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1.
Anaesthesist ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32960284

RESUMO

BACKGROUND: Delays in the start of morning operations cause a loss of expensive OR capacity as well as frustration and potential conflicts among the different professions involved. There are a lot of reasons which can lead to delayed anesthesia ready time (ART). This is the first large multicenter study to identify incidence, extent and reasons of delay in ART. METHODS: First case delays in ART were studied in all regular ORs in 36 hospitals of different sizes (smaller community hospitals, larger community hospitals and university hospitals) over a period of 2 weeks. We analyzed the results comparing the 3 hospital types regarding incidence, extent and reasons for delay. RESULTS: A total of 3628 first of day cases were included in the study. Incidences of delayed ART (delay >5 min) ranged from 26.5% in university hospitals to 40.8% in larger community hospitals. However, university hospitals had higher incidences than smaller community hospitals of delays greater than 15 and 30 min. The main reasons for delays were prolonged induction of anesthesia, patient in-hospital logistics and delayed patient arrival at the hospitals. The highest mean delay of delayed cases was found in university hospitals with 21.7 min ± 14.7 min (SD). CONCLUSIONS: Delays in anesthesia ready time have a high prevalence in most hospitals, however the reasons for delay are manifold, making interventions to reduce delay complex.

2.
Chirurg ; 2020 Jun 22.
Artigo em Alemão | MEDLINE | ID: mdl-32572499

RESUMO

BACKGROUND: Delays in beginning operations in the morning lead to a loss of valuable operating time and can cause frustration among the medical personnel involved. OBJECTIVE: So far there are no prospective, multicentric investigations of the incidence and reasons for delayed first incision times in the morning. The effect of planning list instability of first cases on late operating room starts has not yet been evaluated. MATERIAL AND METHODS: In this multicenter prospective study delays in surgical incision time in all first cases of the day were investigated in 36 German and Swiss hospitals (14 surgical specialties) over a period of 2 weeks. RESULTS: A total of 3628 first of the day cases were included in the study. Looking at all subspecialties combined 50.8% of the first cases of the day were delayed by more than 5 min and in 30.2% of cases longer than 15 min. Incidences of delayed surgical incision time >5 min ranged from 40.0% (gynecology) to 66.8% (neurosurgery). The main reasons for delays in ascending order were prolonged induction of anesthesia compared to the planned time, the delayed appearance of the surgeon and prolonged preparation for surgery. The incidence of delays in incision times for planning list instability was increased by 10% and the average delay increased by 7 min. CONCLUSION: Delays in surgical incision times of the first operation of the day have a high incidence in most surgical specialties; however, the reasons for delays are manifold. Plan instability of operating room lists with respect to the first cases has a negative effect on the punctuality of the incision time and should therefore be avoided.

3.
4.
Mol Cell Endocrinol ; 499: 110586, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31539598

RESUMO

Placental syncytiotrophoblast (ST) is considered as the main placental endocrine tissue secreting progesterone, a steroid essential for maintenance of pregnancy. However, each step of progestins production has been poorly investigated in villous cytotrophoblast (VCT) regarding ST formation. We aimed to characterize progestins production during human differentiation of VCT into ST. VCTs were isolated from term placenta and cultivated, with or without forskolin (FSK), to stimulate trophoblast differentiation. Secreted progestins concentrations were determined by immuno-assay and Gas Chromatography-tandem mass spectrometry. Intracellular expression of cholesterol transporter and enzymes involved in steroidogenesis were studied by immunofluorescence, western-blot, and RT-qPCR. Progesterone and pregnenolone are produced by VCT and their secretion increases with VCT differentiation while 17-hydroxyprogesterone concentration remains undetectable. HSD3B1 enzyme expression increases whereas MLN64, the cholesterol placental mitochondrial transporter and P450SCC expressions do not. FSK induces progestins production. Progestins placental synthesis is effective since VCT and increases with ST formation thanks to mitochondria.


Assuntos
Complexos Multienzimáticos/metabolismo , Placenta/metabolismo , Progesterona Redutase/metabolismo , Progestinas/metabolismo , Esteroide Isomerases/metabolismo , Fator 4 Associado a Receptor de TNF/metabolismo , Trofoblastos/citologia , 17-alfa-Hidroxiprogesterona/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Colforsina/farmacologia , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Regulação da Expressão Gênica , Humanos , Complexos Multienzimáticos/genética , Gravidez , Pregnenolona/metabolismo , Progesterona/metabolismo , Progesterona Redutase/genética , Esteroide Isomerases/genética , Fator 4 Associado a Receptor de TNF/genética , Trofoblastos/metabolismo
5.
Anaesthesist ; 68(4): 218-227, 2019 04.
Artigo em Alemão | MEDLINE | ID: mdl-30895350

RESUMO

BACKGROUND: Minimum volume thresholds for specific surgical procedures in German hospitals were established in 2004 but remain controversial. For the first time, this study investigated the relationship between hospital performance volume and surgical procedure duration in a multicenter approach. The question here was whether a concentration on frequently performed procedures leads to a reduction in surgical process times. METHODS: In a retrospective analysis, the 5 most common procedures from visceral, trauma/orthopedic and gynecological/obstetrics surgery were examined in hospitals participating in a benchmarking program. For each procedure performed between 2013 and 2015, hospitals were divided into 4 groups depending on the hospital volume provided. The average surgical duration of incision to suture time was calculated between the group with "very low" hospital volume and the other three groups ("low", "high" and "very high"). RESULTS: OR cases from 75 hospitals were analyzed. The number of included cases per procedure ranged from 31,940 to 2705. The average number of operations performed in a specific procedure was 3-4 times higher in high-volume hospitals compared to very low-volume hospitals. A linear relationship between hospital volume and surgical process time only appeared to be clearly seen in laparoscopic cholecystectomy, appendectomy and arthroscopic meniscus surgery: a higher case load led to a reduction in incision to suture time. For the other procedures, the surgical process times were inconsistent between the hospital groups. CONCLUSION: The case volume only appeared to have a direct but limited influence on incision to suture times in laparoscopic and arthroscopic procedures. Overall, the hospital performance volume appeared to be of subordinate importance in terms of OR-economics.


Assuntos
Hospitais com Alto Volume de Atendimentos , Hospitais com Baixo Volume de Atendimentos , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Benchmarking , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Ginecologia , Pesquisa sobre Serviços de Saúde , Preços Hospitalares , Humanos , Obstetrícia , Duração da Cirurgia , Procedimentos Ortopédicos , Ortopedia , Gravidez , Estudos Retrospectivos
7.
J Psychosom Res ; 111: 133-139, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29935747

RESUMO

OBJECTIVE: The main objective of this study was a detailed comparison of the level of anxiety about surgery and anesthesia. Other objectives included the assessment of the prevalence and intensity of preoperative anxiety. METHODS: This cross-sectional single-center survey used the validated Amsterdam anxiety and information scale (APAIS) and a modified numeric rating scale (mNRS) to assess preoperative anxiety, anxiety about surgery and anxiety about anesthesia. Prevalences and intensities of anxieties were predominantly analyzed descriptively. RESULTS: 3200 patients were enrolled and 3087 (57% females) were analyzed. 92.6% reported preoperative anxiety according to APAIS scores. The average total APAIS anxiety score (APAIS-A-T) was 9.9 (SD 3.6). 40.5% reported high anxiety (defined as APAIS-A-T > 10). Mean anxiety about surgery (APAIS-A-Su) was higher than mean anxiety about anesthesia (APAIS-A-An): 5.5 (SD 2.1) vs. 4.3 (SD 1.9), p < 0.0001. Accordingly, more patients were substantially more afraid (score difference > 2) of surgery (642, 20.8%, 95% CI 19.4-22.3) than of anesthesia (48, 1.6%, 95% CI 1.2-2.1). CONCLUSION: Preoperative anxiety is still very common among adult patients scheduled to undergo an elective procedure. Therefore, it should be evaluated routinely. Anxiety about surgery and anxiety about anesthesia differ in many patients. For this reason, anxiety about surgery and anxiety about anesthesia should be assessed separately. This would allow providing a more individualized support of patients to cope with their anxiety and could require particular attention by the surgeon or the anesthetist.


Assuntos
Ansiedade/epidemiologia , Ansiedade/psicologia , Cuidados Pré-Operatórios/psicologia , Inquéritos e Questionários , Adaptação Psicológica/fisiologia , Adulto , Idoso , Ansiedade/diagnóstico , Estudos Transversais , Medo/fisiologia , Medo/psicologia , Feminino , Objetivos , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Prevalência
8.
Transpl Infect Dis ; 20(2): e12855, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29427356

RESUMO

BACKGROUND: Clostridium difficile infection (CDI) is a common complication of lung and allogeneic hematopoietic cell (HCT) transplant, but the epidemiology and outcomes of CDI after transplant are poorly described. METHODS: We performed a prospective, multicenter study of CDI within 365 days post-allogeneic HCT or lung transplantation. Data were collected via patient interviews and medical chart review. Participants were followed weekly in the 12 weeks post-transplant and while hospitalized and contacted monthly up to 18 months post-transplantation. RESULTS: Six sites participated in the study with 614 total participants; 4 enrolled allogeneic HCT (385 participants) and 5 enrolled lung transplant recipients (229 participants). One hundred and fifty CDI cases occurred within 1 year of transplantation; the incidence among lung transplant recipients was 13.1% and among allogeneic HCTs was 31.2%. Median time to CDI was significantly shorter among allogeneic HCT than lung transplant recipients (27 days vs 90 days; P = .037). CDI was associated with significantly higher mortality from 31 to 180 days post-index date among the allogeneic HCT recipients (Hazard ratio [HR] = 1.80; P = .007). There was a trend towards increased mortality among lung transplant recipients from 120 to 180 days post-index date (HR = 4.7, P = .09). CONCLUSIONS: The epidemiology and outcomes of CDI vary by transplant population; surveillance for CDI should continue beyond the immediate post-transplant period.


Assuntos
Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Pulmão/efeitos adversos , Transplantados , Feminino , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco
9.
Fungal Genet Biol ; 105: 16-27, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28579390

RESUMO

Development of novel strategies to control fungal plant pathogens requires understanding of their cellular organisation and biology. Live cell imaging of fluorescent organelle markers has provided valuable insight into various aspects of their cell biology, including invasion strategies in plant pathogenic fungi. Here, we introduce a set of 17 vectors that encode fluorescent markers to visualize the plasma membrane, endoplasmic reticulum (ER), chromosomes, the actin cytoskeleton, peroxisomes and autophagosomes in the wheat pathogen Zymoseptoria tritici. We fused either enhanced green-fluorescent protein (eGFP) or a codon-optimised version of GFP (ZtGFP) to homologues of a plasma membrane-located Sso1-like syntaxin, an ER signalling and retention peptide, a histone H1 homologue, the LifeAct actin-binding peptide, a mitochondrial acetyl-CoA dehydrogenase, a peroxisomal import signal and a homologue of the ubiquitin-like autophagosomal protein Atg8. We expressed these markers in wildtype strain IPO323 and confirmed the specificity of these markers by counterstaining or physiological experiments. This new set of molecular tools will help understanding the cell biology of the wheat pathogen Z. tritici.


Assuntos
Ascomicetos/metabolismo , Biomarcadores/metabolismo , Corantes Fluorescentes/metabolismo , Organelas/metabolismo , Actinas/metabolismo , Ascomicetos/genética , Ascomicetos/ultraestrutura , Retículo Endoplasmático/metabolismo , Proteínas Fúngicas/genética , Genes Fúngicos , Vetores Genéticos , Proteínas de Fluorescência Verde/metabolismo , Peroxissomos/metabolismo , Triticum/microbiologia
10.
Sci Rep ; 7(1): 3572, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28620237

RESUMO

Genetically engineered pigs are a promising source for islet cell transplantation in type 1 diabetes, but the strong human anti-pig immune response prevents its successful clinical application. Here we studied the efficacy of neonatal porcine islet-like cell clusters (NPICCs) overexpressing LEA29Y, a high-affinity variant of the T cell co-stimulation inhibitor CTLA-4Ig, to engraft and restore normoglycemia after transplantation into streptozotocin-diabetic NOD-SCID IL2rγ-/- (NSG) mice stably reconstituted with a human immune system. Transplantation of INSLEA29Y expressing NPICCs resulted in development of normal glucose tolerance (70.4%) and long-term maintenance of normoglycemia without administration of immunosuppressive drugs. All animals transplanted with wild-type NPICCs remained diabetic. Immunohistological examinations revealed a strong peri- and intragraft infiltration of wild-type NPICCs with human CD45+ immune cells consisting of predominantly CD4+ and CD8+ lymphocytes and some CD68+ macrophages and FoxP3+ regulatory T cells. Significantly less infiltrating lymphocytes and only few macrophages were observed in animals transplanted with INSLEA29Y transgenic NPICCs. This is the first study providing evidence that beta cell-specific LEA29Y expression is effective for NPICC engraftment in the presence of a humanized immune system and it has a long-lasting protective effect on inhibition of human anti-pig xenoimmunity. Our findings may have important implications for the development of a low-toxic protocol for porcine islet transplantation in patients with type 1 diabetes.


Assuntos
Abatacepte/genética , Expressão Gênica , Imunossupressão , Ilhotas Pancreáticas/metabolismo , Animais , Biomarcadores , Sobrevivência Celular , Técnicas de Inativação de Genes , Xenoenxertos , Humanos , Imunidade/genética , Imuno-Histoquímica , Imunofenotipagem , Imunossupressão/métodos , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Suínos
11.
Mol Cell Endocrinol ; 450: 105-112, 2017 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-28461075

RESUMO

Ovarian monitoring requires the determination of serum estradiol and progesterone levels. We investigated whole follicular steroidogenesis under rFSH in medically assisted procreation (MAP: 26 IVF, 24 ICSI) compared to 11 controls (IUI). Estrone, estradiol, Δ4-androstenedione, testosterone, progesterone and 17-hydroxyprogesterone were measured by immunoassay and mass spectrometry except for estrogens. At the start of a spontaneous or induced cycle, steroids levels fluctuated within normal ranges: estradiol (314-585 pmol/L), estrone (165-379 pmol/L) testosterone (1.3-1.6 nmol/L), Δ4-androstenedione (4.5-5.6 nmol/L), 17-hydroxyprogesterone (2.1-2.2 nmol/L) and progesterone (1.8-1.9 nmol/L). 17-hydroxyprogesterone, Δ 4-androstenedione and estradiol predominated. Then estradiol and oestrone levels rise, but less markedly for oestrone in IUI. In MAP, rFSH injections induce a sharp increase in estrogens associated with a rise in 17-hydroxyprogesterone and Δ4-androstenedione levels, disrupting oestrogen/androgen ratios. rFSH stimulation induces an ovarian hyperplasia and Δ4pathway which could become abnormal. Determining 17-hydroxyprogesterone and Δ4-androstenedione levels with LC-MS/MS may therefore be useful in managing recurrent MAP failures.


Assuntos
17-alfa-Hidroxiprogesterona/sangue , Androstenodiona/sangue , Hormônio Foliculoestimulante/farmacologia , Espectrometria de Massas , Folículo Ovariano/patologia , Proteínas Recombinantes/farmacologia , Reprodução/efeitos dos fármacos , Feminino , Humanos , Hiperplasia , Folículo Ovariano/efeitos dos fármacos , Estudos Retrospectivos
12.
Anaesthesist ; 66(4): 233-239, 2017 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-28378133

RESUMO

Involvement of palliative care is so far not common practice for critically ill patients on surgical intensive care units (ICUs) in Germany. The objectives of palliative care concepts are improvement of patient quality of life by relief of disease-related symptoms using an interdisciplinary approach and support of patients and their relatives considering their current physical, psychological, social and spiritual needs. The need for palliative care can be identified via defined screening criteria. Integration of palliative care can either be realized using a consultative model which focusses on involvement of palliative care consultants or an integrative model which embeds palliative care principles into the routine daily practice by the ICU team. Early integration of palliative care in terms of advance care planning (ACP) can lead to an increase in goals of care discussions and quality of life as well as a decrease of mortality and length of stay on the ICU. Moreover, stress reactions of relatives and ICU staff can be reduced and higher satisfaction with therapy can be achieved. The core of goal of care discussions is professional and well-structured communication between patients, relatives and staff. Consideration of palliative care principles by model-based integration into ICU practice can improve complex intensive care courses of disease in a productive but dignified way without neglecting curative attempts.


Assuntos
Cuidados Críticos/tendências , Cuidados Paliativos/tendências , Planejamento Antecipado de Cuidados , Humanos , Assistência Terminal
13.
Rhinology ; 55(1): 81-89, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28060384

RESUMO

BACKGROUND: Nasal and paranasal cavities are supposed to contribute substantially to the vocal tract resonator properties. However, their acoustical effects as well as the effects of sinus surgery on the voice remain unclear. In this work we investigate resonance phenomena of paranasal sinuses prior to and after various rhinosurgical procedures in cadaveric human sinonasal tracts and corresponding 3D casts. METHODOLOGY: Nasal and paranasal cavities of formalin-preserved cadavers and corresponding 3D replicas were excited by sine-tone sweeps from an earphone placed in the epipharynx. The response was picked up by a microphone at the nostrils. Different FESS procedures were performed and the acoustical responses following excitation were recorded. The measured acoustical changes in the obtained transfer functions were then evaluated. RESULTS: Marked low frequency dips were detected in the transfer functions when sinus cavities were included in the nasal resonator system. These dips showed a significant correlation with sinus volumes. Following FESS procedures they moved upwards in frequency depending on the extent of the surgical intervention. CONCLUSIONS: The transfer functions obtained in cadaveric situs and 3D replicas showed dips at the resonance frequencies of the paranasal cavities. Marked acoustic effects in terms of increase in dip frequency following FESS procedures were reproducibly documented.


Assuntos
Endoscopia , Seios Paranasais/cirurgia , Acústica da Fala , Qualidade da Voz/fisiologia , Cadáver , Humanos , Cavidade Nasal/diagnóstico por imagem , Cavidade Nasal/cirurgia , Seios Paranasais/diagnóstico por imagem , Tomografia Computadorizada por Raios X
15.
Leukemia ; 31(7): 1491-1501, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-27899802

RESUMO

Children with P2RY8-CRLF2-positive acute lymphoblastic leukemia have an increased relapse risk. Their mutational and transcriptional landscape, as well as the respective patterns at relapse remain largely elusive. We, therefore, performed an integrated analysis of whole-exome and RNA sequencing in 41 major clone fusion-positive cases including 19 matched diagnosis/relapse pairs. We detected a variety of frequently subclonal and highly instable JAK/STAT but also RTK/Ras pathway-activating mutations in 76% of cases at diagnosis and virtually all relapses. Unlike P2RY8-CRLF2 that was lost in 32% of relapses, all other genomic alterations affecting lymphoid development (58%) and cell cycle (39%) remained stable. Only IKZF1 alterations predominated in relapsing cases (P=0.001) and increased from initially 36 to 58% in matched cases. IKZF1's critical role is further corroborated by its specific transcriptional signature comprising stem cell features with signs of impaired lymphoid differentiation, enhanced focal adhesion, activated hypoxia pathway, deregulated cell cycle and increased drug resistance. Our findings support the notion that P2RY8-CRLF2 is dispensable for relapse development and instead highlight the prominent rank of IKZF1 for relapse development by mediating self-renewal and homing to the bone marrow niche. Consequently, reverting aberrant IKAROS signaling or its disparate programs emerges as an attractive potential treatment option in these leukemias.


Assuntos
Fusão Gênica , Genômica , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Receptores de Citocinas/genética , Receptores Purinérgicos P2Y/genética , Transcrição Genética , Adolescente , Criança , Pré-Escolar , Dosagem de Genes , Genes Supressores de Tumor , Humanos , Fator de Transcrição Ikaros/genética , Fator de Transcrição Ikaros/fisiologia , Lactente , Janus Quinases/fisiologia , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição STAT/fisiologia
16.
Laryngorhinootologie ; 95(9): 610-9, 2016 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-26990935

RESUMO

BACKGROUND: In recent years interactions between surgical treatment of oral carcinoma and incidence of anxiety or depression have become a subject of discussions. This prospective study is a comparison between the extent of loss of speech intelligibility and presence of depressive symptoms or anxiety as a result of oral carcinoma. MATERIAL AND METHODS: One year after surgical therapy for oral carcinoma, 90 patients of an average age of 60±12 years were examined. Their speech intelligibility degree was measured using standardized automatic speech recognition (word recognition rate, WR). Symptoms of anxiety and depression were detected by use of HAD-Scales (HADS). Next to the relationship between WR and HADS other influential variables related to WR and HADS were statistically evaluated. RESULTS: The WR average was 53.2±17.2. Female WR was better than male. The difference between tumor classifications T1 and T4 compared to the WR reached statistical significance. Significant differences were detected between WR and "tumor localization", "graft donor site", "graft morphology", "tongue motility", and "tracheostoma" groups. There was a relationship between tongue motility and graft morphology, graft donor site and tumor localization. HAD-Scores in the mean were elevated: HADS-Total=43.3%, HADS-A=43.3% und HADS-D= 51.1%. WR correlates with HADS-D-Subscale, but not with HADS-A-Subscale. CONCLUSION: Communication disorders as a result of neoplasmic orofacial surgery may be related to extent of the treatment and to affective impairments. This should receive attention in the concept of rehabilitation.


Assuntos
Transtornos de Ansiedade , Neoplasias Bucais/cirurgia , Inteligibilidade da Fala , Idoso , Ansiedade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
17.
Leukemia ; 30(4): 767-75, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26601784

RESUMO

The process of blood formation, haematopoiesis, depends upon a small number of haematopoietic stem cells (HSCs) that reside in the bone marrow. Differentiation of HSCs is characterised by decreased expression of genes associated with self-renewal accompanied by a stepwise activation of genes promoting differentiation. Lineage branching is further directed by groups of cooperating and counteracting genes forming complex networks of lineage-specific transcription factors. Imbalances in such networks can result in blockage of differentiation, lineage reprogramming and malignant transformation. CCAAT/enhancer-binding protein-α (C/EBPα) was originally identified 30 years ago as a transcription factor that binds both promoter and enhancer regions. Most of the early work focused on the role of C/EBPα in regulating transcriptional processes as well as on its functions in key differentiation processes during liver, adipogenic and haematopoietic development. Specifically, C/EBPα was shown to control differentiation by its ability to coordinate transcriptional output with cell cycle progression. Later, its role as an important tumour suppressor, mainly in acute myeloid leukaemia (AML), was recognised and has been the focus of intense studies by a number of investigators. More recent work has revisited the role of C/EBPα in normal haematopoiesis, especially its function in HSCs, and also started to provide more mechanistic insights into its role in normal and malignant haematopoiesis. In particular, the differential actions of C/EBPα isoforms, as well as its importance in chromatin remodelling and cellular reprogramming, are beginning to be elucidated. Finally, recent work has also shed light on the dichotomous function of C/EBPα in AML by demonstrating its ability to act as both a tumour suppressor and promoter. In the present review, we will summarise the current knowledge on the functions of C/EBPα during normal and malignant haematopoiesis with special emphasis on the recent work.


Assuntos
Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Neoplasias Hematológicas/fisiopatologia , Hematopoese/fisiologia , Animais , Humanos
18.
HNO ; 64(1): 41-8, 2016 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-26666558

RESUMO

BACKGROUND: Optical diagnostic methods may simplify and improve the early diagnosis of tumours of the upper aerodigestive tract; however, these have not yet found their way into clinical routine. OBJECTIVE: This article aims to define the problems that have prevented routine use of optical diagnostic methods so far, as well as listing and also explaining potential trendsetting approaches to overcome these difficulties. MATERIALS AND METHODS: The study is based on a combined analysis of publically accessible databases (PubMed MEDLINE, Thompson Reuters Web of Science, SPIE. Digital Library; full time period available; search strings: "oral cavity", "pharynx", "larnyx", "optical diagnosis", "optical biopsy", "optical coherence tomography", "confocal endomicroscopy", "fluorescence endoscopy", "narrow band imaging", "non-linear imaging", "fluorescence lifetime imaging"), as well as personal experiences. RESULTS: Both conceptual and methodical problems were determined, and possible solutions based on current developments are discussed. CONCLUSION: Optical diagnostic methods have the potential to revolutionise early diagnosis of upper aerodigestive tract malignancies, providing the different hurdles listed in this review can be overcome.


Assuntos
Detecção Precoce de Câncer/tendências , Previsões , Neoplasias Gastrointestinais/patologia , Lesões Pré-Cancerosas/patologia , Neoplasias do Sistema Respiratório/patologia , Tomografia Óptica/tendências , Medicina Baseada em Evidências , Humanos
19.
Schmerz ; 30(2): 166-73, 2016 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-26242358

RESUMO

BACKGROUND: Preoperative anxiety is not systematically assessed during premedication appointments, although it may influence the postoperative course and outcome. OBJECTIVES: The aim of this study was to assess preoperative anxiety in a sample of patients before major urological surgery and to characterize the impact on postoperative pain. An additional aim was to analyze the agreement between patients' self-ratings and physicians' anxiety ratings. PATIENTS AND METHODS: In all, 127 male and 27 female patients participated in a prospective observational study. Preoperative anxiety was assessed with two validated instruments - the APAIS (Amsterdam Preoperative Anxiety and Information Scale) and the State Scale of the STOA questionnaire (State-Trait Operation Anxiety) - during the premedication appointment. Physicians provided their subjective ratings on patients' anxiety and need for information using the APAIS. The predictive value of preoperative anxiety for postoperative pain was evaluated. RESULTS: Nearly four out of ten patients were identified as "anxiety cases"; thereof women were more afraid than men were. Preoperative anxiety was not correctly assessed by physicians, who overestimated patients' anxiety. In female patients, preoperative anxiety was predictive of increased postoperative pain scores. CONCLUSION: Preoperative anxiety is a frequent concern and often not correctly assessed by physicians. The use of scoring systems to detect preoperative anxiety is useful in clinical routine and helps to decide on therapeutic interventions.


Assuntos
Ansiedade/complicações , Ansiedade/psicologia , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/psicologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/psicologia , Período Pré-Operatório , Procedimentos Cirúrgicos Urológicos/psicologia , Ansiedade/diagnóstico , Feminino , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco , Estatística como Assunto , Inquéritos e Questionários , Resultado do Tratamento
20.
Leukemia ; 30(3): 701-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26526988

RESUMO

Peripheral T-cell lymphomas (PTCLs) are aggressive lymphomas with no effective upfront standard treatment and ineffective options in relapsed disease, resulting in poorer clinical outcomes as compared with B-cell lymphomas. The adoptive transfer of T cells engineered to express chimeric antigen receptors (CARs) is a promising new approach for treatment of hematological malignancies. However, preclinical reports of targeting T-cell lymphoma with CARs are almost non-existent. Here we have designed a CAR, CD4CAR, which redirects the antigen specificity of CD8+ cytotoxic T cells to CD4-expressing cells. CD4CAR T cells derived from human peripheral blood mononuclear cells and cord blood effectively redirected T-cell specificity against CD4+ cells in vitro. CD4CAR T cells efficiently eliminated a CD4+ leukemic cell line and primary CD4+ PTCL patient samples in co-culture assays. Notably, CD4CAR T cells maintained a central memory stem cell-like phenotype (CD8+CD45RO+CD62L+) under standard culture conditions. Furthermore, in aggressive orthotropic T-cell lymphoma models, CD4CAR T cells efficiently suppressed the growth of lymphoma cells while also significantly prolonging mouse survival. Combined, these studies demonstrate that CD4CAR-expressing CD8+ T cells are efficacious in ablating malignant CD4+ populations, with potential use as a bridge to transplant or stand-alone therapy for the treatment of PTCLs.


Assuntos
Transferência Adotiva , Linfócitos T CD8-Positivos/imunologia , Linfoma de Células T Periférico/terapia , Proteínas Mutantes Quiméricas/genética , Receptores Artificiais/genética , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/transplante , Engenharia Celular , Linhagem Celular Tumoral , Técnicas de Cocultura , Citotoxicidade Imunológica , Expressão Gênica , Humanos , Leucemia/genética , Leucemia/imunologia , Leucemia/patologia , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/imunologia , Linfoma de Células T Periférico/mortalidade , Masculino , Camundongos , Camundongos Endogâmicos NOD , Proteínas Mutantes Quiméricas/imunologia , Transplante de Neoplasias , Cultura Primária de Células , Receptores Artificiais/imunologia , Análise de Sobrevida
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