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1.
Tijdschr Psychiatr ; 62(1): 47-53, 2020.
Artigo em Holandês | MEDLINE | ID: mdl-31994711

RESUMO

BACKGROUND: Researchers that try to identify the relationship between hope and mental health often lack a conceptual understanding of 'hope'. Nonetheless, experiences of despair that are central in depression seem to surpass our everyday understanding of hope and hopelessness. How can this despair be understood and recognized? OBJECTIVE To describe depression through a phenomenological understanding of hope and to explore how this insight relates to our current definition of depression as a mood disorder, as well as to clinical practice.
RESULTS: Existential hope arises spontaneously in our experience of the world and through the relationship with significant others. A significant part of the experience of depression amounts to the loss of existential hope. Depressive despair features a radically shifted experiential structure, which seems to be absent in demoralisation; this advocates the view of depression as a 'disorder of attunement'. A therapeutic relationship can recover the loss by cultivating a new sense of possibilities.
CONCLUSION: The idea of existential hope provides a new conceptual framework to understand the experience of depression as well as the possibility for its recovery.


Assuntos
Depressão , Autoimagem , Depressão/terapia , Humanos
2.
Tijdschr Psychiatr ; 59(8): 482-488, 2017.
Artigo em Holandês | MEDLINE | ID: mdl-28880349

RESUMO

BACKGROUND: The phenomenon of parental alienation can arise when a child allies with one parent and refuses to have contact with the other parent. The concept has attracted a great deal of attention over the last few years. There has been controversy about whether parental alienation should be recognised as a psychiatric syndrome of the alienated child caught up in a conflict between supporters and opponents.
AIM: To try to determine whether parental alienation belongs to psychiatric diagnostics.
METHOD: We made a careful study of various databases in order to find literature relating to parental alienation.
RESULTS: Parental alienation is situated on the border between psychiatry, sociology and justice. One of the main tasks of psychiatry in this border area is to safeguard the domain of diagnostics.
CONCLUSION: Because so much attention is being given to the question of whether parental alienation syndrome should be recognised as a diagnosis, there is often a tendency to ignore the possible impact of parental alienation and to pay very little attention to ways of coping with the problem.


Assuntos
Transtornos Mentais/psicologia , Relações Pais-Filho , Pais/psicologia , Rejeição em Psicologia , Alienação Social , Adaptação Psicológica , Adulto , Criança , Humanos
3.
Pathologe ; 37(Suppl 2): 217-222, 2016 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-27638528

RESUMO

Breast cancer can be divided into four molecular subtypes with different prognoses using immunohistochemical markers in the routine clinicopathological work-up. The protein Ki-67 is of central importance in this context, in particular to distinguish between luminal A and luminal B carcinomas. Determination of the Ki-67 index of a carcinoma also allows a prediction of the likelihood of the response to chemotherapy. Additionally, the expression of certain cytokeratins in tumor cells is associated with a poor response to chemotherapy. The heterogeneity of molecular subtypes with regard to the histological appearance indicates an even greater diversity of breast cancer. We were able to show that a high proportion of luminal B carcinomas display neuroendocrine differentiation. Further studies with particular emphasis on histomorphological criteria should be performed to attain a more accurate classification of breast cancer and to pave the way towards targeted therapies for a better prognosis in the future.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Mama/patologia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Neoplasias da Mama/classificação , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/genética , Tumores Neuroendócrinos/classificação , Prognóstico
4.
Ultraschall Med ; 36(6): 581-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26529354

RESUMO

PURPOSE: Ultrasound is a well-established noninvasive test for assessing patients with liver disease. This study aims to prospectively compare ultrasound to the new technique elastography (ARFI) for the assessment of liver fibrosis/cirrhosis. MATERIALS AND METHODS: High-frequency B-mode ultrasound (liver surface/vein irregularity, liver homogeneity, spleen size), ARFI quantification, mini-laparoscopic liver evaluation including biopsy were prospectively obtained in compensated patients scheduled for liver biopsy. For the diagnosis of cirrhosis, a combined gold standard (cirrhosis at histology and/or at macroscopic liver evaluation) was used. RESULTS: Out of 157 patients, 35 patients were diagnosed cirrhotic. Ultrasound (combination of liver vein and/or surface irregularity) showed no significant difference compared to ARFI quantification for the diagnosis of significant liver fibrosis (Ishak> = 3) and cirrhosis. Diagnosis of cirrhosis had a sensitivity/specificity/PPV/NPV of 83 %(±â€Š12) / 82 %(±â€Š7) / 57 %(±â€Š14) / 94 %(±â€Š4), respectively, with ultrasound and 86 %(±â€Š12) / 81 %(±â€Š7) / 57 %(±â€Š13) / 95 %(±â€Š4), respectively, with ARFI quantification. The sensitivity/specificity/PPV/NPV for the detection of significant fibrosis were 68 %(±â€Š13) / 86 %(±â€Š7) / 71 %(±â€Š13) / 84 %(±â€Š7), respectively, for ultrasound and 70 %(±â€Š12) / 84 %(±â€Š7) / 69 %(±â€Š12) / 84 %(±â€Š7), respectively, for ARFI quantification. CONCLUSION: ARFI elastography and high-frequency B-mode ultrasound show similar and good results for the diagnosis of compensated liver cirrhosis and high-grade fibrosis. A key benefit of both methods is the high NPV suggesting them as noninvasive exclusion tests.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Laparoscopia/métodos , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Idoso , Biópsia/métodos , Medicina Baseada em Evidências , Feminino , Veias Hepáticas/diagnóstico por imagem , Veias Hepáticas/patologia , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade
5.
Br J Cancer ; 111(12): 2297-307, 2014 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-25349970

RESUMO

BACKGROUND: Folate receptor 1 (FOLR1) is expressed in the majority of ovarian carcinomas (OvCa), making it an attractive target for therapy. However, clinical trials testing anti-FOLR1 therapies in OvCa show mixed results and require better understanding of the prognostic relevance of FOLR1 expression. We conducted a large study evaluating FOLR1 expression with survival in different histological types of OvCa. METHODS: Tissue microarrays composed of tumour samples from 2801 patients in the Ovarian Tumour Tissue Analysis (OTTA) consortium were assessed for FOLR1 expression by centralised immunohistochemistry. We estimated associations for overall (OS) and progression-free (PFS) survival using adjusted Cox regression models. High-grade serous ovarian carcinomas (HGSC) from The Cancer Genome Atlas (TCGA) were evaluated independently for association between FOLR1 mRNA upregulation and survival. RESULTS: FOLR1 expression ranged from 76% in HGSC to 11% in mucinous carcinomas in OTTA. For HGSC, the association between FOLR1 expression and OS changed significantly during the years following diagnosis in OTTA (Pinteraction=0.01, N=1422) and TCGA (Pinteraction=0.01, N=485). In OTTA, particularly for FIGO stage I/II tumours, patients with FOLR1-positive HGSC showed increased OS during the first 2 years only (hazard ratio=0.44, 95% confidence interval=0.20-0.96) and patients with FOLR1-positive clear cell carcinomas (CCC) showed decreased PFS independent of follow-up time (HR=1.89, 95% CI=1.10-3.25, N=259). In TCGA, FOLR1 mRNA upregulation in HGSC was also associated with increased OS during the first 2 years following diagnosis irrespective of tumour stage (HR: 0.48, 95% CI: 0.25-0.94). CONCLUSIONS: FOLR1-positive HGSC tumours were associated with an increased OS in the first 2 years following diagnosis. Patients with FOLR1-negative, poor prognosis HGSC would be unlikely to benefit from anti-FOLR1 therapies. In contrast, a decreased PFS interval was observed for FOLR1-positive CCC. The clinical efficacy of FOLR1-targeted interventions should therefore be evaluated according to histology, stage and time following diagnosis.


Assuntos
Biomarcadores Tumorais/biossíntese , Receptor 1 de Folato/biossíntese , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/metabolismo , Carcinoma Epitelial do Ovário , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Análise de Sobrevida , Análise Serial de Tecidos
6.
Ultraschall Med ; 35(1): 44-50, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24510459

RESUMO

PURPOSE: To evaluate the diagnostic value of acoustic radiation force impulse (ARFI) and high-frequency ultrasound of the liver surface, using histology as a gold standard for the diagnosis of compensated liver cirrhosis. MATERIALS AND METHODS: 73 patients without ascites undergoing liver biopsy were included in the study. The left and right liver lobes were examined with ARFI and high-frequency ultrasound. Liver surface irregularity was quantified using image analysis software to calculate the difference between the real surface and the approximated physiological surface through a 20 mm standardized line. RESULTS: There is a significant difference between cirrhotic and non-cirrhotic patients for both quantified liver surface (QLS) and ARFI (p < 0.001). The mean values for QLS of the left lobe were 0.71 ± 0.24 mm and 1.17 ±â€Š0.80 mm, of the right lobe 0.56 ±â€Š0.26 mm and 0.87 ±â€Š0.26 mm for non-cirrhotic and cirrhotic patients, respectively. The mean values of ARFI measurements of the left lobe were 2.04 ±â€Š0.76 m/s and 2.85 ±â€Š0.81 m/s, of the right lobe 1.65 ±â€Š0.61 m/s and 3.02 ±â€Š0.77 m/s for non-cirrhotic and cirrhotic patients, respectively. Diagnostic accuracy (AUROC) was 0.78/0.80 for QLS and 0.77/0.91 for ARFI of the left/right lobe, respectively. ARFI of the right lobe is significantly better than ARFI of the left (p = 0.023) or QLS of the left (p = 0.025)/right (p = 0.046) lobe of the liver. CONCLUSION: Assessment of liver surface irregularity by high-frequency ultrasound (QLS) is a useful diagnostic test for the assessment of compensated liver cirrhosis. ARFI of the right liver lobe is significantly better than high-frequency ultrasound (QLS of the left/right lobe of the liver) and ARFI of the left lobe of the liver.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Cirrose Hepática/diagnóstico por imagem , Fígado/diagnóstico por imagem , Adulto , Idoso , Biópsia , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Fígado/patologia , Cirrose Hepática/patologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Valores de Referência , Sensibilidade e Especificidade , Software
8.
J Neurosurg Sci ; 55(3): 179-87, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21968582

RESUMO

AIM: Electrophysiological monitoring (EM) is still controversial in the prediction of outcome after subarachnoid hemorrhage (SAH). The absence of evoked potentials (EP) is a good predictor for unfavorable, whereas the prediction of favorable outcome may be less useful. Aim of this study was to evaluate, if multimodal EM provides significant information about the patients' outcome or if this method might be dispensable. METHODS: Multimodal EP data were recorded sequentially in 51 SAH-patients. The following data were recorded: World Federation of Neurological Surgeons (WFNS-) grade, Fisher grading score, endovascular versus neurosurgical treatment, aneurysm location and clinical outcome according to the Glasgow Outcome Scale (GOS). Multimodal electrophysiological monitoring included median nerve somatosensory evoked potential (M-SSEP), tibial nerve somatosensory evoked potential (T-SSEP), flash-visual evoked potential (f-VEP), brainstem auditory evoked potential (BAEP) and central conduction time (CCT) of M-SSEP. EP data were recorded sequentially; the first and last studies were evaluated. RESULTS: No correlation was found between initial and last M-SSEP, T-SSEP, BAEP and initial f-VEP and the patients' outcome. An 'unfavorable' outcome was in conjunction with an initial delayed CCT (>6 ms, P=0.03) and the final f-VEP correlated well with the patients' outcome (P=0.03). CONCLUSION: In conclusion, neither T-SSEP, f-VEP, BAEP nor CCT can be used as valid predictor for outcome after SAH. The patient's initial clinical grading still provides the only satisfying predictor, independent of the patient's clinical course.


Assuntos
Cuidados Críticos/métodos , Potenciais Somatossensoriais Evocados , Potenciais Evocados Visuais , Monitorização Fisiológica/métodos , Hemorragia Subaracnóidea/diagnóstico , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Índice de Gravidade de Doença , Hemorragia Subaracnóidea/terapia , Resultado do Tratamento , Adulto Jovem
9.
Minim Invasive Neurosurg ; 54(2): 55-60, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21523649

RESUMO

BACKGROUND: Tumors originating from or involving the petrous apex are considered to be an operative challenge due to their deep location and close relationship to critical neural and vascular structures. Extensive skull base approaches have been developed to deal with these lesions. The purpose of this study is to review an institutional series of 57 petrous apex tumors, to report our operative experiences and to address the usefulness and limits of standard approaches. MATERIAL AND METHODS: 57 patients (22 men, 35 women) with petrous apex tumors were treated microsurgically. We analyzed the type of surgical approach, histological diagnoses, pre- and postoperative clinical findings, diagnostic imaging and surgery-associated complications. RESULTS: According to the location and its predominant extension, a retromastoid approach (n=27), subtemporal approach (n=18), subtemporal/anterosigmoid approach (n=5), transnasal-transsphenoidal approach (n=2), pterional approach (n=2) or a subtemporal/retrosigmoid approach, biphasic approach (subtemporal and pterional), transmastoidal approach (n=1 each) was chosen. In the majority of cases, histological analysis revealed a meningeoma (n=31) or neurinoma (n=7). A total tumor resection was accomplished in 37 patients (64.9%). New permanent neurological deficits, mainly cranial nerve palsies, were found in 18 (31.6%), transient deficits in 5 patients (9.6%). Postoperative improvements of neurological deficits were observed in 17 patients (29.8%), and the neurological status remained unchanged in 17 patients (32.7%). CONCLUSION: Complete resection of petrous apex tumors using standard neurosurgical approaches without permanent surgery-associated neurological deficits is achievable in the majority of cases.


Assuntos
Meningioma/cirurgia , Neurilemoma/cirurgia , Osso Petroso/cirurgia , Neoplasias Cranianas/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico por imagem , Meningioma/patologia , Pessoa de Meia-Idade , Neurilemoma/diagnóstico por imagem , Neurilemoma/patologia , Procedimentos Neurocirúrgicos , Osso Petroso/diagnóstico por imagem , Osso Petroso/patologia , Radiografia , Estudos Retrospectivos , Neoplasias Cranianas/diagnóstico por imagem , Neoplasias Cranianas/patologia , Resultado do Tratamento
10.
Minim Invasive Neurosurg ; 53(2): 74-6, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20533138

RESUMO

INTRODUCTION: An intracranial plasmacytoma is a rare form, which can involve the calvarium, dura or the cranial base. Only few case reports describe the manifestation of plasmacytoma of the skull base with affection of visual acuity. CASE REPORT: We describe the case of a 43-year-old woman, presenting with an acute unilateral loss of vision. The presumption diagnosis was retrobulbar neuritis as first manifestation of multiple sclerosis. MR imaging disclosed a tumour in the left orbital region and a meningioma was suspected. After complete resection with decompression of the optic nerve, the neuropathological examination revealed a lambda positive plasmacytoma. Additional work-up disclosed an involvement of multiple vertebral bodies. Due to the diagnosis of multiple myeloma, oncological therapy had been initiated. CONCLUSION: Skull base plasmacytoma is a rare disease. Solitary lesions causing neurological deficits should be treated aggressively including surgery for histological diagnosis and decompression of neural structures. Prognosis and further therapy depends on the systemic stage of disease, which has to be defined by diagnostic work-up.


Assuntos
Cegueira/etiologia , Mieloma Múltiplo/diagnóstico , Neoplasias Orbitárias/diagnóstico , Neoplasias da Base do Crânio/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Mieloma Múltiplo/complicações , Neoplasias Orbitárias/complicações , Neoplasias da Base do Crânio/complicações
11.
Tijdschr Psychiatr ; 51(7): 433-42, 2009.
Artigo em Holandês | MEDLINE | ID: mdl-19609849

RESUMO

Psychiatrists today feel they are pulled between two schools of thought: on the one hand there is the theory which is based mainly on neuroscientific research, on the other hand there is the theory which puts more emphasis on the narrative character of psychiatric illness. In this article we will overlook this dichotomy and concentrate on psychiatry as a unitas multiplex, based on the foundations of both schools of thought. Both the scientific method and the phenomenological approach play an essential role in medical practice. Heidegger's thinking in the Zollikon Seminars will serve to develop a methodological consciousness.


Assuntos
Relações Médico-Paciente , Psiquiatria , Teoria Psicanalítica , Medicina Baseada em Evidências , Humanos , Psicanálise
12.
Tijdschr Psychiatr ; 50(2): 83-8, 2008.
Artigo em Holandês | MEDLINE | ID: mdl-18264898

RESUMO

BACKGROUND: Up till now research into dissociation has paid little attention to the relationship between current stress and family variables on the one hand and dissociative phenomena on the other hand. By contrast, however, many studies have investigated the link between traumatic experiences in the past and dissociative phenomena. AIM: To investigate, in a clinical population, whether dissociation is linked to current stress (within and outside the family) and to traumatic experiences in the past. METHOD: Dissociation was predicted on the basis of current stress (within and outside the family) and trauma by means of a multiple regression conducted on a population of patients with an eating disorder. RESULTS: Results indicated a clear link between current stress and dissociation. Patients with particularly high dissociation scores reported significantly more stress both on the measures of current stress and on the list of trauma. CONCLUSION: Dissociation is associated with stressful experiences, but not only with sexual trauma. Dissociation is also linked to stress experienced in current living conditions. Therefore the simple model that links dissociative experiences directly with trauma needs to be revised. This finding demonstrates that more attention should be given to stress factors in the treatment of dissociative phenomena.


Assuntos
Transtornos Dissociativos/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Estresse Psicológico , Ferimentos e Lesões/psicologia , Adolescente , Adulto , Transtornos Dissociativos/epidemiologia , Transtornos Dissociativos/etiologia , Feminino , Humanos , Masculino , Teoria Psicanalítica
13.
Histol Histopathol ; 33(8): 871-886, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29616745

RESUMO

AIMS: Mast cells (MC) and dendritic cells (DC) have immune modulatory function and can influence T-cell activity. Both cell types have been found in atherosclerotic plaques and are thought to play an important role for plaque stability. Compared to matched segments of the non-renal population, patients with chronic kidney disease (CKD) show a more pronounced and more aggressive course of atherosclerosis with higher plaque calcification and significantly higher complications rates. It was the aim of this study to analyze the number and localization of MCs and DCs, macrophages, T- and B-cells as well as the expression of markers of inflammation such as CRP and NFκB in calcified and non-calcified atherosclerotic plaques of patients with CKD and control patients. METHODS: Fifty coronary atherosclerotic plaques from patients with endstage CKD (CKD, n=25) and control (n=25) patients were categorized according to the Stary classification and investigated using immunohistochemistry (markers for MC, DC, T, B, macrophage and NFκB). Expression was analyzed separately for the complete plaque area as well as for the different plaque subregions and correlations were analyzed. RESULTS: We found only very few DCs and MCs per lesion area with slightly increased numbers in calcified plaques. MCs per plaque area were significantly more frequent in CKD than in control patients and this was independent of plaque calcification. MCs were most frequently found in the shoulder and basis of the plaque. DCs per plaque area were significantly less in calcified plaques of CKD compared to control patients. In control, but not in CKD patients, DCs were significantly more frequent in calcified than in non-calcified plaques. Within the plaques DCs were similarly distributed between all 4 subregions. CONCLUSIONS: Coronary atherosclerotic plaques of CKD patients showed a significantly higher number of MCs whereas DCs were less frequent compared to control patients particularly if plaques were calcified. These findings might indicate a potential proinflammatory role of MCs, but not of DCs in atherosclerotic lesions of CKD patients, adding another characteristic of advanced atherosclerosis in these patients.


Assuntos
Doença da Artéria Coronariana/patologia , Vasos Coronários/patologia , Células Dendríticas/patologia , Mastócitos/patologia , Placa Aterosclerótica , Insuficiência Renal Crônica/complicações , Idoso , Linfócitos B/imunologia , Linfócitos B/patologia , Estudos de Casos e Controles , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/imunologia , Vasos Coronários/imunologia , Células Dendríticas/imunologia , Feminino , Humanos , Mediadores da Inflamação/análise , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Mastócitos/imunologia , Pessoa de Meia-Idade , Insuficiência Renal Crônica/diagnóstico , Índice de Gravidade de Doença , Linfócitos T/imunologia , Linfócitos T/patologia , Calcificação Vascular/patologia
14.
Placenta ; 62: 58-65, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29405968

RESUMO

INTRODUCTION: Preeclampsia is a hypertensive, gestational disease, which is still the leading cause of pregnancy related morbidity and mortality. The impairment of placental angiogenesis and vascularization is discussed to be of etiopathologic relevance. Deytrosination and tyrosination of α-tubulin is important for the stability and dynamics of microtubules. An increase of α-tubulin detyrosination leads to microtubule stabilization, which is an essential prerequisite for physiologic vascular tube morphogenesis during angiogenesis. So far, little is known about the specific localization of detyrosinated (detyr) and tyrosinated (tyr) tubulin in the placenta and its relevance for preeclampsia. METHODS: Placental expression of detyr- and tyr-tubulin was analyzed by immunohistochemistry, immunofluorescence and western blot. For western blot quantification we used biopsies from healthy placentas (n = 21) and placentas from pregnancies complicated with small for gestational age (n = 5), preeclampsia (n = 5) or both (n = 5). RESULTS: Specific placental localization of detyr-tubulin was detected in the fetal endothelial cells of the placenta. Villous and extravillous trophoblasts as well as villous stroma cells were tyr-tubulin positive. Detyr-tubulin protein expression was significantly decreased in placentas complicated by preeclampsia. CONCLUSIONS: In summary, we report an accumulation of detyr-tubulin in villous vessels of the placenta and a significantly reduced level of detyr-tubulin in placental biopsies of preeclampsia cases. The reduction of placental detyr-tubulin in preeclampsia could suggest a deficit in villous vascular plasticity and might be associated with the impaired arborization of the disease.


Assuntos
Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Processamento de Proteína Pós-Traducional/fisiologia , Tubulina (Proteína)/metabolismo , Tirosina/metabolismo , Vilosidades Coriônicas/metabolismo , Células Endoteliais/metabolismo , Feminino , Humanos , Recém-Nascido Pequeno para a Idade Gestacional , Microtúbulos/metabolismo , Gravidez , Células Estromais/metabolismo
15.
J Exp Clin Cancer Res ; 36(1): 165, 2017 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-29169400

RESUMO

BACKGROUND: Human placental development resembles tumorigenesis, due to the invasive and fusogenic potential of trophoblasts. However, these features are tightly controlled in trophoblasts. Disturbance of this spatial and temporal regulation is thought to contribute to the rare formation of choriocarcinomas. Promoter hypermethylation and loss of the tumor suppressor Retinoic acid receptor responder 1 (RARRES1) were shown to contribute to cancer progression. Our study investigated the epigenetic and transcriptional regulation of RARRES1 in healthy human placenta in comparison to choriocarcinoma cell lines and cases. METHODS: Three choriocarcinoma cell lines (Jeg-3, JAR and BeWo) were treated with three different retinoic acid derivates (Am580, Tazarotene and all-trans retinoic acid) and 5-aza-2'-deoxycytidine. We analyzed RARRES1 promoter methylation by pyrosequencing and performed realtime-PCR quantification to determine RARRES1 expression in placental tissue and trophoblastic cell lines. Additionally, RARRES1 was stained in healthy placentas and in biopsies of choriocarcinoma cases (n = 10) as well as the first trimester trophoblast cell line Swan71 by immunofluorescence and immunohistochemistry. RESULTS: In the choriocarcinoma cell lines, RARRES1 expression could not be induced by sole retinoic acid treatment. Stimulation with 5-aza-2'-deoxycytidine significantly induced RARRES1 expression, which then could be further increased with Am580, Tazarotene and all-trans retinoic acid. In comparison to healthy placenta, choriocarcinoma cell lines showed a hypermethylation of the RARRES1 promoter, which correlated with a reduced RARRES1 expression. In concordance, RARRES1 protein expression was lost in choriocarcinoma tissue. Additionally, in the trophoblastic cell line Swan71, we found a significant induction of RARRES1 expression with increased cell density, during mitosis and in syncytial knots. CONCLUSIONS: Our findings showed that RARRES1 expression is absent in choriocarcinoma due to promoter methylation. Based on our analysis, we hypothesize that RARRES1 might exert tumor suppressive functions in multiple cellular processes (e.g. cell cycle regulation, adhesion, invasion and apoptosis).


Assuntos
Coriocarcinoma/genética , Metilação de DNA , Regulação para Baixo , Proteínas de Membrana/genética , Neoplasias Uterinas/genética , Linhagem Celular Tumoral , Coriocarcinoma/metabolismo , Progressão da Doença , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana/metabolismo , Gravidez , Regiões Promotoras Genéticas , Análise de Sequência de DNA , Neoplasias Uterinas/metabolismo
16.
Surg Endosc ; 20(12): 1897-903, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17024542

RESUMO

BACKGROUND: Infection of pancreatic necrosis (IPN) is strongly associated with sepsis and multiple organ dysfunction and is an absolute indication for surgery. Patients with IPN are critically ill at the time of surgery and may benefit from a minimally invasive approach with reduced surgical trauma. Recently, several minimally invasive necrosectomy techniques have been reported. However, the effects and potential dangers of a pneumoperitoneum in IPN cases are unknown. This study aimed to determine the effects of a pneumoperitoneum on systemic cytokine levels, bacterial translocation, and systemic organ complications in a rat model of IPN. METHODS: For this study, IPN was induced in Wistar rats using retrograde intraductal infusion of 3% taurocholate. After 8 h, the animals were subjected to either laparoscopy (pneumoperitoneum at 8 mmHg) or laparotomy for 1 h and killed after 1 or 3 h. Severe acute pancreatitis with IPN was proved by serum amylase and lipase, histology, tissue activity of myeloperoxidase (MPO), and bacteriology. Systemic levels for interleukin-10 (IL-10), IL-6, tumor necrosis factor-alpha (TNF-alpha), and lipopolysaccarides were determined by enzyme-linked immunoassay (ELISA). Systemic organ damage and dysfunction were evaluated using MPO activity (lung), serum creatinine (kidney), and serum aminotransferases (liver). RESULTS: Necrotizing pancreatitis developed in all the animals. Most of the animals (85%) had proven infected necrosis. Elevated cytokine levels and deteriorated organ parameters demonstrated systemic inflammation and organ failure. Although there was a tendency toward a higher level of proinflammatory cytokines after laparotomy, there were no significant differences between laparotomy and laparoscopy. Furthermore, these alterations were not accompanied by any differences in bacterial translocation (lipopolysaccharides), systemic organ damage, or mortality between laparoscopy and laparotomy. CONCLUSION: In the current model of infected pancreatic necrosis, a pneumoperitoneum did not result in increased cytokine release or bacterial translocation. However, the putative advantage of less surgical trauma with the laparoscopic approach did not play a significant role in the setting of severe acute pancreatitis with IPN.


Assuntos
Bactérias Aeróbias/fisiologia , Infecções Bacterianas/microbiologia , Translocação Bacteriana , Citocinas/sangue , Insuficiência de Múltiplos Órgãos/sangue , Pancreatite Necrosante Aguda/cirurgia , Pneumoperitônio Artificial/métodos , Animais , Bactérias Aeróbias/isolamento & purificação , Infecções Bacterianas/sangue , Infecções Bacterianas/complicações , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/microbiologia , Pancreatite Necrosante Aguda/sangue , Pancreatite Necrosante Aguda/complicações , Ratos , Ratos Wistar , Índice de Gravidade de Doença , Resultado do Tratamento
17.
Geburtshilfe Frauenheilkd ; 76(1): 59-64, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26855442

RESUMO

Introduction: Stereotactically-guided core needle biopsies (CNB) of breast tumours allow histological examination of the tumour without surgery. Touch imprint cytology (TIC) of CNB promises to be useful in providing same-day diagnosis for counselling purposes and for planning future surgery. Having addressed the issue of accuracy of immediate microscopic evaluation of TIC, we wanted to re-examine the usefulness of this procedure in light of the present health care climate of cost containment by incorporating the surgical 15-year follow-up data and outcome. Patients and Methods: From January until December 1996 we performed TIC in core needle biopsies of 173 breast tumours in 169 patients, consisting of 122 malignant and 51 benign tumours. Histology of core needle biopsies was proven by surgical histology in all malignant and in 5 benign tumours. Surgical breast biopsy was not performed in 46 patients with 46 benign lesions, as the histological result from the core needle biopsy and the result of the TIC were in agreement with the suspected diagnosis from the complementary breast diagnostics. A 15-year follow-up of these patients followed in 2013 and follow-up data was collected from 40 women. Results: In the 15-year follow-up of the 40 benign lesions primarily confirmed using CNB and TIC, a diagnostic sensitivity, specificity, positive and negative predictive value and accuracy of 100 % was found. Conclusion: TIC and stereotactically guided CNB showed excellent long-term follow-up in patients with benign breast lesions. The use of TIC to complement CNB can therefore provide immediate cytological diagnosis of breast lesions.

18.
Geburtshilfe Frauenheilkd ; 75(1): 72-76, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25684789

RESUMO

Introduction: This study aimed to compare the accuracy of sonography versus digital breast tomosynthesis to locate intramammary marker clips placed under ultrasound guidance. Patients and Methods: Fifty patients with suspicion of breast cancer (lesion diameter less than 2 cm [cT1]) had ultrasound-guided core needle biopsy with placement of a marker clip in the center of the tumor. Intramammary marker clips were subsequently located with both sonography and digital breast tomosynthesis. Results: Sonography detected no dislocation of intrammammary marker clips in 42 of 50 patients (84 %); dislocation was reported in 8 patients (16 %) with a maximum dislocation of 7 mm along the x-, y- or z-axis. Digital breast tomosynthesis showed accurate placement without dislocation of the intramammary marker clip in 48 patients (96 %); 2 patients (4 %) had a maximum clip dislocation of 3 mm along the x-, y- or z-axis (p < 0.05). Conclusion: The use of digital breast tomosynthesis could improve the accuracy when locating intramammary marker clips compared to sonography and could, in future, be used to complement or even completely replace sonography.

19.
ASAIO J ; 42(5): M524-9, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8944934

RESUMO

The highest shear stresses in a dialysis system are expected to be found in the needle, where the largest velocity-diameter ratio appears. Shear is a known source of hemolysis and related patients' discomfort. To assess the magnitude of blood cell injury and the location of its sources, a finite element model is used to calculate three-dimensional velocities and shear stresses in peripheral dialysis needles, concentrically placed in a rigid wall fistula. The boundary conditions consist of time dependent in vivo measured pressures. Cell damage is computed for different cell tracks into the needle by means of Wurzinger's empirical formula, which expresses the hemoglobin (Hb) release as a function of shear stress and shearing time. Near the needle wall, velocities are low and shear stresses high, resulting in a significantly higher level of cell damage: 0.1% vs 0.001% in bulk flow for a mean flow of 91 ml/min into a 14G needle with a peak velocity of 220 cm/sec. The deviation from the classic Poiseuille velocity profile is shown. Less than 5% of the flow passes through this high damage path. A vortex at the inner side of the needle has a cumulative damage of 0.007% per 0.23 sec trip around the vortex.


Assuntos
Eritrócitos/fisiologia , Agulhas/efeitos adversos , Diálise Renal/efeitos adversos , Diálise Renal/instrumentação , Seringas/efeitos adversos , Velocidade do Fluxo Sanguíneo , Hemólise , Humanos , Modelos Biológicos , Pressão , Estresse Mecânico
20.
ASAIO J ; 46(5): 532-5, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11016501

RESUMO

An artificial lung is used during cardiopulmonary bypass to oxygenate blood and to control blood temperature. The pressure drop-flow rate characteristics of the membrane compartment in three hollow fiber membrane oxygenators were determined in vitro to characterize design features. Results are presented in a unique dimensionless relationship between Euler number, N(Eu) (ratio of pressure drop to kinetic energy), and Reynolds number, N(Re) (ratio of inertial to viscous forces), and are a function of the device porosity, epsilon, and a characteristic device length, xi, defined as the ratio of the mean blood path and manifold length: [equation in text]. This dimensionless approach allows us (1) to compare oxygenators independently, and (2) to relate water tests to blood.


Assuntos
Órgãos Artificiais , Pulmão , Ponte Cardiopulmonar , Humanos , Oxigenadores de Membrana , Análise de Regressão , Viscosidade
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