR1 protein expression and uncover novel therapeutic strategies for FGFR1-amplified SCC with low FGFR1 protein expression.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto , Antineoplásicos/farmacologia , Benzamidas/farmacologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Amplificação de Genes , Dosagem de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , Mesilato de Imatinib/farmacologia , Immunoblotting , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Compostos de Fenilureia/farmacologia , Piperazinas/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/genética , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
6.
HNO ; 63(2): 118-24, 2015 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-25608914

RESUMO

Surgical antibiotic prophylaxis (SAP) is defined as the administration of an antimicrobial agent prior to contamination in previously sterile spaces and fluid. SAP should not be confused with the therapeutic use of antibiotics. There are a growing number of studies with the goal of answering the question which patients benefit most from SAP during which specific surgical procedure. However, in the specific surgical field of head and neck surgery and otolaryngological surgery, there are only a few guidelines answering that question for specific procedures. The aim of this study was to analyze the evidence found in the literature and to develop a standard operating procedure, which specifically addresses head and neck and otolaryngeal surgical procedures.


Assuntos
Antibacterianos/administração & dosagem , Antibioticoprofilaxia/métodos , Infecções Bacterianas/etiologia , Infecções Bacterianas/prevenção & controle , Procedimentos Cirúrgicos Otorrinolaringológicos/efeitos adversos , Infecção da Ferida Cirúrgica/prevenção & controle , Humanos , Infecção da Ferida Cirúrgica/etiologia , Resultado do Tratamento
7.
J Clin Pharm Ther ; 39(3): 248-52, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24521180

RESUMO

WHAT IS KNOWN AND OBJECTIVES: Little is known about the ability of community pharmacists who are inexperienced in medication review to identify drug-related problems (DRPs). The objective of our study was to investigate the completeness of DRPs in terms of number, type and clinical relevance identified by community pharmacists when performing home medication reviews (HMRs). METHODS: This is a cross-sectional study within the intervention arm of a randomized controlled trial among community-dwelling patients (≥65 years, ≥5 drugs) in ten Dutch community pharmacies. Community pharmacists, who were inexperienced in medication review, received 2-day training in medication review. These pharmacists interviewed patients at home about their medicines, identified potential DRPs and made recommendations in combination with medication and clinical records. Expert reviewers completed the number of potential DRPs and recommendations by reviewing all available information, including patient interview reports. RESULTS AND DISCUSSION: In 155 patients, community pharmacists identified a mean of 3·6 (SD 2·8) potential DRPs per patient and expert reviewers added 6·5 (SD 3·2) DRPs. Community pharmacists formulated 2·6 (SD 2·3) recommendations per patient and reviewers added 7·5 (SD 3·3) recommendations. Community pharmacists identified a higher proportion of clinically relevant DRPs compared with expert reviewers, as assessed by DRPs with high priority [OR = 1·8 (95% CI 1·4-2·2)], DRPs associated with recommendations for drug change [OR = 1·9 (95% CI 1·5-2·3)] and implemented recommendations for drug change [OR = 2·1 (95% CI 1·6-2·7)]. WHAT IS NEW AND CONCLUSION: This study shows that the completeness of medication reviews by inexperienced community pharmacists with limited training could be improved, although they identified a higher proportion of potentially clinically relevant DRPs compared with expert reviewers. The results suggest that community pharmacists with limited experience in medication review may need more intensive post-graduate training.


Assuntos
Serviços Comunitários de Farmácia/organização & administração , Educação de Pacientes como Assunto/organização & administração , Medicamentos sob Prescrição/uso terapêutico , Papel Profissional , Idoso , Estudos Transversais , Feminino , Humanos , Capacitação em Serviço , Masculino , Países Baixos , Polimedicação , Medicamentos sob Prescrição/administração & dosagem , Medicamentos sob Prescrição/efeitos adversos
8.
J Clin Pharm Ther ; 37(6): 674-80, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22861493

RESUMO

WHAT IS KNOWN AND OBJECTIVE: To determine to what extent patient interviews contribute to the identification of drug-related problems (DRPs) in home medication reviews, in terms of number, type and clinical relevance. METHODS: We performed a cross-sectional study within the intervention arm of a randomized controlled trial. Patients were recruited from 10 Dutch community pharmacies. Patients were eligible if they were home-dwelling, aged 65 years and over and used five or more different drugs, including at least one cardiovascular or antidiabetic drug. The community pharmacist interviewed the patient at home about the medicines and identified potential DRPs in combination with medication and clinical records. This medication review was assessed and modified by an independent pharmacist reviewers' panel. Outcomes were the number and type of DRPs and recommendations and percentage of clinical relevant DRPs. Clinical relevance of DRPs was assessed by DRPs assigned a high priority, DRPs followed by recommendations for drug change and DRPs followed by implemented recommendations for drug change. RESULTS: A total of 1565 potential DRPs and recommendations (10 per patient).were identified for 155 patients (median age, 76 years; 54% women). Fifty-eight per cent of all recommendations involved a drug change; 27% of all DRPs were identified during patient interviews and 74% from medication and clinical records. Compared to DRPs identified from patient medication and clinical records, DRPs identified during patient interviews were more frequently assigned a high priority (OR = 1.8 [1.4-2.2]), were more frequently associated with recommendations for drug change (OR = 2.4 [1.9-3.1]) and were implemented recommendations for drug change (OR = 2.8 [2.1-3.7]). WHAT IS NEW AND CONCLUSION: This study shows that more than a quarter of all DRPs were identified during patient interviews. DRPs identified during patient interviews were more frequently assigned a higher clinical relevance.


Assuntos
Revisão de Uso de Medicamentos/métodos , Serviços de Assistência Domiciliar/organização & administração , Entrevistas como Assunto , Medicamentos sob Prescrição/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Serviços Comunitários de Farmácia/organização & administração , Estudos Transversais , Feminino , Humanos , Masculino , Países Baixos , Farmacêuticos/organização & administração , Polimedicação , Medicamentos sob Prescrição/uso terapêutico , Papel Profissional
9.
Hautarzt ; 63(8): 648-52, 2012 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-22406762

RESUMO

A 28-month-old boy developed a cutaneous and subcutaneous lesion of the scalp together with alopecia. Treatment with sulfadiazine silver ointment and oral administration of cefaclor failed. The boy lived on a farm where cows and calves were present. He presented with a 5 cm erythematous, erosive, edematous, and sharply defined lesion with yellow crusts and circumscribed alopecia on the temporoparietal scalp. Peripheral hairs were easily epilated. Swabs from the wound revealed cMRSA (community acquired methicillin-resistant Staphylococcus aureus, Panton Valentine Leukocidin [PVL] toxin negative). There was no improvement after treatment with cefuroxime intravenously over 3 days. Therapy was changed to vancomycin and fosfomycin. Because of the purulent abscess, surgical incision was performed. PCR (polymerase chain reaction)-Elisa assay detected Trichophyton (T.) interdigitale-DNA from wound secretion and skin biopsy. Because of the clinical and molecular diagnosis of tinea capitis, oral antifungal therapy with fluconazole 5 mg kg(-1) body weight was started, along with cotrimoxazole and fosfomycin for the cMRSA. After 4 weeks incubation, the causative agent T. verrucosum was grown on culture and its identity confirmed by sequencing of the "internal transcribed spacer" (ITS) region of the ribosomal DNA. After 4 weeks of fluconazole, the lesion was nearly healed.


Assuntos
Fluconazol/uso terapêutico , Dermatoses do Couro Cabeludo/diagnóstico , Dermatoses do Couro Cabeludo/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/diagnóstico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Tinha do Couro Cabeludo/diagnóstico , Tinha do Couro Cabeludo/tratamento farmacológico , Antifúngicos/uso terapêutico , Pré-Escolar , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina , Resultado do Tratamento
10.
Nutr Cancer ; 64(3): 377-85, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22332933

RESUMO

Complementary and alternative medicine (CAM) represents a wide range of treatment modalities. CAM products may interact with enzymes, transport proteins, and may therefore influence drug metabolism. The prevalence and patterns of CAM usage among patients with head and neck carcinoma (HNC) are largely unknown. This cross-sectional study was designed to document pattern of CAM consumption in patients with HNC. Statistical differences in a significantly higher prevalence of CAM consumption between tumor patients (n = 107) and the control group (n = 112) could be detected. Concerning the frequency of CAM usage, we could document a significant increased consumption of CAM among tumor patients (42.8% vs. 62.6%) especially for herbal teas (P < 0.05), phytotherapy (P < 0.001), supplement products (P < 0.05), and "other" supplements (P < 0.005) comparing the controls. Furthermore a significant influence of female gender and an increased CAM usage could be illustrated. Concerning the knowledge of potential interactions of CAM consumption, only 6.25% of the controls and 19.6% of tumor patients know about possible side effects but only 1.7% of the controls and 6.5% of the tumor patients informed their physician about the CAM usage. The frequency of CAM in head and neck tumor patients seems to be relevant in the supervision of anticancer therapies.


Assuntos
Terapias Complementares/métodos , Suplementos Nutricionais , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Fitoterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Estudos Transversais , Feminino , Alemanha , Humanos , Masculino , Micronutrientes/administração & dosagem , Pessoa de Meia-Idade , Projetos Piloto , Prevalência , Inquéritos e Questionários , Adulto Jovem
11.
Oncol Rep ; 27(1): 270-80, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21993766

RESUMO

The most common neoplasm arising in the upper aerodigestive tract is head and neck squamous cell carcinoma (HNSCC). Tumor growth, invasion and systemic dissemination is a multistep process of dysregulated cellular signaling pathways and an altered cell-cell and cell-matrix interaction. Aberrant Wnt/ß-catenin signaling is linked to tumor development and dissemination in several tumor entities. ß-catenin is a multifunctional protein within the canonical Wnt pathway, which is an important factor for reducing cell-cell adhesion in malignant tissue and for triggering cell cycle progression and unscheduled proliferation. Another pivotal factor in carcinogenesis is the tyrosine kinase receptor c-kit, which in the case of dysregulated expression is associated with neoplastic transformation in epithelial tissue. This study evaluates the expression pattern of secreted and nuclear ß-catenin and c-kit in p16-positive and HPV-negative squamous cell carcinomas (SCC) and the vulnerability of therapy with the tyrosine kinase inhibitor imatinib as a potential targeted treatment modality compared to platinum-based chemotherapeutic drugs. The different squamous tumor cell lines were incubated with increasing concentrations of carboplatin (3 or 7.5 µmol/ml) and imatinib (18 or 30 µmol/ml). ELISA and immunohistochemical methods were carried out after 48, 72, 120, 192 and 240 h. We detected a reliable trend towards significantly decreased cytosolic and nuclear ß-catenin and c-kit expression levels in p16-positive SCC and non-HPV HNSCC cells induced by imatinib exposure for an extended incubation period, whereas platinum-based agents had no or, at best, a slight influence. Virus-transformed squamous cell carcinoma (CERV196) cells were characterized by a reduced susceptibility to an imatinib-altered ß-catenin expression. Further studies are planned to investigate this observance in HPV-positive HNSCC in vitro. The implementation of a selective molecular therapy in established chemotherapeutic regimes may enhance the efficacy of platinum-based chemotherapy without increased toxicity and could thus improve the clinical outcome in HNSCC, irrespective of the HPV status.


Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Piperazinas/farmacologia , Pirimidinas/farmacologia , Fator de Células-Tronco/biossíntese , beta Catenina/biossíntese , Benzamidas , Western Blotting , Carcinoma de Células Escamosas/virologia , Linhagem Celular Tumoral , Ensaio de Imunoadsorção Enzimática , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Mesilato de Imatinib , Imuno-Histoquímica , Técnicas In Vitro , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas do Core Viral/metabolismo
12.
Occup Med (Lond) ; 62(1): 41-6, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22016340

RESUMO

BACKGROUND: High muscle strength is considered relevant for preventing musculoskeletal disorders and long-term sickness absence. However, prospective studies on the association between muscle strength and future musculoskeletal disorders and long-term sickness absence are few and show contrasting results. AIMS: To investigate the association between low muscle strength and future musculoskeletal disorders and long-term sickness absence. METHODS: Muscle strength in trunk flexion and extension, shoulder elevation and abduction as well as handgrip was recorded from a representative sample of Danish workers (n = 421) in 1995. Musculoskeletal disorders were reported 5 years later (in 2000). Information on long-term sickness absence was retrieved from a register of social transfer payments in the period 1996-2007. RESULTS: Regression analyses adjusted for age, gender, smoking, body mass index and physical work demands showed that workers with low muscle strength (the lowest quartile) of trunk extension and flexion, shoulder elevation and abduction and handgrip did not have a significantly increased risk for future musculoskeletal disorders or long term sickness absence compared with stronger workers. CONCLUSIONS: Low muscle strength does not seem to be a good predictor for musculoskeletal disorders and long-term sickness absence in the general working population.


Assuntos
Absenteísmo , Força Muscular/fisiologia , Doenças Musculoesqueléticas/epidemiologia , Dor/epidemiologia , Licença Médica/estatística & dados numéricos , Adulto , Dinamarca/epidemiologia , Feminino , Seguimentos , Mãos/fisiopatologia , Humanos , Dor Lombar/epidemiologia , Masculino , Estudos Prospectivos , Medição de Risco , Dor de Ombro/epidemiologia , Tronco/fisiopatologia
13.
Oncol Rep ; 26(5): 1099-109, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21805039

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy known to be the most common neoplasm appearing in the upper aerodigestive tract. The poor five-year survival rate has remained unchanged in the last decades despite the emergence of improved techniques in surgery, radiation and chemotherapy. In the last 20 years awareness of a subset of squamous cell carcinomas induced by oncogenic forms of the human papilloma virus (HPV) (high-risk types 16 and 18) has increased. The incidence of HPV-associated oropharyngeal cancer is rising, indicating the increased importance of the viral etiology. Cell proliferation, migration, induction of tumor vascularization and carcinogenesis, as well as invasion facilitation is regulated by a variety of angiogenic peptides like PDGF, PDGF-R and VEGF. They might be an encouraging target for biological anticancer therapy by inhibiting disrupted cellular signaling pathways. Imatinib has been shown to target specific tyrosine kinases, inhibiting proliferation in various cancer entities. The purpose of this study was to evaluate the expression pattern of angiogenic factors (VEGF, PDGF and PDGF-R) in HPV-positive (p16-CERV196 SCC) and (-negative squamous cell carcinoma (HNSCC). The study also evaluated the vulnerability of anti-angiogenesis therapy depending on the HPV status as potential treatment modality compared to established platinum-based chemotherapeutic drugs. The different squamous tumor cell lines were incubated with increasing concentrations of carboplatin (3 and 7.5 µmol) and imatinib (18 and 30 µmol). ELISA immunohistochemical methods were carried out after 48, 72, 120, 192 and 240 h. We demonstrated a significant reduction of VEGF and PDGF-Rα/ß expression patterns after incubation of imatinib in ELISA and immunohistochemical methods, irrespective of the HPV status of the tumor cells, whereas the application of carboplatin had no impact on the expression of angiogenic peptides. Viral oncogen-transformed squamous cell carcinoma (CERV196) cells were characterized by a reduced susceptibility for an imatinib-altered VEGF expression. Further studies are planned to investigate this observance in HPV-positive HNSCC in vitro. The implementation of a selective molecular anti-angiogenic therapy in established chemotherapeutic regimens may enhance the efficacy of platinum-based chemotherapy without an increased toxicity profile and could thus improve the clinical outcome in HNSCC, irrespective of the HPV status.


Assuntos
Proteínas Angiogênicas/biossíntese , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/virologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/virologia , Infecções por Papillomavirus/metabolismo , Piperazinas/farmacologia , Pirimidinas/farmacologia , Adulto , Antineoplásicos/farmacologia , Benzamidas , Carboplatina/farmacologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Transformação Celular Viral , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Papillomavirus Humano 16/fisiologia , Humanos , Mesilato de Imatinib , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/patologia , Fator de Crescimento Derivado de Plaquetas/biossíntese , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/biossíntese , Receptor beta de Fator de Crescimento Derivado de Plaquetas/biossíntese , Fator A de Crescimento do Endotélio Vascular/biossíntese
14.
Int J Oncol ; 38(4): 1001-12, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21249316

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy. The development of new treatment modalities in order to improve long-term survival of patients with HNSCC is imperative. Numerous studies have demonstrated that carcinogenesis and tumor cell dissemination is influenced by the tumor microenvironment. The protein-kinase-receptors (PTKs) are essential elements of the intracellular signal transduction pathway and regulate cell growth, development and apoptosis. Cell proliferation, migration, induction of tumor vascularization and carcinogenesis, invasion is regulated by a variety of angiogenic factors, such as PDGF (platelet-derived growth factor), VEGF (vascular endothelial growth factor) and their respective tyrosine kinase receptors (PDGF-R and VEGF-R). They present promising targets for anti-cancer therapy through abrogation of impaired signaling pathways. Indeed, imatinib, a small molecule drug targeting these protein kinases, has antiproliferative effects in several cancer types. The purpose of this study was to investigate the potential synergism of imatinib and carboplatin on the expression of PDGF, PDGF-R α/ß and VEGF in different HNSCC cell lines. Several tumor cell lines were subjected to increasing concentrations of carboplatin (3 and 7.5 µmol/l) and imatinib (18 and 30 µmol/l) and ELISA, immunohistochemical methods and RQ-PRC after 48, 72, 120 and 240 h were used to assess their expression levels. While PDGF-Rα/ß expression was unimpaired at lower imatinib concentrations (18 µmol/l), PDGF-Rα/ß expression was suppressed at 30 µmol/l, and suppression was enhanced by the presence of carboplatin. By RQ-PCR, a significant reduction of PDGF-Rα/ß expression was detected (p<0.5). We observed explicit significant reduction in VEGF levels with increasing concentrations of imatinib and with the combination of the two chemotherapeutic drugs (p<0.5). We report for the first time evidence of synergism of imatinib and carboplatin in suppressing VEGF, PDGF and PDGF-Rα/ß expression in HNSCC.


Assuntos
Antineoplásicos/farmacologia , Carboplatina/farmacologia , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Piperazinas/farmacologia , Fator de Crescimento Derivado de Plaquetas/metabolismo , Pirimidinas/farmacologia , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Benzamidas , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Mesilato de Imatinib , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Transcrição Gênica
15.
Int J Nurs Stud ; 48(1): 47-55, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21195815

RESUMO

BACKGROUND: Pain and anxiety are a common problem in all recovery phases after a burn. The Burns Specific Pain Anxiety Scale (BSPAS) was proposed to assess anxiety in burn patients related to painful procedures. OBJECTIVES: To assess internal consistency, discriminative construct validity, dimensionality and convergent construct validity of the Brazilian-Portuguese version of the Burns Specific Pain Anxiety Scale. DESIGN: In this cross-sectional study, the original version of the BSPAS, adapted into Brazilian Portuguese, was tested for internal consistency (Cronbach's Alpha), discriminative validity (related to total body surface area burned and sex), dimensionality (through factor analysis), and convergent construct validity (applying the Visual Analogue Scale for pain and State-Anxiety-STAI) in a group of 91 adult burn patients. RESULTS: The adapted version of the BSPAS displayed a moderate and positive correlation with pain assessments: immediately before baths and dressings (r=0.32; p<0.001), immediately after baths and dressings (r=0.31; p<0.001) and during the relaxation period (r=0.31; p<0.001) and with anxiety assessments (r=0.34; p<0.001). No statistically significant differences were observed when comparing the mean of the adapted version of the BSPAS scores with sex (p=0.194) and total body surface area burned (p=0.162) (discriminative validity). The principal components analysis applied to our sample seems to confirm anxiety as one single domain of the Brazilian-Portuguese version of the BSPAS. Cronbach's Alpha showed high internal consistency of the adapted version of the scale (0.90). CONCLUSION: The Brazilian-Portuguese version of the BSPAS 9-items has shown statically acceptable levels of reliability and validity for pain-related anxiety evaluation in burn patients. This scale can be used to assess nursing interventions aimed at decreasing pain and anxiety related to the performance of painful procedures.


Assuntos
Ansiedade/diagnóstico , Queimaduras/complicações , Avaliação em Enfermagem/métodos , Dor/complicações , Índice de Gravidade de Doença , Inquéritos e Questionários/normas , Adolescente , Adulto , Idoso , Ansiedade/etiologia , Brasil , Estudos Transversais , Análise Discriminante , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa em Avaliação de Enfermagem , Medição da Dor , Análise de Componente Principal , Psicometria , Tradução
16.
Oncol Rep ; 24(5): 1213-6, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20878112

RESUMO

Squamous cell carcinoma of the head and neck (SCCHN) presents at a locally advanced (LA) stage in many patients. Chemotherapy, which is one fundamental therapy mode for local disease control of inoperable disease or if organ preservation is desired, has become an important factor of first line treatment regimens either during or prior to radiotherapy (RT). Patients with locoregionally advanced inoperable, recurrent or metastatic disease still have a poor prognosis, which enforces the need for new treatment approaches and new drug therapies, adjusted to the different settings of the disease. One innovative progress for this collective of patients with locally advanced tumor was the implementation of Docetaxel in chemotherapeutic regimes in optimal combination with concurrent chemoradiotherapy or in neoadjuvant setting of induction phase treatment. Docetaxel combined with the conventional chemotherapy regimen, containing Cisplatin and 5-Fluorouracil (TPF), is now acknowledged as being the gold standard of induction treatment. Various studies suggest survival advantage due to the induction chemotherapy (ICT) followed by chemoradiotherapy, which is known as sequential therapy, over chemoradiotherapy alone. In contrast to prevailing studies we administered Docetaxel, Carboplatin and 5-FU within the frame-work of induction chemotherapy instead of conventional use of Cisplatin for five patients with locoregionally advanced HNSCC. The clinical progress was evaluated through cross section imaging (computer tomography/MRI) prior and after ICT and classified following the RECIST criteria. Due to a very small collective of patient and the administration of Carboplatin instead of Cisplatin in this study, it was not possible to document the the efficacy of ICT (TPF) concerning survival advantage in patient with locoregionally advanced head and neck tumors. Further studies with an extended collective of patients are neccessary.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Cisplatino , Docetaxel , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Taxoides/administração & dosagem , Taxoides/efeitos adversos
17.
Burns ; 34(6): 775-82, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18375068

RESUMO

An assessment carried out on adolescents aged 11-18 who had suffered severe burns in early childhood 10-11 years previously indicated that the levels of problem behavior were similar and the levels of depression lower than those reported by adolescents in comparable reference populations. Adolescents' self-reports revealed higher levels of the personality traits emotional stability, agreeableness and extraversion. Self-reports further revealed lower levels of passive coping than are found in a normative reference population. Regression analyses showed that less emotional stability, less agreeableness and more passive coping styles were related to increased behavioral problems and symptoms of depression. The authors argue that future studies should focus on resilience and within-group differences.


Assuntos
Adaptação Psicológica , Queimaduras/psicologia , Transtornos do Comportamento Infantil/psicologia , Personalidade , Inquéritos e Questionários , Adolescente , Criança , Transtornos do Comportamento Infantil/diagnóstico , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Análise de Regressão , Autoimagem , Fatores de Tempo
18.
Burns ; 34(4): 433-40, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18207643

RESUMO

Treatment of people with burn injuries includes recovery of optimal function for survivors to fully participate in society, psychologically and physically. Increased likelihood of physical survival has led to greater concern for potential psychological morbidity for the burn survivor. Based on research and on many years of clinical experience in providing psychosocial care to burned children and adults, the authors outline their approach to assisting burn survivors and their families through the arduous process of recovery from admission through critical care, inpatient recuperation and reintegration upon hospital discharge. A philosophy of rehabilitation, a process that may occur for many months or years after patients' discharge from their acute hospitalization, is presented in the form of seven guidelines for working with burn survivors.


Assuntos
Adaptação Psicológica , Queimaduras/reabilitação , Cuidados Críticos , Recuperação de Função Fisiológica , Atividades Cotidianas , Adulto , Queimaduras/psicologia , Criança , Cuidados Críticos/organização & administração , Cultura , Atenção à Saúde/normas , Hospitalização/estatística & dados numéricos , Humanos , Avaliação de Resultados em Cuidados de Saúde , Alta do Paciente/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Qualidade de Vida
19.
Br J Dermatol ; 158(1): 95-100, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17986307

RESUMO

BACKGROUND: Itching (pruritus) following burns is a well-known clinical problem. However, there are no long-term prospective studies that document the course and the extent of the problem. Studies on risk factors are anecdotal. OBJECTIVES: To study self-reported itching in a multicentre cohort among adults with burns at 3, 12 and 24 months postburn. Further, to examine psychological and injury characteristics in relation to itching at these three points in time. METHODS: Itching was assessed as part of a self-report scar complaint list in a prospective longitudinal cohort study. Injury characteristics, demographics and self-reported post-traumatic stress symptoms were examined as possible risk factors in three linear regression models. RESULTS: A total of 510 persons participated. The reported prevalence rates of mild to severe itching were as high as 87%, 70% and 67% at the three respective points in time. Significant predictors of itching at all three points in time were deep dermal injury and early post-traumatic stress symptoms. Along with these, total burned surface area and female gender were predictors at 3 months postburn. CONCLUSIONS: Itching remains a significant problem over a 2-year period. Individuals having undergone surgical procedures and experiencing early post-traumatic distress are more likely to suffer from long-term and persistent itching. Implications regarding practice and research are discussed.


Assuntos
Queimaduras/complicações , Prurido/etiologia , Adolescente , Adulto , Idoso , Bélgica/epidemiologia , Queimaduras/epidemiologia , Queimaduras/cirurgia , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prurido/epidemiologia , Índice de Gravidade de Doença , Fatores Sexuais , Transtornos de Estresse Pós-Traumáticos/complicações
20.
Int J Med Robot ; 3(2): 135-9, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17619243

RESUMO

BACKGROUND: A robotic system for the implantation of a total hip arthroplasty (THA) is currently under development. One of the goals of this system is non-invasive patient fixation, aiding the robotic system by an infrared tracking system. To determine the extent of fixation that can be achieved by non-invasive methods, an in vitro study was performed. METHODS: In cadaver testing, different non-invasive fixation methods (Arthrex leg holder with tourniquet mechanism; arthroscopic leg holder with disposable foam inserts; gynaecological leg holder; Goepel knee crutch) were evaluated under load in different directions. RESULTS: Deviation was measured in the range 0.33-18.1 mm with up to 20 N load. The testing showed the pneumatic leg holder system to provide the highest stability, followed by an arthroscopic leg holder system with foam inserts. CONCLUSIONS: Use of a leg holder with foam inserts produced a stability that should enable tracking of the remaining deviation by the navigation system. We will therefore use this method in our future development of the robotic milling tool.


Assuntos
Artroplastia de Quadril/instrumentação , Artroplastia de Quadril/métodos , Artroscopia/métodos , Robótica , Idoso , Cadáver , Desenho de Equipamento , Humanos , Raios Infravermelhos , Masculino , Movimento , Postura , Ajuste de Prótese , Cirurgia Assistida por Computador
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