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1.
J Interprof Care ; 35(6): 899-906, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33190512

RESUMO

The goal of health professional education programs is to produce competent graduates, with an ability to work collaboratively as effective healthcare team members. We explored the reflections of students and clinical facilitators, in response to participation in a structured interprofessional education (IPE) clinical placement program. In our qualitative study we used an exploratory case study design. In our analysis, we highlight the benefits of interprofessional practice. Key themes identified by students included: limited opportunities to engage in IPE across their course; lack of clarity around IPE; value of IPE for students, practitioners, and patient outcomes; and need for IPE opportunities to be integrated into placements. Key themes identified by the clinical facilitators included: being reminded of the value of IPE for students and patients; preparation for IPE placements need to be embedded in curricula; coordination and communication of IPE learning activities need to be clear for staff and students; and IPE should continue as part of the broader clinical education agenda. Our findings reinforce the notion that students and clinical facilitators value the importance of IPE for student learning within the clinical placement setting. The outcomes offer valuable insights for universities and hospital and health care contexts for setting up and implementing IPE activities, and we provide recommendations for improving ongoing IPE efforts within clinical placement setting.


Assuntos
Educação Interprofissional , Relações Interprofissionais , Atenção à Saúde , Humanos , Equipe de Assistência ao Paciente , Pesquisa Qualitativa
2.
Bull Exp Biol Med ; 166(5): 656-660, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30903492

RESUMO

One of actively developing trends in modern pharmacology is the use of the transcriptome analysis for drug repositioning. We have previously detected two molecular markers of relapses in patients with malignant breast tumors: ELOVL5 and IGFBP6. Poor prognosis is associated with low expression of these markers. Here we analyze the effects of simvastatin and a new potential proteasome inhibitor K7174 inducing expression of IGFBP6 and EVOVL5 on the proliferation of breast cancer cells MDA-MB-231 and DU4475. Compound K7174 potentiates the inhibitory effect of simvastatin on the proliferation of DU4475 cells characterized by low expression of ELOVL5-IGFBP6 pair, but not on the proliferation of MDA-MB-231 cells with high expression of these markers.


Assuntos
Neoplasias da Mama/microbiologia , Acetiltransferases/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Combinação de Medicamentos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Elongases de Ácidos Graxos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Recidiva Local de Neoplasia , Sinvastatina/farmacologia , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética
3.
Bull Exp Biol Med ; 164(5): 650-654, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29577195

RESUMO

Protein IGFBP6 plays an important role in the pathogenesis of many malignant tumors, including breast cancer. The relationship between IGFBP6 protein and the expression of genes associated with the epithelial-mesenchymal transition is studied. Gene IGFBP6 knockdown does not trigger the epithelial-mesenchymal transition in MDA-MB-231 cells, but modifies significantly the expression of many genes involved in this process. A decrease of IGFBP6 expression can involve a decrease in the expression of N-cadherin and transcription factor Slug.


Assuntos
Neoplasias da Mama/metabolismo , Caderinas/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Proteína 6 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Neoplasias da Mama/genética , Caderinas/genética , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Proteína 6 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Modelos Biológicos
4.
Bull Exp Biol Med ; 164(5): 688-692, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29582205

RESUMO

IGFBP6 gene plays an important role in the pathogenesis of breast cancer. In this work, we performed knockdown of IGFBP6 gene in MDA-MB-231 cells and obtained a stable cell line. Knockdown of IGFBP6 gene was confirmed by the real-time PCR. The influence of IGFBP6 gene on migration and proliferation of breast cancer cells was studied. Knockdown of IGFBP6 gene reduced migration activity of MDA-MB-231 cells and increased their proliferation rate. This in vitro cell model can be used for the further analysis of the role of IGFBP6 gene in the pathogenesis of breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Movimento Celular/fisiologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Reação em Cadeia da Polimerase em Tempo Real
5.
Eur Radiol ; 27(2): 790-800, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27169574

RESUMO

PURPOSE: To compare multidetector computed tomography (MDCT) and cone-beam computed tomography (CBCT) regarding radiation, resolution, image noise, and image quality. METHODS: CBCT and 256-MDCT were compared based on three scan protocols: Standard-dose (≈24 mGy), reduced-dose (≈9 mGy), and low-dose (≈4 mGy). MDCT images were acquired in standard- and high-resolution mode (HR-MDCT) and reconstructed using filtered back projection (FBP) and iterative reconstruction (IR). Spatial resolution in linepairs (lp) and objective image noise (OIN) were assessed using dedicated phantoms. Image quality was assessed in scans of 25 cadaver heads using a Likert scale. RESULTS: OIN was markedly higher in FBP-MDCT when compared to CBCT. IR lowered the OIN to comparable values in standard-mode MDCT only. CBCT provided a resolution of 13 lp/cm at standard-dose and 11 lp/cm at reduced-dose vs. 11 lp/cm and 10 lp/cm in HR-MDCT. Resolution of 10 lp/cm was observed for both devices using low-dose settings. Quality scores of MDCT and CBCT did not differ at standard-dose (CBCT, 3.4; MDCT, 3.3-3.5; p > 0.05). Using reduced- and low-dose protocols, CBCT was superior (reduced-dose, 3.2 vs. 2.8; low dose, 3.0 vs. 2.3; p < 0.001). CONCLUSION: Using the low-dose protocol, the assessed CBCT provided better objective and subjective image quality and equality in resolution. Similar image quality, but better resolution using CBCT was observed at higher exposure settings. KEY POINTS: • The assessed CBCT device provided better image quality at lower doses. • Objective and subjective image quality were comparable using higher exposure settings. • CBCT showed superior spatial resolution in standard-dose and reduced-dose settings. • Modern noise-reducing tools are used in CBCT devices currently. • MDCT should be preferred for assessment of soft-tissue injuries and oncologic imaging.


Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Face/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Cadáver , Cabeça/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Imagens de Fantasmas , Estudos Prospectivos , Doses de Radiação , Radiometria
6.
Bull Exp Biol Med ; 160(6): 807-10, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27165065

RESUMO

Molecule L1CAM is specific for nerve cells and tumors of various localizations. The expression of L1CAM is significantly higher in melanoma in comparison with benign nevi and correlates with the progress of melanoma and transition from radial to vertical growth. Monoclonal antibodies to L1CAM effectively and specifically attenuate melanoma growth, though stimulates the epithelial-mesenchymal transition. shRNA-mediated knock-down of L1CAM showed the involvement of L1CAM in regulation of activity of the canonical Wnt pathway and expression of genes of class I melanoma-associated antigens (MAGE).


Assuntos
Antígenos de Neoplasias/genética , Proteínas de Neoplasias/genética , Molécula L1 de Adesão de Célula Nervosa/fisiologia , Via de Sinalização Wnt , Antígenos de Neoplasias/metabolismo , Linhagem Celular Tumoral , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Melanoma/genética , Melanoma/metabolismo , Proteínas de Neoplasias/metabolismo
7.
Br J Cancer ; 110(3): 753-63, 2014 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-24322891

RESUMO

BACKGROUND: C-Fos was initially described as oncogene, but was associated with favourable prognosis in ovarian cancer (OvCa) patients. The molecular and functional aspects underlying this effect are still unknown. METHODS: Using stable transfectants of SKOV3 and OVCAR8 cells, proliferation, migration, invasion and apoptotic potential of c-FOS-overexpressing clones and controls were compared. Adherence to components of the extracellular matrix was analysed in static assays, and adhesion to E-selectin, endothelial and mesothelial cells in dynamic flow assays. The effect of c-FOS in vivo was studied after intraperitoneal injection of SKOV3 clones into SCID mice, and changes in gene expression were determined by microarray analysis. RESULTS: Tumour growth after injection into SCID mice was strongly delayed by c-FOS overexpression, with reduction of lung metastases and circulating tumour cells. In vitro, c-FOS had only weak influence on proliferation and migration, but was strongly pro-apoptotic. Adhesion to components of the extracellular matrix (collagen I, IV) and to E-selectin, endothelial and mesothelial cells was significantly reduced in c-FOS-overexpressing OvCa cells. This corresponds to deregulation of adhesion proteins and glycosylation enzymes in microarray analysis. CONCLUSION: In addition to its known pro-apoptotic effect, c-FOS might influence OvCa progression by changing the adhesion of OvCa cells to peritoneal surfaces.


Assuntos
Carcinogênese/metabolismo , Adesão Celular/genética , Neoplasias Ovarianas/genética , Proteínas Proto-Oncogênicas c-fos/genética , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Progressão da Doença , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Invasividade Neoplásica/genética , Células Neoplásicas Circulantes/metabolismo , Neoplasias Ovarianas/patologia , Proteínas Proto-Oncogênicas c-fos/biossíntese
8.
Br J Cancer ; 109(7): 1848-58, 2013 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-24022195

RESUMO

BACKGROUND: The Coxsackie- and Adenovirus Receptor (CAR) has been assigned two crucial attributes in carcinomas: (a) involvement in the regulation of growth and dissemination and (b) binding for potentially therapeutic adenoviruses. However, data on CAR expression in cancer types are conflicting and several entities have not been analysed to date. METHODS: The expression of CAR was assessed by immunohistochemical staining of tissue microarrays (TMA) containing 3714 specimens derived from 100 malignancies and from 273 normal control tissues. RESULTS: The expression of CAR was detected in all normal organs, except in the brain. Expression levels, however, displayed a broad range from being barely detectable (for example, in the thymus) to high abundance expression (for example, in the liver and gastric mucosa). In malignancies, a high degree of variability was notable also, ranging from significantly elevated CAR expression (for example, in early stages of malignant transformation and several tumours of the female reproductive system) to decreased CAR expression (for example, in colon and prostate cancer types). CONCLUSION: Our results provide a comprehensive insight into CAR expression in neoplasms and indicate that CAR may offer a valuable target for adenovirus-based therapy in a subset of carcinomas. Furthermore, these data suggest that CAR may contribute to carcinogenesis in an entity-dependent manner.


Assuntos
Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus/metabolismo , Neoplasias/metabolismo , Infecções por Adenoviridae , Transformação Celular Neoplásica/genética , Infecções por Coxsackievirus , Regulação Neoplásica da Expressão Gênica , Humanos , Análise Serial de Proteínas
9.
Eur J Clin Microbiol Infect Dis ; 31(2): 207-15, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21604096

RESUMO

Pseudomonas aeruginosa (PA) can cause infections in compromised hosts by interacting with the glycocalyx of host epithelial cells. It binds to glycostructures on mucosal surfaces via two lectins, which are carbohydrate-binding proteins, named PA-IL and PA-IIL, and blocking this interaction is, thus, an attractive anti-adhesive strategy. The aim of this study was to determine by ciliary beat frequency (CBF) analysis whether monosaccharides or peptides mimicking glycostructures represent blockers of PA lectin binding to human airway cilia. The treatment with monosaccharides and peptides alone did not change the CBF compared to controls and the tested compounds did not influence the cell morphology or survival, with the exception of peptide pOM3. PA-IL caused a decrease of the CBF within 24 h. D-galactose as well as the peptides mimicking HNK-1, polysialic acid and fucose compensated the CBF-modulating effect of PA-IL with different affinities. PA-IIL also bound to the human airway cilia in cell culture and resulted in a decrease of the CBF within 24 h. L(-)-fucose and pHNK-1 blocked the CBF-decreasing effect of PA-IIL. The HNK-1-specific glycomimetic peptide had a high affinity for binding to both PA-IL and PA-IIL, and inhibited the ciliotoxic effect of both lectins, thus, making it a strong candidate for a therapeutic anti-adhesive drug.


Assuntos
Cílios/efeitos dos fármacos , Lectinas/antagonistas & inibidores , Monossacarídeos/farmacologia , Peptídeos/farmacologia , Pseudomonas aeruginosa/metabolismo , Adesinas Bacterianas/metabolismo , Sequência de Aminoácidos , Aderência Bacteriana/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Brônquios/metabolismo , Brônquios/microbiologia , Antígenos CD57/química , Antígenos CD57/metabolismo , Cílios/metabolismo , Fucose/química , Fucose/metabolismo , Galactose/química , Galactose/metabolismo , Humanos , Lectinas/metabolismo , Mimetismo Molecular , Dados de Sequência Molecular , Peptídeos/química , Pseudomonas aeruginosa/patogenicidade
10.
Z Gastroenterol ; 49(3): 335-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21391164

RESUMO

BACKGROUND AND AIMS: Parenteral nutrition is life-saving for patients with severe intestinal failure. Line-related blood stream infection is the most frequent complication and strategies have been developed to sterilize central lines. Nevertheless, failures of attempted sterilization are not well understood. METHODS: 19 ports were explanted from 19 patients receiving parenteral nutrition because of port-related blood stream infection and failed sterilization, defined as a) recurrence of the same organism after a recent sterilization attempt <90 days), b) recovery of the causative organism after 10 days of proper antibiotic therapy or c) insufficient clinical improvement. Port chambers were opened and swabs were examined by culture. RESULTS: Pathogens resembled those typically found in successfully treated line-related blood stream infection. Despite proper therapy for a median of 6.5 days the same pathogen was recovered from 18/19 chambers. In 9/19 chambers visible debris were found, from which the pathogen could be cultured. CONCLUSIONS: Infected debris or infected biofilms in the chamber are the reason for failure to sterilize a port. Lock techniques, single lumen tunneled catheters or in certain settings the exchange of only the port chamber may be approaches to prevent, circumvent or treat failures of attempted sterilization of an infected port system.


Assuntos
Infecções Bacterianas/etiologia , Infecções Bacterianas/microbiologia , Enteropatias/complicações , Enteropatias/enfermagem , Nutrição Parenteral/efeitos adversos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
Br J Cancer ; 102(3): 602-9, 2010 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-20010946

RESUMO

BACKGROUND: Interactions of endothelial selectins with tumour cell glycoconjugates have been shown to have a major role in tumour cell dissemination in previous experiments. However, experiments validating this observation were limited in value, as 'metastases' in these experiments were artificially induced by i.v. injection rather than developed spontaneously as in true metastases. METHODS: Endothelial (E) and platelet (P)-selectin-deficient severe combined immunodeficient (scid) mice were generated and human HT 29 colon cancer cells were subcutaneously inoculated in these mice and in wild-type scid mice. Tumour growth, spontaneous metastasis formation in the lung and adherence of HT29 cells to E- and P-selectin under flow were determined. RESULTS: The number of metastases decreased by 84% in E- and P-selectin-deficient scid mice, compared with wild-type scid mice. The remaining 16% metastases in the E- and P-selectin-deficient scid mice grew within the pulmonary artery and not in the alveolar septae as they did in wild-type scid mice. Flow experiments indicate that tumour cells roll and tether on an E- and P-selectin matrix similar to leukocytes; however, firm adhesion is mainly mediated in E-selectin. CONCLUSION: Our results indicate that E- and P-selectins have a crucial role in spontaneous metastasis formation. As the human HT 29 colon cancer cells are positive for the lectin Helix pomatia agglutinin (HPA), which identified the metastatic phenotype in earlier clinical studies, these results are of particular clinical relevance.


Assuntos
Neoplasias do Colo/patologia , Selectina E/fisiologia , Neoplasias Pulmonares/secundário , Selectina-P/fisiologia , Animais , Adesão Celular , Células HT29 , Humanos , Lectinas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Células Neoplásicas Circulantes , Oligossacarídeos/análise , Selectina-P/análise , Antígeno Sialil Lewis X
12.
Ann Rheum Dis ; 68(6): 1067-71, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19028765

RESUMO

OBJECTIVE: The pathogenesis of granulomatous inflammation in the respiratory tract and autoimmunity in Wegener granulomatosis (WG) are poorly understood. Since mucociliar clearance represents the first major line of defence in the respiratory tract and its breakdown facilitates chronic inflammation, we investigated ciliary beat frequency (CBF) in WG. METHODS: Nasal epithelial cells were obtained from 30 patients with WG with involvement of the upper respiratory tract, 12 patients with other inflammatory rheumatic disease and 10 healthy controls. CBF was measured at 5 and 24 h after collection. RESULTS: were correlated with clinical data. Results: CBF was significantly reduced in WG compared to disease and healthy controls after 5 and 24 h. In WG, CBF almost stagnated after 24 h. Reduction of CBF correlated with the cumulative number of immunosuppressive agents in WG, but not in disease controls. No correlation was found between CBF impairment and cyclophosphamide levels, disease extent, disease activity, disease duration, serological and microbiological findings, or inflammation markers. CONCLUSION: CBF is severely impaired in WG, potentially influenced by immunosuppressive treatment. To what extent CBF impairment and subsequent barrier dysfunction are caused by other factors still has to be elucidated. Supportive measures to improve mucociliary clearance should be discussed in patients with WG.


Assuntos
Cílios/fisiologia , Granulomatose com Poliangiite/fisiopatologia , Mucosa Nasal/ultraestrutura , Análise de Variância , Autoimunidade/fisiologia , Estudos de Casos e Controles , Cílios/ultraestrutura , Feminino , Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/patologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Depuração Mucociliar , Mucosa Nasal/patologia , Fatores de Tempo
13.
Eur Spine J ; 18(8): 1226-33, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19387703

RESUMO

Sacral insufficiency fractures can cause severe, debilitating pain to patients concerned. The incidence of this fracture type correlates with the appearance of osteoporosis in the elderly population. A polymethylmethacrylate (PMMA) cement injection procedure called sacroplasty has been recently described as an optional method for the treatment of this fracture type. However, the correct cement placement in the complex anatomical structure of the sacrum is a surgical challenge. The aim of the study is to compare the precision, safety, and radiation exposure of standard multiplanar fluoroscopy and computed tomography (CT) guidance for PMMA application to the sacrum using both balloon-assisted sacroplasty and conventional sacroplasty. A controlled experimental investigation in a human cadaver trial has been performed. Two imaging and two application modalities to monitor percutaneous PMMA injection to the sacrum were examined. The application forms were randomized from side to side of the pelvis. We found less cement extravasation in the CT-guided groups, but also a significant higher radiation exposure (P < 0.05) by using CT guidance. The conventional fluoroscopy-guided sacroplasty revealed the shortest procedure time (incision to closure time) of all treatment groups (P < 0.01). These findings show no difference regarding cement extravasation between ballon-assisted and conventional sacroplasty. Further, in comparison to fluoroscopy-assisted technique, the CT-guided cement injection seems to decrease the risk of cement extravasation, irrespective of the use of an additional balloon assistance. However, we have to consider a greater radiation exposure using CT guidance. Further investigations will proof the suitability in the normal course of clinical life.


Assuntos
Fluoroscopia/métodos , Neuronavegação/métodos , Sacro/diagnóstico por imagem , Sacro/cirurgia , Tomografia Computadorizada por Raios X/métodos , Vertebroplastia/métodos , Idoso , Idoso de 80 Anos ou mais , Cimentos Ósseos/uso terapêutico , Cadáver , Fluoroscopia/efeitos adversos , Humanos , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/prevenção & controle , Osteoporose/complicações , Polimetil Metacrilato/uso terapêutico , Doses de Radiação , Lesões por Radiação/prevenção & controle , Fatores de Risco , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/cirurgia , Tomografia Computadorizada por Raios X/efeitos adversos , Vertebroplastia/instrumentação
14.
Med Klin Intensivmed Notfmed ; 114(8): 699-707, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28871441

RESUMO

INTRODUCTION: The aim of this clinical registry is to record the use of CytoSorb® adsorber device in critically ill patients under real-life conditions. METHODS: The registry records all relevant information in the course of product use, e. g., diagnosis, comorbidities, course of the condition, treatment, concomitant medication, clinical laboratory parameters, and outcome (ClinicalTrials.gov Identifier: NCT02312024). Primary endpoint is in-hospital mortality as compared to the mortality predicted by the APACHE II and SAPS II score, respectively. RESULTS: As of January 30, 2017, 130 centers from 22 countries were participating. Data available from the start of the registry on May 18, 2015 to November 24, 2016 (122 centers; 22 countries) were analyzed, of whom 20 centers from four countries provided data for a total of 198 patients (mean age 60.3 ± 15.1 years, 135 men [68.2%]). In all, 192 (97.0%) had 1 to 5 Cytosorb® adsorber applications. Sepsis was the most common indication for CytoSorb® treatment (135 patients). Mean APACHE II score in this group was 33.1 ± 8.4 [range 15-52] with a predicted risk of death of 78%, whereas the observed mortality was 65%. There were no significant decreases in the SOFA scores after treatment (17.2 ± 4.8 [3-24]). However interleukin-6 levels were markedly reduced after treatment (median 5000 pg/ml before and 289 pg/ml after treatment, respectively). CONCLUSIONS: This third interim report demonstrates the feasibility of the registry with excellent data quality and completeness from 20 study centers. The results must be interpreted with caution, since the numbers are still small; however the disease severity is remarkably high and suggests that adsorber treatment might be used as an ultimate treatment in life-threatening situations. There were no device-associated side effects.


Assuntos
Estado Terminal , Circulação Extracorpórea/métodos , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Escore Fisiológico Agudo Simplificado , APACHE , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros
15.
Int J Pharm ; 346(1-2): 109-18, 2008 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-17723283

RESUMO

Intestinal microparticle uptake is important for drug delivery, environmental pollution and multiple organ dysfunction syndrome. This paper explores further whether uptake occurs at mucosa associated lymphoid tissue (MALT) via the microfold (M) cells of Peyer's patch domes or through villous epithelium. It does this by comparing the results of exposure of either severe combined immunodeficient (SCID) mice (lacking MALT) or normal BALBc mice, to oral gavage with 2 microm fluorescent latex microparticles. At 5 and 30 min after gavage, full circumference samples along the small intestine were processed for fluorescence microscopy and microparticle numbers were collected for surface and tissue sites. Uptake occurred in both BALBc and SCID mice within 5 min of particle administration and increased further in the following 25 min. In BALBc mice, almost all particles (96%) are in non-MALT sites in MALT circumference samples, with very few at the domes: uptake was also substantial in entirely villous samples. In SCID mice, particle numbers were only slightly lower than those of the BALBc mice, and occurred exclusively by the villous route. These findings confirm that the villous uptake route must be considered when assessing the extent of the dose delivered following pharmaceutical or toxicological oral exposure to microparticles.


Assuntos
Absorção Intestinal , Mucosa Intestinal/metabolismo , Microesferas , Animais , Mucosa Intestinal/anatomia & histologia , Intestino Delgado/anatomia & histologia , Intestino Delgado/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Nódulos Linfáticos Agregados/anatomia & histologia , Nódulos Linfáticos Agregados/metabolismo , Imunodeficiência Combinada Severa
16.
PLoS One ; 13(2): e0191544, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29420567

RESUMO

OBJECTIVES: Shiga-toxin producing O157:H7 Entero Haemorrhagic E. coli [STEC/EHEC] are the most common cause of Haemolytic Uraemic Syndrome [HUS] related to infectious haemorrhagic colitis. Nearly all recommendations on long term treatment of EHEC infections refer to this strain. The 2011 outbreak in Northern Europe was the first of this dimension to be caused by the serotype O104:H4. We report on the 3.5 year follow up of 61 patients diagnosed with symptomatic EHEC O104:H4 infection in spring 2011. METHODS: Patients with EHEC O104 infection were followed in a monocentric, prospective observational study at four time points: 4, 12, 24 and 36 months. These data include the patients' histories, clinical findings, and complications. RESULTS: Sixty-one patients suffering from EHEC O104:H4 associated enterocolitis participated in the study at the time of hospital discharge. The mean age of patients was 43 ± 2 years, 37 females and 24 males. 48 patients participated in follow up 1 [FU 1], 34 patients in follow up 2 [FU 2], 23 patients in follow up 3 [FU 3] and 18 patients in follow up 4 [FU 4]. Out of 61 patients discharged from the hospital and included in the study, 54 [84%] were examined at least at one additional follow up. Serum creatinine decreased significantly between discharge and FU 1 from 1.3 ± 0.1 mg/dl to 0.7 ± 0.1 mg/dl [p = 0.0045]. From FU 1 until FU 4, no further change in creatinine levels could be observed. The patients need of antihypertensive medications decreased significantly [p = 0.0005] between discharge and FU 1 after four months. From FU 1 until FU 3, 24 months later, no further significant change in antihypertensive treatment was observed. CONCLUSIONS: Our findings suggest that patients free of pathological findings at time of discharge do not need a specific follow up. Patients with persistent health problems at hospital discharge should be clinically monitored over four months to evaluate chronic organ damage. Progressive or new emerging renal damage could not be observed over time in any patient.


Assuntos
Escherichia coli Êntero-Hemorrágica/patogenicidade , Infecções por Escherichia coli/terapia , Adulto , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
17.
Rev Sci Instrum ; 78(4): 043508, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17477661

RESUMO

We present the development and application of a diagnostic system for the analysis of microwave generated low-pressure plasmas, which might also be used for the investigation of the edge regions in magnetically confined fusion plasmas. Our method uses planar laser-induced fluorescence, which is produced by excitation of neutral metastable atoms through a short, intense, pulsed laser. The beam expansion optics consist of an uncommon setup of four lenses. By controlled shifting of an element of the optics sideways, the location of the laser sheet in the plasma is scanned perpendicular to the excitation plane. Together with a spectrometer observing different observation volumes along the beam path, we are able to map absolute three-dimensional (3D) population density distributions of the metastable ((2)P(12) (o)) 3s[12](0) (o) state of Ne I in an electron cyclotron resonance heating (ECRH) plasma. This optical tomography system was used to study the influence of the microwave power and mode on the spatial structure of the plasma. The results show that the population density of the neutral neon in this metastable state is found to be in the range of 10(16) m(-3), and that its spatial distribution is associated with the 3D structure of the magnetic field. We also report that the spatial distribution strongly varies with the mode structure, which depends on the microwave power.

18.
Rev Sci Instrum ; 78(12): 123110, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18163723

RESUMO

Carbon containing plasmas play an important role not only in plasma technology but also in thermonuclear fusion research. In order to understand and control the processes taking place in the plasma, the knowledge of the carbon ground state density is of major importance. It can be determined by absorption and emission spectroscopy. Detailed measurements were performed in the past to determine the silicon ground state density by means of spectroscopy of the self-absorbed spectral lines of the silicon ground state multiplet at 251 nm. The same procedure was applied for the determination of the carbon concentration, for which the carbon multiplet at 165 nm was analyzed and compared to a simulated spectrum. The ground state density was determined by two independent methods.

19.
Cancer Res ; 60(24): 6836-40, 2000 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-11156375

RESUMO

Although micrometastatic cancer cells in lymph nodes can be detected by monoclonal antibodies against epithelial or tumor-associated antigens, it remains unclear whether these cells are precursors of overt metastases or shedded tumor cells with a limited life span. Here we used esophageal cancer as a model to evaluate the prognostic significance and biological characteristics of such micrometastases. In lymph nodes classified as tumor free by conventional histopathological staging, tumor cells were identified with monoclonal antibody Ber-EP4 in 89 of 126 patients (71%) with completely resected (R0) esophageal carcinomas. Multivariate survival analysis underlined the strong and independent prognostic significance of Ber-EP4-positive cells in "node-negative" (pN0) patients. To assess the biology of Ber-EP4-positive cells, we established tumor cell lines from an immunohistochemically positive lymph node and the autologous primary tumor. p53 mutational analysis and multiplex-fluorescence in situ hybridization revealed common aberrations shared between both cell lines, whereas an insertion of chromosome 13 material in the short arm of chromosome 1 was only observed in micrometastatic cells. The tumorigenicity and metastatic potential of both cell lines were demonstrated in severe combined immunodeficient mice. In conclusion, our data provide first direct evidence for the malignant potential of micrometastatic cancer cells.


Assuntos
Neoplasias Esofágicas/genética , Linfonodos/metabolismo , Metástase Linfática , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Animais , Anticorpos Monoclonais , Aberrações Cromossômicas , Cromossomos Humanos Par 13 , Análise Mutacional de DNA , Feminino , Genes p53/genética , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Camundongos , Camundongos SCID , Repetições de Microssatélites , Análise Multivariada , Transplante de Neoplasias , Prognóstico , Análise de Sequência de DNA , Fatores de Tempo , Células Tumorais Cultivadas
20.
Biochim Biophys Acta ; 1091(3): 261-9, 1991 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-2001409

RESUMO

Of eleven agglutinating lectins tested, only one, Ulex europaeus agglutinin I (UEA1), stimulated Ca2+ uptake in quin2-loaded erythrocytes by about 2-fold. UEA1 is known to be an alpha-L-fucose and ABH blood group specific lectin. The 45Ca2+ influx induced by UEA1 was absent in the presence of extracellular fucose (5 and 15 mM) and depended on the ABH blood group of the donor, the stimulatory potency of the lectin decreasing in the order H greater than A2 greater than A1. Ca2+ entry blockers, such as cobalt and verapamil, did not affect the 45Ca2+ influx induced by UEA1. 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) inhibited dose-dependently with a Ki of 1-2 microM. 10 microM DIDS, 10 microM 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS) and 20 microM dipyridamole fully blocked the 45Ca2+ influx induced by UEA1. The effect of UEA1 on 45Ca2+ influx was absent in K+ and Mg2+ media and was less pronounced in choline than in Na+ media. The 45Ca2+ influx induced by the lectin was abolished by preincubation with 12-O-tetradecanoylphorbol 13-acetate (TPA, 60 ng/ml). A monoclonal antibody raised against A1 erythrocytes (Bric 54) accelerated 45Ca2+ influx in quin2 loaded A1 erythrocytes by about 2-fold. No effect was seen in A2 and H erythrocytes. The 45Ca2+ influx elicited by Bric 54 exhibited a sensitivity towards inhibition by DIDS and TPA, as well as a dependence on the cation composition of the incubation medium similar to that observed with UEA1. The effects of UEA1 and Bric 54 were not additive. These observations suggest that the Ca2+ influx induced by UEA1 and Bric 54 is mediated by the same transport pathway. Since both the lectin and the antibody exhibit ABH blood group specificity, it appears reasonable to conclude that ABH antigens can serve as recognition sites for activation of a Ca2+ influx pathway in human erythrocytes, which is sensitive to inhibitors of the band 3 anion-exchanger.


Assuntos
Ácido 4-Acetamido-4'-isotiocianatostilbeno-2,2'-dissulfônico/análogos & derivados , Sistema ABO de Grupos Sanguíneos/fisiologia , Anticorpos Monoclonais/farmacologia , Cálcio/sangue , Eritrócitos/metabolismo , Lectinas/farmacologia , Lectinas de Plantas , Ácido 4,4'-Di-Isotiocianoestilbeno-2,2'-Dissulfônico , Ácido 4-Acetamido-4'-isotiocianatostilbeno-2,2'-dissulfônico/farmacologia , Aminoquinolinas , Transporte Biológico Ativo/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Eritrócitos/imunologia , Corantes Fluorescentes , Humanos , Cinética , Potássio/sangue , Rubídio/sangue , Sódio/sangue
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