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1.
Nature ; 594(7863): 365-368, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34135524

RESUMO

Red supergiants are the most common final evolutionary stage of stars that have initial masses between 8 and 35 times that of the Sun1. During this stage, which lasts roughly 100,000 years1, red supergiants experience substantial mass loss. However, the mechanism for this mass loss is unknown2. Mass loss may affect the evolutionary path, collapse and future supernova light curve3 of a red supergiant, and its ultimate fate as either a neutron star or a black hole4. From November 2019 to March 2020, Betelgeuse-the second-closest red supergiant to Earth (roughly 220 parsecs, or 724 light years, away)5,6-experienced a historic dimming of its visible brightness. Usually having an apparent magnitude between 0.1 and 1.0, its visual brightness decreased to 1.614 ± 0.008 magnitudes around 7-13 February 20207-an event referred to as Betelgeuse's Great Dimming. Here we report high-angular-resolution observations showing that the southern hemisphere of Betelgeuse was ten times darker than usual in the visible spectrum during its Great Dimming. Observations and modelling support a scenario in which a dust clump formed recently in the vicinity of the star, owing to a local temperature decrease in a cool patch that appeared on the photosphere. The directly imaged brightness variations of Betelgeuse evolved on a timescale of weeks. Our findings suggest that a component of mass loss from red supergiants8 is inhomogeneous, linked to a very contrasted and rapidly changing photosphere.

2.
Eur J Clin Pharmacol ; 77(2): 189-195, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32926203

RESUMO

PURPOSE: Although more practical for use, the impact of ferric carboxymaltose (FCM) on the hospital budget is considerable, and intravenous iron sucrose complex (ISC) represents a cost-saving alternative for the management of iron deficiency anemia in patients during hospitalization. The Drug Committee decided to reserve FCM for day hospitalizations and contraindications to ISC, especially allergy. ISC was available for prescription for all other situations. METHODS: The impact of a multifaceted intervention promoting a switch from FCM to ISC was evaluated using an interrupted time series model with segmented regression analysis. The standardized rate of the dispensing of FCM, ISC, and oral iron by the hospital pharmacy, as well as the rate of the dispensing of packed red blood cells and the number of biological iron status measurements, was analyzed before and after the intervention. RESULTS: There was an immediate decrease in FCM consumption following the intervention, with a reduction of 88% (RR: 0.12 [CI95% 0.10 to 0.15]). Conversely, there was a large increase in ISC use (RR: 5.1 [CI95% 4.4 to 5.9]). We did not observe a prescription shift to packed red blood cells or oral iron after the intervention. The time series analysis showed the frequency of iron status testing to remain stable before and after. The direct savings for intravenous iron for 8 months were 187,417.54 €. CONCLUSION: Our intervention to lower the impact of intravenous iron therapy on the hospital budget was effective.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Compostos Férricos/administração & dosagem , Óxido de Ferro Sacarado/administração & dosagem , Hematínicos/administração & dosagem , Maltose/análogos & derivados , Serviço de Farmácia Hospitalar/organização & administração , Administração Oral , Anemia Ferropriva/sangue , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/economia , Redução de Custos/estatística & dados numéricos , Análise Custo-Benefício/organização & administração , Análise Custo-Benefício/estatística & dados numéricos , Sistemas de Apoio a Decisões Clínicas/economia , Sistemas de Apoio a Decisões Clínicas/organização & administração , Prescrições de Medicamentos/economia , Prescrições de Medicamentos/estatística & dados numéricos , Compostos Férricos/economia , Óxido de Ferro Sacarado/economia , França , Implementação de Plano de Saúde , Hematínicos/economia , Custos Hospitalares/estatística & dados numéricos , Hospitalização/economia , Humanos , Infusões Intravenosas/economia , Análise de Séries Temporais Interrompida , Ferro/sangue , Maltose/administração & dosagem , Maltose/economia , Serviço de Farmácia Hospitalar/economia , Serviço de Farmácia Hospitalar/estatística & dados numéricos , Avaliação de Programas e Projetos de Saúde , Resultado do Tratamento
3.
Phys Rev Lett ; 122(10): 101102, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30932663

RESUMO

During its orbit around the four million solar mass black hole Sagittarius A* the star S2 experiences significant changes in gravitational potential. We use this change of potential to test one part of the Einstein equivalence principle: the local position invariance (LPI). We study the dependency of different atomic transitions on the gravitational potential to give an upper limit on violations of the LPI. This is done by separately measuring the redshift from hydrogen and helium absorption lines in the stellar spectrum during its closest approach to the black hole. For this measurement we use radial velocity data from 2015 to 2018 and combine it with the gravitational potential at the position of S2, which is calculated from the precisely known orbit of S2 around the black hole. This results in a limit on a violation of the LPI of |ß_{He}-ß_{H}|=(2.4±5.1)×10^{-2}. The variation in potential that we probe with this measurement is six magnitudes larger than possible for measurements on Earth, and a factor of 10 larger than in experiments using white dwarfs. We are therefore testing the LPI in a regime where it has not been tested before.

4.
Acta Neuropathol ; 126(1): 123-35, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23400299

RESUMO

Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.


Assuntos
Hipófise/patologia , Neoplasias Hipofisárias/classificação , Neoplasias Hipofisárias/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Estudos de Casos e Controles , Intervalo Livre de Doença , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Hipófise/ultraestrutura , Neoplasias Hipofisárias/cirurgia , Prognóstico , Recidiva , Estudos Retrospectivos , Sensibilidade e Especificidade , Fatores Sexuais , Adulto Jovem
5.
Eur Spine J ; 22 Suppl 6: S957-64, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24048651

RESUMO

INTRODUCTION: We intended to prospectively evaluate the clinical and radiological results of lumbo-sacral fusion achieved by a combined approach, anterior then posterior. MATERIAL AND METHODS: 62 patients were consecutively treated at L5-S1, L4-L5 or L4-S1 for degenerative disc disease or low-grade isthmic spondylolisthesis by combined surgery. RESULTS: Mean operative time and blood loss were 209 min and 308 ml, respectively, including the two approaches. VAS, ODI and Roland-Morris scores significantly improved postoperatively at 1 year (p < 0.005) and fusion was obtained in all cases on the CT scan at 1-year follow-up. Segmental lordosis significantly improved postoperatively (p < 0.05) with a mean gain of 10.2° at L5-S1 and 5.5° at L4-L5. CONCLUSION: The combined procedure meets the requested criteria for a lumbar fusion in terms of clinical results, functional outcomes, fusion rates while restoring segmental lordosis and disc height. It cumulates the advantages of the anterior and posterior approach performed alone, especially for L5-S1.


Assuntos
Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Sacro/diagnóstico por imagem , Sacro/cirurgia , Fusão Vertebral/instrumentação , Fusão Vertebral/métodos , Adulto , Feminino , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/cirurgia , Lordose/diagnóstico por imagem , Lordose/cirurgia , Região Lombossacral/diagnóstico por imagem , Região Lombossacral/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Espondilolistese/diagnóstico por imagem , Espondilolistese/cirurgia , Resultado do Tratamento
6.
Eur J Orthop Surg Traumatol ; 23 Suppl 1: S15-9, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23689909

RESUMO

Prevention is particularly challenging in implant-associated bone and joint infection, as it could reduce the following: (1) the risk of infection in particular patient populations; (2) the risk associated with particular surgical procedures; and/or (3) the risk of infection with particular pathogen that has the ability to produce biofilm, such as staphylococci. As a consequence, it is crucial to identify: (1) host-related risk factors that may be involved in the acquisition of infection; (2) surgical procedures particularly at risk of infection; and (3) the different ways to target the most frequent pathogens involved in implant-associated spinal infection. In this article, we reviewed the data of the literature on the infection prevention in spine surgery.


Assuntos
Procedimentos Ortopédicos , Infecções Relacionadas à Prótese , Doenças da Coluna Vertebral/cirurgia , Antibioticoprofilaxia/métodos , Interações Hospedeiro-Patógeno , Humanos , Controle de Infecções , Procedimentos Ortopédicos/efeitos adversos , Procedimentos Ortopédicos/classificação , Procedimentos Ortopédicos/métodos , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/prevenção & controle , Medição de Risco , Fatores de Risco , Doenças da Coluna Vertebral/classificação , Doenças da Coluna Vertebral/etiologia , Coluna Vertebral/microbiologia , Coluna Vertebral/cirurgia , Staphylococcus/fisiologia
7.
Eur J Orthop Surg Traumatol ; 23 Suppl 1: S29-34, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23712673

RESUMO

The follow-up of patients with postoperative infection of the spine required a multidisciplinary teamwork under the guidance of the spine surgeon and the infectious disease (ID) specialist. During follow-up, the spine surgeon has to ensure the absence of neurological, mechanical and implant-related complications using clinical parameters and different imaging modalities. The ID physician has to give particular attention to antimicrobial efficacy and toxicity, especially during the first weeks when patients necessitate high-dose intravenous treatment.


Assuntos
Antibacterianos/uso terapêutico , Procedimentos Ortopédicos/efeitos adversos , Infecções Relacionadas à Prótese , Doenças da Coluna Vertebral/cirurgia , Infecção da Ferida Cirúrgica , Humanos , Imageamento por Ressonância Magnética , Monitorização Neurofisiológica/métodos , Equipe de Assistência ao Paciente/organização & administração , Período Pós-Operatório , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/fisiopatologia , Infecções Relacionadas à Prótese/prevenção & controle , Medição de Risco , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/microbiologia , Coluna Vertebral/fisiopatologia , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/fisiopatologia , Infecção da Ferida Cirúrgica/prevenção & controle , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
Nature ; 432(7016): 479-82, 2004 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-15565147

RESUMO

Our Solar System was formed from a cloud of gas and dust. Most of the dust mass is contained in amorphous silicates, yet crystalline silicates are abundant throughout the Solar System, reflecting the thermal and chemical alteration of solids during planet formation. (Even primitive bodies such as comets contain crystalline silicates.) Little is known about the evolution of the dust that forms Earth-like planets. Here we report spatially resolved detections and compositional analyses of these building blocks in the innermost two astronomical units of three proto-planetary disks. We find the dust in these regions to be highly crystallized, more so than any other dust observed in young stars until now. In addition, the outer region of one star has equal amounts of pyroxene and olivine, whereas the inner regions are dominated by olivine. The spectral shape of the inner-disk spectra shows surprising similarity with Solar System comets. Radial-mixing models naturally explain this resemblance as well as the gradient in chemical composition. Our observations imply that silicates crystallize before any terrestrial planets are formed, consistent with the composition of meteorites in the Solar System.

9.
Nature ; 429(6987): 47-9, 2004 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-15129274

RESUMO

Active galactic nuclei (AGNs) display many energetic phenomena--broad emission lines, X-rays, relativistic jets, radio lobes--originating from matter falling onto a supermassive black hole. It is widely accepted that orientation effects play a major role in explaining the observational appearance of AGNs. Seen from certain directions, circum-nuclear dust clouds would block our view of the central powerhouse. Indirect evidence suggests that the dust clouds form a parsec-sized torus-shaped distribution. This explanation, however, remains unproved, as even the largest telescopes have not been able to resolve the dust structures. Here we report interferometric mid-infrared observations that spatially resolve these structures in the galaxy NGC 1068. The observations reveal warm (320 K) dust in a structure 2.1 parsec thick and 3.4 parsec in diameter, surrounding a smaller hot structure. As such a configuration of dust clouds would collapse in a time much shorter than the active phase of the AGN, this observation requires a continual input of kinetic energy to the cloud system from a source coexistent with the AGN.

10.
Acta Anaesthesiol Scand ; 54(9): 1128-36, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20887415

RESUMO

BACKGROUND: Although a strategy of tidal volume (V(t)) reduction during the one-lung ventilation (OLV) period is advised in thoracic surgery, the influence of the pre-operative respiratory status on the tolerance of this strategy remains unknown. Therefore, the aim of this study was to compare the pulmonary function between chronic obstructive pulmonary disease (COPD) and healthy-lung patients during the operative and the post-operative period. METHODS: Forty-eight patients undergoing a planned lobectomy for cancer and presenting either a healthy lung function (n=24) or a moderate COPD stage (n=24) were ventilated without external positive end-expiratory pressure (PEEP) and received 9 ml/kg V(t) during the two-lung ventilation (TLV) period, secondary reduced to 6 ml/kg during the OLV period. Lung function was assessed by peroperative gas exchange, venous admixture, respiratory mechanical parameters and post-operative spirometric measurements. RESULTS: Although the PaO(2) was superior in the healthy-lung group during the TLV, once the OLV was established, no difference was observed between the two groups. Moreover, the PaO(2)/FiO(2) was proportionally more impaired in the healthy-lung group compared with the COPD group (50 ± 13 vs. 72 ± 19% of the baseline values after exclusion and 32 ± 15 vs. 51 ± 25% after the thoracotomy, P<0.05 for each) as well as the venous admixture. In the post-operative period, a higher decrease was observed in the healthy-lung group for the forced vital capacity and the forced expiratory volume. CONCLUSIONS: Reducing V(t) to 6 ml/kg without the adjunction of external PEEP during OLV is associated with better preservation of lung function in the case of moderate COPD than in the case of healthy-lung status.


Assuntos
Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ventilação Pulmonar , Respiração Artificial/métodos , Volume de Ventilação Pulmonar , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Respiração com Pressão Positiva , Estudos Prospectivos , Espirometria
11.
Opt Express ; 17(3): 1925-34, 2009 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-19189023

RESUMO

The direct imaging and characterization of Earth-like planets is among the most sought-after prizes in contemporary astrophysics, however current optical instrumentation delivers insufficient dynamic range to overcome the vast contrast differential between the planet and its host star. New opportunities are offered by coherent single mode fibers, whose technological development has been motivated by the needs of the telecom industry in the near infrared. This paper presents a new vision for an instrument using coherent waveguides to remap the pupil geometry of the telescope. It would (i) inject the full pupil of the telescope into an array of single mode fibers, (ii) rearrange the pupil so fringes can be accurately measured, and (iii) permit image reconstruction so that atmospheric blurring can be totally removed. Here we present a laboratory experiment whose goal was to validate the theoretical concepts underpinning our proposed method. We successfully confirmed that we can retrieve the image of a simulated astrophysical object (in this case a binary star) though a pupil remapping instrument using single mode fibers.

12.
Cogn Process ; 10(4): 343-53, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19277746

RESUMO

The theory that human cognition proceeds through mental simulations, if true, would provide a parsimonious explanation of how the mechanisms of reasoning and problem solving integrate with and develop from mechanisms underlying forms of cognition that occur earlier in evolution and development. However, questions remain about whether simulation mechanisms are powerful enough to exhibit human-level reasoning and inference. In order to investigate this issue, we show that it is possible to characterize some of the most powerful modern artificial intelligence algorithms for logical and probabilistic inference as methods of simulating alternate states of the world. We show that a set of specific human perceptual mechanisms, even if not implemented using mechanisms described in artificial intelligence, can nevertheless perform the same operations as those algorithms. Although this result does not demonstrate that simulation theory is true, it does show that whatever mechanisms underlie perception have at least as much power to explain non-perceptual human reasoning and problem solving as some of the most powerful known algorithms.


Assuntos
Inteligência Artificial , Cognição/fisiologia , Modelos Psicológicos , Percepção/fisiologia , Algoritmos , Formação de Conceito/fisiologia , Tomada de Decisões/fisiologia , Humanos , Lógica , Resolução de Problemas/fisiologia
13.
J Clin Invest ; 99(6): 1173-8, 1997 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-9077524

RESUMO

Astrocytomas are among the most common brain tumors that are usually fatal in their malignant form. They appear to progress without significant impedance from the immune system, despite the presence of intratumoral T cell infiltration. To date, this has been thought to be the result of T cell immunosuppression induced by astrocytoma-derived cytokines. Here, we propose that cell contact-mediated events also play a role, since we demonstrate the in vivo expression of Fas ligand (FasL/CD95L) by human astrocytoma and the efficient killing of Fas-bearing cells by astrocytoma lines in vitro and by tumor cells ex vivo. Functional FasL is expressed by human, mouse, and rat astrocytoma and hence may be a general feature of this nonlymphoid tumor. In the brain, astrocytoma cells can potentially deliver a death signal to Fas+ cells which include infiltrating leukocytes and, paradoxically, astrocytoma cells themselves. The expression of FasL by astrocytoma cells may extend the processes that are postulated to occur in normal brain to maintain immune privilege, since we also show FasL expression by neurons. Overall, our findings suggest that FasL-induced apoptosis by astrocytoma cells may play a significant role in both immunosuppression and the regulation of tumor growth within the central nervous system.


Assuntos
Astrocitoma/imunologia , Neoplasias Encefálicas/imunologia , Encéfalo/imunologia , Glicoproteínas de Membrana/biossíntese , Receptor fas/metabolismo , Animais , Astrocitoma/metabolismo , Astrocitoma/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Testes Imunológicos de Citotoxicidade , Proteína Ligante Fas , Humanos , Ligantes , Glicoproteínas de Membrana/fisiologia , Camundongos , Ratos , Células Tumorais Cultivadas
14.
Ann Endocrinol (Paris) ; 68(1): 28-33, 2007 Feb.
Artigo em Francês | MEDLINE | ID: mdl-17306208

RESUMO

Nelson's syndrome was defined in 1958 as the association of an expanding pituitary tumor with high ACTH secretion after bilateral adrenalectomy for Cushing's disease. Pituitary MRI and ACTH measurements led to the definition of Nelson's syndrome as the proliferation of a corticotrophic microadenoma or an aggressive and highly proliferative tumor residue induced by the decreased glucocorticoid inhibition after bilateral adrenalectomy. Now, the problem is not the definition of Nelson's syndrome but rather the identification of markers predictive of tumor growth. Based on a typical case and a review of the literature, we point out some predictive markers of tumor growth after bilateral adrenalectomy: young age at diagnosis, presence of tumor residue on pituitary MRI before adrenalectomy, markers of tumor aggressiveness (Ki-67>3%, mitoses, nuclear PTTG) and increase of ACTH levels during the first months following adrenalectomy.


Assuntos
Adenoma/fisiopatologia , Síndrome de Nelson/fisiopatologia , Neoplasias Hipofisárias/fisiopatologia , Adenoma/diagnóstico , Hormônio Adrenocorticotrópico/análise , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Síndrome de Nelson/diagnóstico , Hipófise/patologia , Neoplasias Hipofisárias/diagnóstico
15.
J West Afr Coll Surg ; 7(3): 116-123, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-30525006

RESUMO

We present a middle-aged man with features of diabetes insipidus, visual and mental impairments as a result of metastases from bronchogenic carcinoma. This case is being presented because it is uncommon; high index of suspicion and the relevant imaging techniques are required for diagnosis. Surgical resection of the pituitary secondaries with post-operative chemo-radiation brought resolution of symptoms. CONCLUSION: In conclusion, hypothalamic metastases are uncommon and are often associated with compression of the pituitary gland and optic chiasma leading to diabetes insipidus, visual impairment and mental defects. MRI for diagnosis and surgical resection followed with chemoradiation lead to improvement of symptoms but mortality is high.

16.
Neurochirurgie ; 63(5): 381-390, 2017 Nov.
Artigo em Francês | MEDLINE | ID: mdl-28527519

RESUMO

OBJECTIVES: Intramedullary gliomas are rare tumors accounting for less than 4% of all primary central nervous system tumors. The aims of this retrospective multicenter study were to assess their natural outcome as well as management. METHODS AND MATERIALS: We studied 332 patients from 1984 to 2011. Histopathological examination revealed 72% ependymomas (94% were low grade tumors), 24% astrocytomas (29% were high grade tumors), 2.4% mixed gliomas and 1.7% oligodendrogliomas. RESULTS: The mean age at diagnosis was 42.4 years for ependymomas, with male predominance, versus 39.6 years for astrocytomas. Pain was the most common initial presentation. In 20% of cases, astrocytomas were biopsied alone, but more than 80% of ependymomas had surgical resection. Radiotherapy and chemotherapy were reserved for malignant tumors, especially if they were ependymomas. The 5-year survival rate was 76.8% for astrocytomas and 94.5% for ependymomas. Histology, functional status prior to surgery, and tumor grade are among the prognostic factors. CONCLUSION: Our study showed that surgical treatment of gliomas is well codified, at least for ependymomas, but adjuvant treatment continues to play a marginal role in the management even in astrocytomas, which are infiltrative tumors.


Assuntos
Glioma/terapia , Neoplasias da Medula Espinal/terapia , Adulto , Feminino , Glioma/diagnóstico , Glioma/patologia , Humanos , Masculino , Estudos Retrospectivos , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/patologia
17.
Cancer Res ; 61(5): 2047-54, 2001 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-11280765

RESUMO

HLA-A2+ melanoma patients develop naturally a strong CD8+ T cell response to a self-peptide derived from Melan-A. Here, we have used HLA-A2/peptide tetramers to isolate Melan-A-specific T cells from tumor-infiltrated lymph nodes of two HLA-A2+ melanoma patients and analyzed their TCR beta chain V segment and complementarity determining region 3 length and sequence. We found a broad diversity in Melan-A-specific immune T-cell receptor (TCR) repertoires in terms of both TCR beta chain variable gene segment usage and clonal composition. In addition, immune TCR repertoires selected in the patients were not overlapping. In contrast to previously characterized CD8+ T-cell responses to viral infections, this study provides evidence against usage of highly restricted TCR repertoire in the natural response to a self-differentiation tumor antigen.


Assuntos
Antígenos de Neoplasias/imunologia , Melanoma/imunologia , Proteínas de Neoplasias/imunologia , Fragmentos de Peptídeos/imunologia , Linfócitos T Citotóxicos/imunologia , Sequência de Aminoácidos , Sequência de Bases , Regiões Determinantes de Complementaridade/imunologia , Epitopos de Linfócito T/imunologia , Antígeno HLA-A2/imunologia , Humanos , Epitopos Imunodominantes/imunologia , Região Variável de Imunoglobulina/imunologia , Linfonodos/imunologia , Linfonodos/patologia , Antígeno MART-1 , Dados de Sequência Molecular , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia
18.
Acta Neurochir (Wien) ; 147(7): 751-7; discussion 757-8, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15971099

RESUMO

BACKGROUND: Prolactinomas usually exhibit a benign course and can be safely and effectively managed by dopamine agonists (DA). However, some are locally invasive and may show resistance to DA therapy, and the management of such cases remains controversial. The aim of the present study was to determine whether histological features and markers of cell proliferation correlated to the clinical behaviour of prolactinomas and with DA resistance. METHOD: This retrospective study included 74 cases (36 men and 38 women) who had monohormonal prolactinomas removed by transsphenoidal surgery. The prolactinomas were categorized on the basis of tumour size (48 macroadenomas), invasion of the cavernous sinus (n = 31), and resistance to bromocriptine (BRC) therapy (n = 14). Group 1 consisted of non-invasive microprolactinomas (n = 24), group 2 of non-invasive macroprolactinomas (n = 19), group 3 of invasive non-BRC-resistant tumours (n = 19), and group 4 of invasive BRC-resistant tumours (n = 12). The later group included one case of carcinoma with bone and lung metastases. Seven additional parameters were studied, these being age, sex, basal prolactin (PRL) levels, the Ki-67 and PCNA labelling indices (LI), mitotic count, and cellular atypia. FINDINGS: Age and preoperative PRL levels did not correlate to the histological parameters studied. Tumour size and invasion were related to cellular atypia and the Ki-67 LI. BRC-resistant tumours were more frequently invasive (12/14) than BRC-responsive tumours (11/30; p = 0.002) and were more frequent in men than in women (33 versus 5%; p = 0.003). BRC-resistant tumours had a higher Ki-67 LI and mitotic count (4.2+/-2.0% and 4+/-1, respectively) than other tumours (0.7+/-0.2% and 1+/-0, respectively; p<0.05). The strongest correlations with tumoural staging were seen with male sex and high mitotic activity. Six out of the 12 invasive BRC-resistant macroprolactinomas, including the PRL secreting carcinoma, exhibited histological features of aggressiveness (a mitotic count >/=3 [i.e. in the fourth quartile] and/or a high Ki-67 LI and cellular atypia). CONCLUSIONS: In this surgical retrospective series, histological signs of aggressiveness are present in 50% of invasive and BRC-resistant prolactinomas, which are more frequent in men than in women. This fits with the behaviour of BRC-resistant prolactinomas, which can continue to grow despite DA treatment. These findings justify the long-term follow up of these tumours, and the use of surgery and/or radiotherapy if there is concern about the control of tumour growth.


Assuntos
Bromocriptina/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Neoplasias Hipofisárias/cirurgia , Prolactinoma/cirurgia , Adulto , Idoso , Bromocriptina/efeitos adversos , Agonistas de Dopamina/efeitos adversos , Resistência a Medicamentos , Feminino , Humanos , Hipofisectomia , Antígeno Ki-67/análise , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Hipófise/patologia , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/patologia , Prolactinoma/diagnóstico , Prolactinoma/patologia , Estudos Retrospectivos , Fatores Sexuais
19.
Ann Fr Anesth Reanim ; 24(4): 355-60, 2005 Apr.
Artigo em Francês | MEDLINE | ID: mdl-15826785

RESUMO

OBJECTIVE: Prospective analysis of endovascular management of traumatic isthmic rupture with second generation stent grafts. STUDY DESIGN: Prospective analysis and follow-up. PATIENTS: Ten consecutive multiple injured patients presenting an acute isthmic traumatic rupture who underwent an endovascular repair with second generation stent grafts. METHODS AND RESULTS: The aortic injury was diagnosed by spiral computed tomography scan. The appropriate time to repair was decided according to multidisciplinary decision after analysis of associated injuries status and mediastinal lesions evolution. Endovascular repair was successfully completed in all patients under general anaesthesia without requirement of haemodynamic manipulations. Despite a prolonged length of stay related to associated injuries, all patients were discharged from hospital without migration of devices or complication related to the endovascular procedure. After a 20 months follow-up (range 6 - 38 months), all patients were alive with a satisfactory CT scan analysis. CONCLUSION: The immediate availability of the second generation of stents-grafts allowed the endovascular treatment of isthmic rupture without haemodynamic manipulations or massive heparinization. The analysis of this selected series reinforces the interest of this non-invasive technique for anaesthetists especially in polytraumatized patients.


Assuntos
Ruptura Aórtica/cirurgia , Stents , Procedimentos Cirúrgicos Vasculares , Adulto , Ruptura Aórtica/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/cirurgia , Estudos Prospectivos , Tomografia Computadorizada por Raios X
20.
J Clin Endocrinol Metab ; 58(2): 242-9, 1984 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-6319445

RESUMO

A beta-endorphin (beta END)-containing pituitary adenoma was demonstrated by immunocytochemical, biochemical, and ultrastructural methods in a 43-yr-old man who had impotence, slight testicular atrophy, and an enlarged sella turcica (grade II0), but no manifestations of Cushing's disease. Preoperative hormone data revealed hyperprolactinemia (97 ng/ml), low plasma cortisol levels without circadian rhythm, undetectable plasma ACTH, and normal plasma FSH and LH levels, with an impaired response to LRH. After hypophysectomy, these hormone levels normalized and responded normally to dynamic tests. Immunocytochemically, 30% of the tumor cells reacted only with beta END antiserum. beta END immunoreactivity was the only component revealed by RIA and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A characteristic ultrastructural aspect is also described. These findings demonstrate dissociation in the secretion of the proopiomelanocortin-derived peptides and suggest a relationship between hyperprolactinemia and tumor secretion of beta END.


Assuntos
Adenoma/análise , Endorfinas/análise , Neoplasias Hipofisárias/análise , Adenoma/patologia , Adenoma/ultraestrutura , Adulto , Eletroforese em Gel de Poliacrilamida , Imunofluorescência , Humanos , Masculino , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/ultraestrutura , Radioimunoensaio , beta-Endorfina
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