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1.
Intensive Care Med Exp ; 11(1): 26, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37150798

RESUMO

Therapeutic plasma exchange (TPE) is a therapeutic intervention that separates plasma from blood cells to remove pathological factors or to replenish deficient factors. The use of TPE is increasing over the last decades. However, despite a good theoretical rationale and biological plausibility for TPE as a therapy for numerous diseases or syndromes associated with critical illness, TPE in the intensive care unit (ICU) setting has not been studied extensively. A group of eighteen experts around the globe from different clinical backgrounds used a modified Delphi method to phrase key research questions related to "TPE in the critically ill patient". These questions focused on: (1) the pathophysiological role of the removal and replacement process, (2) optimal timing of treatment, (3) dosing and treatment regimes, (4) risk-benefit assumptions and (5) novel indications in need of exploration. For all five topics, the current understanding as well as gaps in knowledge and future directions were assessed. The content should stimulate future research in the field and novel clinical applications.

2.
Front Immunol ; 13: 1069360, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36569885

RESUMO

Hyperviscosity syndrome (HVS) is a rare complication of newly diagnosed multiple myeloma (NDMM) related to high tumour burden. Studies about the prognosis of HVS in modern-era therapy for NDMM are missing. We investigated a retrospective cohort study of NDMM with HVS between 2011-2021. Thirty-nine NDMM patients with HVS were included. HVS presentation was heterogeneous, with asymptomatic, mild, and neurological forms in 23%, 59%, and 18% of cases, respectively. No thrombosis or major bleeding was observed. Therapeutic plasma exchanges were used in 92% of patients, which were effective and well tolerated. No rebound effect was observed. All patients except one had at least one CRAB criterion. Most of the patients received bortezomib and high-dose steroids (95%) associated with an immunomodulatory drug (43%) or alkylating agents (42%). HVS in NDMM patients had dismal overall survival matched to multiple myeloma patient controls (without HVS) in our center (median: 3.6 vs. 7.7 years, p=0.01), as confirmed by multivariate analysis. Early deaths (in the first two months) occurred in 21% of older patients (>65 years). HVS in NDMM patients is a rare but life-threatening complication associated with high lethality in older patients and be a potential dismal prognosis factor in the modern treatment era.


Assuntos
Doenças Hematológicas , Mieloma Múltiplo , Humanos , Idoso , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos , Prognóstico , Bortezomib/efeitos adversos , Síndrome
3.
Intensive Care Med ; 48(10): 1382-1396, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35960275

RESUMO

In this narrative review, we discuss the relevant issues of therapeutic plasma exchange (TPE) in critically ill patients. For many conditions, the optimal indication, device type, frequency, duration, type of replacement fluid and criteria for stopping TPE are uncertain. TPE is a potentially lifesaving but also invasive procedure with risk of adverse events and complications and requires close monitoring by experienced teams. In the intensive care unit (ICU), the indications for TPE can be divided into (1) absolute, well-established, and evidence-based, for which TPE is recognized as first-line therapy, (2) relative, for which TPE is a recognized second-line treatment (alone or combined) and (3) rescue therapy, where TPE is used with a limited or theoretical evidence base. New indications are emerging and ongoing knowledge gaps, notably regarding the use of TPE during critical illness, support the establishment of a TPE registry dedicated to intensive care medicine.


Assuntos
Unidades de Terapia Intensiva , Troca Plasmática , Estado Terminal/terapia , Humanos , Troca Plasmática/efeitos adversos , Troca Plasmática/métodos , Plasmaferese , Respiração Artificial , Estudos Retrospectivos
6.
Mol Ther Methods Clin Dev ; 13: 303-309, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-30911587

RESUMO

Although the risk of developing lymphoma has decreased in the highly active antiretroviral therapy era, this cancer remains the major cause of mortality in HIV-infected patients. Autologous hematopoietic stem cell transplantation (ASCT) outcome does not differ for HIV-infected versus HIV-uninfected patients. We propose to develop a new treatment for HIV-associated high-risk lymphoma based on autologous transplantation of two genetically modified products: CD4+ T lymphocytes and CD34+ hematopoietic stem cells (HSPCs). The cells will be transduced ex vivo with the Cal-1 lentiviral vector encoding for both a short hairpin RNA (shRNA) against CCR5 (sh5) and the HIV-1 fusion inhibitor C46. The transduced cells will be resistant to HIV infection by two complementary mechanisms: impaired binding of the virus to the cellular CCR5 co-receptor and decreased fusion of the virus as C46 interacts with gp41 and inhibits HIV infection. This phase I/II pilot study, also entitled GENHIV, will involve two French participating centers: Saint Louis Hospital and Necker Hospital in Paris. We plan to enroll five HIV-1-infected patients presenting with high-risk lymphoma and require a treatment with ASCT. The primary objective of this study is to evaluate the safety, feasibility, and success of engraftment of Cal-1 gene-transduced CD4+ T lymphocytes and CD34+ HSPCs.

9.
Am J Trop Med Hyg ; 92(2): 270-3, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25535313

RESUMO

A 30-year-old woman with a history of contact lens wear and exposure to swimming pool water in Thailand presented with a non-responsive, progressive corneal ulcer of the right eye. Confocal microscopy evidenced septate linear branching structures, raising suspicion of fungal keratitis. She was promptly treated with topical antibiotics and both topical and intravenous caspofungin plus voriconazole. Worsening of the clinical picture after 1 month of intensive medical therapy led to a large therapeutic penetrating keratoplasty being performed. Corneal cultures grew a mold-like organism, which was identified by sequencing as Pythium insidiosum, an aquatic oomycete. After 4 years of follow-up, the graft exhibits no infection relapse, but graft transparency has been lost after two rejection episodes. Keratoplasty combined with antifungal treatment may offer a cure to P. insidiosum keratitis, although long-term preservation of corneal transparency is difficult to obtain.


Assuntos
Lentes de Contato/efeitos adversos , Ceratite/etiologia , Pitiose/etiologia , Pythium , Adulto , Lentes de Contato/microbiologia , Córnea/microbiologia , Córnea/patologia , Feminino , França/epidemiologia , Humanos , Ceratite/diagnóstico , Ceratite/epidemiologia , Ceratite/microbiologia , Ceratite/patologia , Pitiose/diagnóstico , Pitiose/epidemiologia , Pitiose/patologia , Natação , Piscinas , Tailândia/epidemiologia , Viagem
10.
Transfusion ; 53(3): 564-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22725259

RESUMO

BACKGROUND: This report describes the specific kinetics of the peripheral blood (PB) CD34+ cell concentration in a selected group of very poor stem cell mobilizer patients treated with granulocyte-colony-stimulating factor (G-CSF) and plerixafor and determines the kinetics' impact on apheresis. STUDY DESIGN AND METHODS: All patients had previously experienced at least two failures of mobilization (without use of plerixafor). The present salvage therapy consisted in the administration of 10 µg/kg/day G-CSF for 5 days added to a dose of plerixafor administered at between 5 a.m. and 6 a.m. on Day 5. The PB CD34+ cell counts were tested every 3 hours thereafter. Apheresis was initiated as soon as the PB CD34+ cell count reached 10 × 10(6) /L. RESULTS: A PB CD34+ cell count higher than 10 × 10(6) /L was observed as soon as 3 hours after plerixafor administration in 10 of the 11 patients who reached this threshold at some point in the monitoring process. Interestingly, all patients presented an early decrease in the PB CD34+ cell count 8 to 12 hours after plerixafor administration (below 10 × 10(6) /L for seven patients). CONCLUSION: Had such patients been tested for PB CD34+ cell mobilization according to conventional criteria (i.e., 11 hr after plerixafor administration), apheresis would not have been performed at the optimal timing. For very poor stem cell mobilizer patients, early monitoring of PB CD34+ cell count may be required for the optimal initiation of apheresis.


Assuntos
Antígenos CD34/metabolismo , Remoção de Componentes Sanguíneos/métodos , Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/administração & dosagem , Adulto , Idoso , Antígenos CD34/sangue , Benzilaminas , Contagem de Células Sanguíneas , Células Sanguíneas/metabolismo , Ciclamos , Esquema de Medicação , Sinergismo Farmacológico , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/farmacologia , Compostos Heterocíclicos/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/terapia , Transplante de Células-Tronco de Sangue Periférico , Fatores de Tempo , Falha de Tratamento
11.
Blood ; 116(8): 1280-90, 2010 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-20484083

RESUMO

GATA-3 and c-Myb are core elements of a transcriptionally active complex essential for human Th2 cell development and maintenance. We report herein mechanistic details concerning the role of these transcription factors in human peripheral blood Th2 cell development. Silencing c-Myb in normal human naive CD4(+) cells under Th2 cell-promoting conditions blocked up-regulation of GATA-3 and interleukin-4, and in effector/memory CD4(+) T cells, decreased expression of GATA-3 and Th2 cytokines. In primary T cells, c-Myb allows GATA-3 to autoactivate its own expression, an event that requires the direct interaction of c-Myb and GATA-3 on their respective binding sites in promoter of GATA-3. Immunoprecipitation revealed that the c-Myb/GATA-3 complex contained Menin and mixed lineage leukemia (MLL). MLL recruitment into the c-Myb-GATA-3-Menin complex was associated with the formation Th2 memory cells. That MLL-driven epigenetic changes were mechanistically important for this transition was suggested by the fact that silencing c-Myb significantly decreased the methylation of histone H3K4 and the acetylation of histone H3K9 at the GATA-3 locus in developing Th2 and CD4(+) effector/memory cells. Therefore, c-Myb, GATA-3, and Menin form a core transcription complex that regulates GATA-3 expression and, with the recruitment of MLL, Th2 cell maturation in primary human peripheral blood T cells.


Assuntos
Fator de Transcrição GATA3/metabolismo , Proteína de Leucina Linfoide-Mieloide/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Células Th2/citologia , Transcrição Gênica , Acetilação , Western Blotting , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Diferenciação Celular , Imunoprecipitação da Cromatina , Citocinas/metabolismo , Metilação de DNA , Fator de Transcrição GATA3/genética , Histona-Lisina N-Metiltransferase , Humanos , Memória Imunológica , Células Jurkat , Luciferases/metabolismo , Proteína de Leucina Linfoide-Mieloide/genética , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myc/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Th1/citologia , Células Th1/imunologia , Células Th1/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Ativação Transcricional
12.
J Allergy Clin Immunol ; 125(2 Suppl 2): S336-44, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20061008

RESUMO

There are many types of stem cells. All share the characteristics of being able to self-renew and to give rise to differentiated progeny. Over the last decades, great excitement has been generated by the prospect of being able to exploit these properties for the repair, improvement, and/or replacement of damaged organs. However, many hurdles, both scientific and ethical, remain in the path of using human embryonic stem cells for tissue-engineering purposes. In this report we review current strategies for isolating, enriching, and, most recently, inducing the development of human pluripotent stem cells. In so doing, we discuss the scientific and ethical issues associated with this endeavor. Finally, progress in the use of stem cells as therapies for type 1 diabetes mellitus, congestive heart failure, and various neurologic and immunohematologic disorders, and as vehicles for the delivery of gene therapy, is briefly discussed.


Assuntos
Células-Tronco Adultas/transplante , Terapia Baseada em Transplante de Células e Tecidos/tendências , Células-Tronco Embrionárias/transplante , Medicina Regenerativa/tendências , Transplante de Células-Tronco , Animais , Diferenciação Celular/genética , Humanos , Medicina Regenerativa/ética , Medicina Regenerativa/métodos , Nicho de Células-Tronco , Engenharia Tecidual , Ativação Transcricional
13.
Ann N Y Acad Sci ; 1153: 20-8, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19236324

RESUMO

Some molecules described in the nervous system are also expressed in cells involved in the control of the immune response, suggesting they have a role as common mechanisms between neuroendocrine and immune systems. In this review, we focus on the expression and role of neuropilins (NPs) and their soluble ligands class 3 semaphorins in thymus physiology, particularly migration of developing thymocytes. We also discuss the concept of multivectorial thymocyte migration, including semaphorins, as a new individual cell migration vector.


Assuntos
Neuropilinas/metabolismo , Semaforinas/metabolismo , Timo/citologia , Timo/metabolismo , Animais , Movimento Celular , Humanos , Sistema Nervoso/metabolismo , Linfócitos T/citologia , Linfócitos T/metabolismo , Timo/patologia
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