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1.
Diagn Interv Imaging ; 99(10): 615-624, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29773346

RESUMO

PURPOSE: To compare changes in inferior vena cava (IVC) filter positional parameters from insertion to removal and examine how they affect retrievability amongst various filter types. MATERIALS AND METHODS: A total of 447 patients (260 men, 187 women) with a mean age of 55 years (range: 13-91 years) who underwent IVC filter retrieval between 2007-2014 were retrospectively included. Post-insertion and pre-retrieval angiographic studies were assessed for filter tilt, migration, strut wall penetration and retrieval outcomes. ANCOVA and multiple logistic regression models were used to analyze factors affecting retrieval success. Pairwise comparisons between filter types were performed. RESULTS: Of 488 IVC filter retrieval attempts, 94.1% were ultimately successful. The ALN filter had the highest mean absolute value of tilt (5.6 degrees), the Optease filter demonstrated the largest mean migration (-8.0mm) and the Bard G2 filter showed highest mean penetration (5.2mm). Dwell time of 0-90 days (OR, 11.1; P=0.01) or 90-180 days (OR, 2.6; P=0.02), net tilt of 10-15 degrees (OR 8.9; P=0.05), caudal migration of -10 to 0mm (OR, 3.46; P=0.03) and penetration less than 3mm (OR, 2.6; P=0.01) were positive predictors of successful retrievability. Higher odds of successful retrieval were obtained for the Bard G2X, Bard G2 and Cook Celect when compared to the ALN and Cordis Optease filters. CONCLUSION: Shorter dwell time, lower mean tilt, caudal migration and less caval wall penetration are positive predictors of successful IVC filter retrieval.


Assuntos
Remoção de Dispositivo , Filtros de Veia Cava , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia , Feminino , Migração de Corpo Estranho/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Estudos Retrospectivos , Resultado do Tratamento , Veia Cava Inferior/diagnóstico por imagem , Adulto Jovem
2.
Encephale ; 41(4 Suppl 1): S50-5, 2015 Sep.
Artigo em Francês | MEDLINE | ID: mdl-26746323

RESUMO

OBJECTIVE: Group debriefing has been a topic of controversy regarding its temporal dimension. What is the opportune time for using this communication device and when is it the most effective? In practice, group debriefing is generally used after the fact, in post-event interventions. What is the rationale for delaying the debriefing process? Debriefing follows a logical progression that goes from evocation of the event to the expression of a possible future. How should one view this progression in relation to the subject's logical temporality? Finally, are the temporalities of the subjects and the group compatible? The objective of this paper is to show that one of the particularities of group debriefing is that it associates group temporality and subjective logical time. METHODOLOGY: This study describes the temporal modalities of group debriefing practiced at the Emergency Medical-Psychological Unit of the Ille-et-Vilaine Department of France, based on the analysis of a clinical case. The debriefing situation presented here took place in a firm following a suicide. Four female employees of the firm saw the body of a person committing suicide as it fell from the higher floors of the building. The psychoanalytic research on subjective time, used as a basis for this study, points out two dimensions of time, prograde and retrograde. Retrograde time produces a feedback effect via which the subject reorganizes his/her past. Psychoanalysis also describes a logical time specific to each subject, which can be broken down into three time frames: seeing, understanding, and concluding. In group debriefing, the time course is group-specific. RESULTS: We show that the subjects' temporality is interconnected with the temporal progression of the group during debriefing. We present some elements showing how subjective and group positioning evolved in relation to the shared temporal unfolding of the debriefing. The debriefing consisted of three time frames. The first involved evoking the tragic experience of the event; it brought out the common points in the women's experience of the event, and a solution of "withdrawal" as a protection mechanism. Individual experiences, such as the desire to avoid or see the scene, or the ability or inability to call for help, were also present. The second time frame pertained to the symptomatology and subsequent experience of the event; here, we observed evocation of similar symptoms among some of the participants but also after the event, depending on individual subjectivity. The relationship to the event was also addressed in terms of the ability or inability of each individual to cope with the event and overcome it. The third time frame involved projection into the future; a sense of relief became manifest as the debriefing progressed. This third time frame permitted evocation of a possible way of "breaking away" from the event, linked to each person's history and connected in particular to the relationship with death evoked during the second time frame. The debriefing also helped in acknowledging the pain brought about by the traumatic event, a beneficial factor in psychic processing. CONCLUSION: Group debriefing articulates subjective time and group time. In practice, debriefing follows chronological time, at the same time as it mobilizes logical time. It brings to bear a double temporality that must be taken into account during both the implementation and unfolding phases of the debriefing process, but also in the objectives set for this device. The clinician-debriefer must consider this double temporality in order to direct the debriefing in a way suited to the clinical implications that justify its use, and must do so with tact and moderation, without imposition on the subjects'individual temporalities and defenses.


Assuntos
Intervenção em Crise/métodos , Serviços Médicos de Emergência , Serviço Hospitalar de Emergência , Humanos , Fatores de Tempo
3.
Ann Chir Plast Esthet ; 57(4): 350-5, 2012 Aug.
Artigo em Francês | MEDLINE | ID: mdl-21945510

RESUMO

UNLABELLED: In 10 cases of abdominoplasty where an important rectus diastasis had to be corrected, we completed the plication of the rectus sheath included in a classical abdominoplasty with the laparoscopic positioning of an intraperitoneal prosthesis. PURPOSE: To assess the middle-term results of this technique and present its advantages and drawbacks. PATIENTS AND METHOD: Fifteen patients have been operated from 2007 to 2011 by two surgeon teams. Ten of them have accepted to be included in our survey. RESULTS: All the patients said they were satisfied with their surgery. Four of them reported mild pain during the first postoperative weeks, and two of them mentioned very moderate pain at the time of the survey. The surgeons were not satisfied with the results obtained in two cases. Only one of these two patients accepted revision abdominoplasty with a good result. CONCLUSION: Laparoscopic positioning of an intraperitoneal prosthesis, coupled with a classical plication of the rectus sheath, gives excellent results in difficult cases of rectus diastasis.


Assuntos
Abdominoplastia/métodos , Laparoscopia/métodos , Doenças Musculares/cirurgia , Reto do Abdome , Adulto , Feminino , Humanos , Pessoa de Meia-Idade
4.
Prog Urol ; 21(12): 859-65, 2011 Nov.
Artigo em Francês | MEDLINE | ID: mdl-22035912

RESUMO

PURPOSE: Cell therapy for urinary incontinence management has been experienced in animals with encouraging results, but studies in human beings are lacking. Our primary objective was to assess the safety of intrasphincteric injections of autologous muscular cells in patients with postprostatectomy incontinence (PPI). Secondary objectives focused on complications efficacy. METHODS: We conducted an open, prospective study in a single center on 12 patients presenting PPI. Patients underwent intrasphincteric injections of autologous muscular cells isolated from a biopsy of deltoid muscle. The primary endpoint was the Q(max) variation at the three month visit in order to assess potential bladder outlet obstruction. Secondary endpoints assessed side effects and efficacy parameters based on symptoms, quality of life score, voiding diary, pad-test, and urethral pressure profile at one, two, three, six and 12 months after injection. RESULTS: No immediate complication occurred and no significant variation was noted on Q(max). The only side effects possibly product-related were three cases of urinary tract infection treated by antibiotics. An acceptable safety and tolerability of the procedure whatever the injected dose of muscular cells was demonstrated. Results on efficacy after one year were heterogeneous, with 4/12 patients describing reduced urine leakage episodes, 1/12 patient presenting increased maximal closure pressure, and 8/12 patients showing improvement on pad-test. CONCLUSIONS: Cell therapy consisting of intrasphincteric injections of autologous muscular cells in patients with PPI was a feasible and safe procedure. The results point out that some subjects may positively respond to this procedure, but clinical efficacy remains to be confirmed.


Assuntos
Células Musculares/transplante , Prostatectomia/efeitos adversos , Uretra , Incontinência Urinária por Estresse/etiologia , Incontinência Urinária por Estresse/cirurgia , Idoso , Músculo Deltoide , Estudos de Viabilidade , Seguimentos , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Medição de Risco , Transplante Autólogo , Resultado do Tratamento
5.
Artigo em Inglês | MEDLINE | ID: mdl-22255395

RESUMO

The negative behavioral and psychological symptoms (NBPS) seen in patients with cognitive impairment (CI), such as anxiety, agitation and aggression have been reported to be the most problematic for healthcare providers. The consequences of delayed detection of NBPS can be devastating for both patients and caregivers; therefore early detection of symptoms that may lead into NBPS is essential. A proprietary device called portable autonomous multisensory intervention device (PAMID) has been developed to not only wirelessly monitor physiological conditions as a means for early detection of NBPS, but also automatically provide a real-time multisensory intervention to reduce NBPS in patients with CI if thresholds of physiological parameters reflecting the symptoms are detected. This paper outlines the enhancement of PAMID and test results from a pilot study. This device to be developed will have significant applications in the emerging Tele-healthcare systems.


Assuntos
Ansiedade/diagnóstico , Demência/complicações , Diagnóstico Precoce , Monitorização Fisiológica/instrumentação , Ansiedade/complicações , Demência/fisiopatologia , Humanos , Projetos Piloto
6.
Ann Chir Plast Esthet ; 55(5): 354-62, 2010 Oct.
Artigo em Francês | MEDLINE | ID: mdl-20869154

RESUMO

Radiation burn is a determinist effect of localized irradiation. The lesion is in good correlation with absorbed dose. Radiation burn is different from thermal burn. The evolution is spatiotemporal unpredictable with successive inflammatory waves and recurrence of necrosis. The conventional surgical treatment is rarely efficient because each surgical operative act seems to stimulate the inflammatory waves and fibro-necrosis process. The lesion can escape to this conventional surgical treatment. The new therapeutic approach combines surgery and cellular therapy with local administration of autologous mesenchymal stem cells. From 5 years, cell therapy have been an adjuvant treatment of surgery. This association is a therapeutic innovation, it's now the recommendation for conservative surgery of this very serious radiation burn.


Assuntos
Queimaduras/terapia , Lesões por Radiação/terapia , Adulto , Queimaduras/etiologia , Queimaduras/cirurgia , Terapia Combinada , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais , Lesões por Radiação/complicações , Lesões por Radiação/cirurgia
7.
Artigo em Inglês | MEDLINE | ID: mdl-21502404

RESUMO

Eukaryotic cell function depends on the physical separation of nucleoplasmic and cytoplasmic components by the nuclear envelope (NE). Molecular communication between the two compartments involves active, signal-mediated trafficking, a function that is exclusively performed by nuclear pore complexes (NPCs). The individual NPC components and the mechanisms that are involved in nuclear trafficking are well documented and have become textbook knowledge. However, in addition to their roles as nuclear gatekeepers, NPC components-nucleoporins-have been shown to have critical roles in chromatin organization and gene regulation. These findings have sparked new enthusiasm to study the roles of this multiprotein complex in nuclear organization and explore novel functions that in some cases appear to go beyond a role in transport. Here, we discuss our present view of NPC biogenesis, which is tightly linked to proper cell cycle progression and cell differentiation. In addition, we summarize new data suggesting that NPCs represent dynamic hubs for the integration of gene regulation and nuclear transport processes.


Assuntos
Genoma/genética , Poro Nuclear/metabolismo , Animais , Regulação da Expressão Gênica , Humanos , Mitose/genética , Modelos Biológicos , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/metabolismo
8.
J Fr Ophtalmol ; 32(5): 350.e1-4, 2009 May.
Artigo em Francês | MEDLINE | ID: mdl-19769873

RESUMO

INTRODUCTION: Dirofilariasis is a disease rarely seen in humans, occurring commonly in noncarnivorous mammals. The microfilariae are transmitted by a mosquito vector. Ocular dirofilariasis is rarely described in the ophthalmic literature. CASE REPORT: An 81-year-old woman living in the north of France had a history of sudden pain and swelling of the left orbit. On slit lamp examination, a white worm was seen under the superior bulbar conjunctiva. Excision of the subconjunctival worm was adequate treatment and was important for parasite identification. DISCUSSION: Dirofilariasis is broad-based and is more common in Italy. Cases in France are found in the south. Ocular symptoms are frequently subconjunctival, but many cases of orbital involvement are found. Treatment is only surgical; systemic medication is not necessary. CONCLUSION: Ocular dirofilariasis is exceptional. Case reports in ophthalmic literature are rare. This parasite infection is probably underdiagnosed.


Assuntos
Doenças da Túnica Conjuntiva/parasitologia , Dirofilariose , Infecções Oculares Parasitárias , Idoso de 80 Anos ou mais , Dirofilariose/diagnóstico , Infecções Oculares Parasitárias/diagnóstico , Feminino , Humanos
9.
Surg Radiol Anat ; 30(4): 285-90, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18330492

RESUMO

The aim of this review of the literature was to present and discuss the anatomical and embryological basis of congenital abnormalities of the gallbladder, based on a case of volvulus. In the rare cases of ectopic gallbladder, diagnosis of a biliary disease could be difficult. In such cases surgery can also be dangerous, especially when it is associated with abnormalities of the intra-hepatic biliary and vascular tree. This study, based on the embryology of the extra hepatic bile duct, focused on the most frequent gallbladder abnormalities to keep them in mind.


Assuntos
Coristoma , Vesícula Biliar/anormalidades , Ducto Hepático Comum/anormalidades , Anormalidade Torcional/diagnóstico , Idoso de 80 Anos ou mais , Feminino , Vesícula Biliar/embriologia , Vesícula Biliar/cirurgia , Ducto Hepático Comum/embriologia , Humanos , Anormalidade Torcional/cirurgia
10.
Regen Med ; 2(5): 785-94, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17907931

RESUMO

The therapeutic management of severe radiation burns remains a challenging issue. Conventional surgical treatment (excision and skin autograft or rotation flap) often fails to prevent unpredictable and uncontrolled extension of the radiation necrotic process. We report here an innovative therapeutic strategy applied to the victim of a radiation accident (December 15, 2005) with an iridium gammagraphy radioactive source (192Ir, 3.3 TBq). The approach combined numerical dosimetry-guided surgery with cellular therapy using mesenchymal stem cells. A very severe buttock radiation burn (2000 Gy at the center of the skin surface lesion) of a 27-year-old Chilean victim was widely excised (10 cm in diameter) using a physical and anatomical dose reconstruction in order to better define the limit of the surgical excision in apparently healthy tissues. A secondary extension of the radiation necrosis led to a new excision of fibronecrotic tissues associated with a local cellular therapy using autologous expanded mesenchymal stem cells as a source of trophic factors to promote tissue regeneration. Bone marrow-derived mesenchymal stem cells were expanded according to a clinical-grade technique using closed culture devices and serum-free medium enriched in human platelet lysate. The clinical evolution (radiation pain and healing progression) was favorable and no recurrence of radiation inflammatory waves was observed during the 11 month patient's follow-up. This novel multidisciplinary therapeutic approach combining physical techniques, surgical procedures and cellular therapy with adult stem cells may be of clinical relevance for improving the medical management of severe localized irradiations. It may open new prospects in the field of radiotherapy complications.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Lesões por Radiação/cirurgia , Lesões por Radiação/terapia , Adulto , Células da Medula Óssea/citologia , Técnicas de Cultura de Células , Células Cultivadas , Relação Dose-Resposta à Radiação , Seguimentos , Humanos , Masculino , Imagens de Fantasmas , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/patologia , Liberação Nociva de Radioativos , Radiografia , Fatores de Tempo , Resultado do Tratamento
11.
Surg Radiol Anat ; 28(5): 486-93, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17021947

RESUMO

PURPOSE: The totally extraperitoneal laparoscopic approach for the treatment of inguinal hernia is a well-recognized technique with proven efficacy, low failure rate, and reduced post-operative pain. This laparoscopic technique is reputed to be a more difficult procedure to learn and practice than a laparoscopic trans-abdomino-pre-peritoneal procedure: we hope this is because many surgeons don't well know extra-peritoneal anatomy of groin. So we proposed a "step by step" anatomical analysis, with pitfalls to avoid, of a totally extraperitoneal laparoscopic approach for treatment of inguinal hernia. METHODS: Our experience with totally extraperitoneal laparoscopic inguinal hernia repair with regard to the morphology of the inguinal-femoral region concerns 23 cadaver dissection and more than 400 surgical procedures, now permits clarification of a surgical technique that has hitherto not been well known. CONCLUSION: Photographic representations of surgical views are displayed, and detailed descriptions applicable to anatomical structures are presented.


Assuntos
Virilha/anatomia & histologia , Hérnia Inguinal/cirurgia , Laparoscopia/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Cavidade Peritoneal
12.
Kidney Int ; 69(10): 1749-55, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16625150

RESUMO

Experiments in rodents have demonstrated an important role for selectins in kidney ischemia-reperfusion injury (IRI). However, the relevance of this in larger mammals, as well as the impact on long-term structure and function is unknown. We tested the hypothesis that small molecule selectin ligand inhibition attenuates IRI, cellular inflammation, and long-term effects on renal interstitial fibrosis. We used a porcine model of kidney IRI and used Texas Biotechnology Corporation (TBC)-1269, a selectin ligand inhibitor. Renal function, tissue inflammation, and tubulointerstitial fibrosis development were evaluated up to 16 weeks. Both warm and cold ischemia models were studied for relevance to native and transplant kidney injury. Pigs treated with TBC-1269 during 45 min of warm ischemia (WI) showed significantly increased glomerular filtration rate compared to control animals. In pigs with severe IRI (WI for 60 min), TBC-1269 treatment during IRI significantly increased renal recovery. Cellular inflammation was strongly reduced, particularly influx of CD4 cells. Quantitative measurement of fibrosis by picrosirius red staining showed strong reduction in TBC-1269-treated groups. TBC-1269 also reduced cold IRI, inflammation, and fibrosis in kidneys preserved for 24 h at 4 degrees C and autotransplanted. The selectin ligand inhibitor TBC-1269 provides a novel and effective approach to attenuate IRI in both warm and cold ischemia in large mammals, in both short and long terms. Selectin ligand inhibition is an attractive strategy for evaluation in human kidney IRI.


Assuntos
Substâncias Protetoras/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Selectinas/fisiologia , Animais , Compostos de Bifenilo/química , Compostos de Bifenilo/farmacologia , Modelos Animais de Doenças , Fibrose/patologia , Fibrose/fisiopatologia , Imuno-Histoquímica , Rim/patologia , Ligantes , Masculino , Manose/análogos & derivados , Manosídeos/química , Manosídeos/farmacologia , Estrutura Molecular , Nefrite Intersticial/induzido quimicamente , Nefrite Intersticial/patologia , Traumatismo por Reperfusão/patologia , Selectinas/efeitos dos fármacos , Suínos , Linfócitos T/metabolismo
13.
Stem Cells Dev ; 14(2): 204-12, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15910247

RESUMO

Bone marrow-derived mesenchymal stem cells (MSCs) are known to interact with hematopoietic stem cells (HSCs) and immune cells, and are of potential interest to be used as therapeutic agents for enhancing allogenic hematopoietic engraftment and preventing graft-versus-host disease (GVHD). Galectin 1 (Gal1) belongs to a family of structurally related molecules expressed in many vertebrate tissues that exert their functions both by binding to glycoconjugates, and by interaction with protein partners. In this work using a proteomic approach, we looked for the presence and the localization of Gal1 in short- and long-term culture of human (h) hMSC. We first determined, that Gal1 is one of the major proteins expressed in hMSC. We futher demonstrated that its expression is maintained when hMSC are expanded through a subculturing process up to five passages. Moreover, Gal1 is secreted and found at the cell surface of MSC, participating in extra cellular matrix (ECM)-cell interactions. Given the immunomodulatory properties of Gal1, its potential involvement in immunological functions of hMSC could be suggested.


Assuntos
Galectina 1/biossíntese , Células-Tronco Mesenquimais/citologia , Proteômica/métodos , Sequência de Aminoácidos , Anticorpos Monoclonais/química , Western Blotting , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Diferenciação Celular , Membrana Celular/metabolismo , Proliferação de Células , Células Cultivadas , Eletroforese em Gel Bidimensional , Matriz Extracelular/metabolismo , Citometria de Fluxo , Células-Tronco Hematopoéticas/citologia , Humanos , Processamento de Imagem Assistida por Computador , Imunofenotipagem , Dados de Sequência Molecular , Ligação Proteica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Fatores de Tempo
14.
Rural Remote Health ; 4(3): 286, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15885014

RESUMO

INTRODUCTION: Adults frequently rely on self-treatment modalities to relieve pain that exceeds everyday kinds of pain, such as minor headaches and toothaches. Examples of self-treatment modalities include doctor-prescribed analgesics, non-prescribed over-the counter medications, herbal substances and treatments, and non-drug treatments such as heat, cold and exercise. Self-treatment is often associated with adverse affects related to the improper use of self-treatment substances and the adverse interactions they may produce when combined with other prescribed or non-prescription treatments for pain control. Many adults also use a variety of self-treatment modalities without informing their health care providers. OBJECTIVES: To explore the occurrence of pain and identify pain self-treatment modalities used by members (n = 105) of rural communities from two eastern Canadian provinces. Results of this study were compared with a rural American cohort study in order to explore similarities/differences in patterns of self-treatment of pain between the two countries. METHODS: This descriptive-exploratory study was conducted using a survey method. The design followed that used in a US study by Vallerand, Fouladbakhsh and Templin. Investigators used self-report questionnaires to identify pain self-treatment modalities, pain intensity ratings, pain interference, and the percentage of pain relief in a convenience sample of 105 participants recruited from two Canadian rural communities. Differences in mean scores between Canadian and US data were determined through t-tests. Difference between Canadian and US pain self-treatment modalities were determined using chi2 tests for significance. RESULTS: Canadians reported choosing significantly more non-pharmacological self-treatment modalities of pain control such as heat, cold, exercise/stretching, and massage than did their US counterparts (chi2 = 7.6, p = .006). US participants reported significantly higher percentages of pharmacologic modalities than Canadian participants, ie prescription medications (chi2 = 4.8, p = .03), and over-the counter medications (chi2 = 8.14, p = .004). There was no significant difference between the two countries in the number of herbal supplements taken for pain relief (chi2 = 2.47, p = .12). Canadian participants reported having significantly less pain relief from their current self-treatment regimen than US participants, (t = 13.77, p = .00). In addition, 33% of Canadian participants and 20% of US participants had not informed their primary care practitioner of their self-treatment choices. CONCLUSIONS: This study demonstrates that pain is a common experience for many North American individuals living in rural communities. Comparison of results between Canadian and US cohort studies indicate that rural Canadians may benefit from increasing their knowledge about self-treatment options of pain control. Findings showed that rural Canadians choose more non-pharmacologic self-treatment modalities and have less pain relief than rural US participants by their self-treatment choices. In addition, a significant number of Canadian and US participants had not informed their primary care provider of their self-treatment practices. Community healthcare agencies may need to improve the dissemination of information on how to combine both pharmacologic and non-pharmacologic modalities into self-treatment regimens in order to facilitate more effective pain control for some rural communities. Further study is indicated to examine how the differences found in self-treatment practices between Canadian and US cohort studies relate to the differences between Canadian and US culture and healthcare payment systems.

15.
Mol Ther ; 8(2): 274-83, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12907150

RESUMO

Dystrophin-based gene therapy treatments aimed at correcting the Duchenne muscular dystrophy phenotype require stable expression of normal dystrophin (DYST) protein in myocytes without immune responses, which would compromise long-term expression. To predict cytotoxic T-cell-mediated responses elicited by transgenes, we used here H-2-negative HLA-A*0201 transgenic mice and identified human DYST epitopes, which elicit HLA-A*0201-restricted cytotoxic T cell activities. Among a series of eight peptides predicted from the human DYST sequence, not shared with the endogenous mouse DYST sequence, four of them were able to bind to HLA-A*0201 molecules and to induce cytotoxic T lymphocyte (CTL) responses. After human DYST DNA transfer in muscle of HLA-A*0201 mice, only the human DYST1281 epitope, located in the spectrin-like repeat 9 domain, induced strong CD8(+) CTL responses. Using the corresponding human DYST1281 peptide/HLA-A*0201 tetramer, we detected human DYST1281-specific CD8(+) T cells in peripheral lymphoid organs and blood of HLA-A*0201 mice injected with human DYST DNA. Our results demonstrate that muscle injection with human DYST DNA systematically triggers CTL responses against this HLA-A*0201-restricted human DYST1281 peptide, which is present in long human DYST isoforms. Identification of such immunodominant human DYST epitopes and use of peptide/HLA tetramers will allow the immunomonitoring of CTL responses in HLA-phenotyped Duchenne muscular dystrophy patients undergoing gene therapy. Finally, the knowledge of HLA-A*0201-restricted human DYST peptides will be of importance to test, in mouse models, new immunomodulatory interventions allowing long-term engraftment of human dystrophin.


Assuntos
Distrofina/imunologia , Epitopos/imunologia , Terapia Genética/métodos , Antígenos HLA-A/imunologia , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia , Animais , Células Cultivadas , Distrofina/química , Distrofina/genética , Epitopos/química , Epitopos/genética , Citometria de Fluxo , Antígeno HLA-A2 , Humanos , Camundongos , Camundongos Transgênicos , Distrofia Muscular de Duchenne/imunologia , Linfócitos T Citotóxicos/imunologia
16.
Behav Res Ther ; 41(5): 587-96, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12711266

RESUMO

This study evaluated the efficacy of a group cognitive treatment for pathological gambling. Gamblers, meeting DSM-IV criteria for pathological gambling, were randomly assigned to treatment (N=34) or wait-list control (N=24) conditions. Cognitive correction techniques were used first to target gamblers' erroneous perceptions about randomness, and then to address issues of relapse prevention. The dependent measures used were the DSM-IV criteria for pathological gambling, perceived self-efficacy, gamblers' perception of control, desire to gamble, and frequency of gambling. Post-treatment results indicated that 88% of the treated gamblers no longer met the DSM-IV criteria for pathological gambling compared to only 20% in the control group. Similar changes were observed on all outcome measures. Analysis of data from 6-, 12- and 24-month follow-ups revealed maintenance of therapeutic gains. Recommendations for group interventions are discussed, focusing on the cognitive correction of erroneous perceptions toward the notion of randomness.


Assuntos
Comportamento Aditivo/terapia , Terapia Cognitivo-Comportamental/métodos , Jogo de Azar/psicologia , Psicoterapia de Grupo/métodos , Adulto , Análise de Variância , Feminino , Seguimentos , Humanos , Masculino , Testes Psicológicos , Prevenção Secundária , Resultado do Tratamento
17.
J Immunol ; 167(9): 5329-37, 2001 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-11673549

RESUMO

Asthma is characterized by an irreversible subepithelial fibrosis with the appearance of myofibroblasts, which can be now considered important early participants in inflammatory responses as well as potential targets for anti-inflammatory drugs. In this study, we show that fluticasone propionate (FP), a powerful inhaled corticosteroid (ICS), displays novel anti-inflammatory effects on human lung fibroblasts during their myofibroblastic differentiation. Indeed, FP inhibits in lung myofibroblasts, at a very early stage of differentiation, the activation of Janus kinase/STAT pathways induced by IL-13 (tyrosine kinase 2, STAT1, STAT3, STAT6, mitogen-activated protein kinase). Contrarily, in mildly or fully differentiated myofibroblastic cultures, FP still displays a potential anti-inflammatory activity even if it only inhibits tyrosine kinase 2 phosphorylation. Moreover, FP inhibits constitutive and TGF-beta-induced expression of alpha-smooth muscle actin, the main marker of myofibroblastic differentiation, both in very early and in mild differentiated myofibroblasts. Finally, FP displays an additional powerful anti-inflammatory effect, decreasing nuclear translocation of NF-kappaB independent of the degree of myofibroblastic differentiation. These data 1) suggest that myofibroblasts are priority targets for ICS, which is able to revert them to a normal phenotype even if they appear to be already engaged in their differentiation, and 2) may help to explain why asthma is improved by an early ICS treatment, whereas advanced asthma is more resistant to these drugs.


Assuntos
Androstadienos/farmacologia , Anti-Inflamatórios/farmacologia , Pulmão/efeitos dos fármacos , Proteínas Tirosina Quinases , Actinas/análise , Administração por Inalação , Adulto , Androstadienos/administração & dosagem , Diferenciação Celular , Células Cultivadas , Proteínas de Ligação a DNA/fisiologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Fluticasona , Humanos , Interleucina-13/farmacologia , Interleucina-4/farmacologia , Pulmão/citologia , Microscopia Confocal , NF-kappa B/metabolismo , Proteínas/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição STAT3 , TYK2 Quinase , Transativadores/fisiologia
18.
Arterioscler Thromb Vasc Biol ; 21(8): 1353-8, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11498465

RESUMO

Hypercholesterolemia is frequently associated with elevated Lp(a) levels, an independent risk factor for coronary, cerebrovascular, and peripheral vascular disease. A portion of apolipoprotein(a) [apo(a)] circulates as a series of fragments derived from the N-terminal region of apo(a). The relationship of elevated lipoprotein(a) [Lp(a)] levels to those of circulating apo(a) fragments in polygenic hypercholesterolemia is indeterminate. Therefore, plasma Lp(a) and plasma and urinary apo(a) fragment levels were measured by ELISA in 82 patients with polygenic type IIa hypercholesterolemia (low density lipoprotein cholesterol >/=4.13 mmol/L and triglycerides <2.24 mmol/L) and in 90 normolipidemic subjects. Lp(a) levels were significantly elevated in patients compared with control subjects (0.35+/-0.4 and 0.24+/-0.31 mg/mL, respectively; median 0.13 and 0.11 mg/mL, respectively; P=0.039), although apo(a) isoform distribution did not differ. Patients displayed significantly higher plasma and urinary apo(a) fragment levels than did control subjects (respective values were as follows: 4.97+/-5.51 and 2.15+/-2.57 [median 2.85 and 1.17] microg/mL in plasma, P<0.0001; 75+/-86 and 40+/-57 [median 38 and 17] ng/mg urinary creatinine in urine, P<0.0001). The ratio of plasma apo(a) fragments to Lp(a) levels was also significantly higher in patients than in control subjects (1.93+/-1.5% and 1.75+/-2.36%, respectively; P<0.0001). We conclude that increased plasma Lp(a) levels in polygenic hypercholesterolemia are associated with elevated circulating levels of apo(a) fragments but that this increase is not due to decreased renal clearance of apo(a) fragments. Furthermore, we identified a new pattern of apo(a) fragmentation characterized by the predominance of a fragment band whose size was related to that of the parent apo(a) isoform and that was superimposed on the series of fragments described previously by Mooser et al (J Clin Invest. 1996; 98:2414-2424). This new pattern was associated with small apo(a) isoforms and did not discriminate between hypercholesterolemic and normal subjects. However, this new apo(a) fragment pattern may constitute a novel marker for cardiovascular risk.


Assuntos
Apolipoproteínas A/química , Hipercolesterolemia/metabolismo , Adolescente , Adulto , Idoso , Apolipoproteínas A/sangue , Apolipoproteínas A/urina , Feminino , Humanos , Lipídeos/sangue , Lipoproteína(a)/sangue , Masculino , Pessoa de Meia-Idade , Isoformas de Proteínas
19.
J Nerv Ment Dis ; 189(11): 774-80, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11758661

RESUMO

This study evaluated the efficacy of a cognitive treatment package for pathological gambling. Sixty-six gamblers, meeting DSM-IV criteria for pathological gambling, were randomly assigned to treatment or wait-list control conditions. Cognitive correction techniques were used first to target gamblers' erroneous perceptions about randomness and then to address issues of relapse prevention. The dependent measures used were the South Oaks Gambling Screen, the number of DSM-IV criteria for pathological gambling met by participants, as well as gamblers' perception of control, frequency of gambling, perceived self-efficacy, and desire to gamble. Posttest results indicated highly significant changes in the treatment group on all outcome measures, and analysis of data from 6- and 12-month follow-ups revealed maintenance of therapeutic gains. Recommendations for clinical interventions are discussed, focusing on the cognitive correction of erroneous perceptions toward the notion of randomness.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Jogo de Azar/psicologia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Resultado do Tratamento
20.
Oncogene ; 19(51): 5898-905, 2000 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-11127821

RESUMO

IL-4 and IL-13 act on human lung fibroblasts through specific receptors differing in their composition. Indeed, the gammac chain is constitutively expressed in tumor lung myofibroblast but not in normal cells. Here, we have analysed the signal transduction induced by IL-4 and IL-13 in both cell types, in order to better understand the molecular mechanisms underlying tumor stromal development. The IL-4Ralpha chain is constitutively phosphorylated and pre-associated with the JAK1 protein in both cell types. In normal cells, we detected the activation of the classic IRS-2 or JAK1/STAT6 pathways, the phosphorylation of JAK2, while Tyk2 was constitutively phosphorylated and not modified by both cytokines. In addition to these pathways, in lung tumor myofibroblasts, IL-4 and IL-13 induced the phosphorylation of JAK3 and increased the phosphorylation of Tyk2. Interestingly, in both cell types IL-4 and IL-13 triggered an unusual pattern of STAT1 and STAT3 activation. These events probably correspond to a tissue-specific signaling important for the immunoregulatory functions of airways fibroblasts. Indeed, the inflammatory-like pattern of STATs signaling triggered by IL-4 and IL-13 in these cells may favor the homing of inflammatory and/or metastatic cells. In lung myofibroblasts, these properties could be modified through the different pattern of JAK activation.


Assuntos
Interleucina-13/farmacologia , Interleucina-4/farmacologia , Neoplasias Pulmonares/metabolismo , Pulmão/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Relação Dose-Resposta a Droga , Ativação Enzimática , Fibroblastos/efeitos dos fármacos , Fibroblastos/enzimologia , Fibroblastos/metabolismo , Humanos , Proteínas Substratos do Receptor de Insulina , Peptídeos e Proteínas de Sinalização Intracelular , Janus Quinase 1 , Pulmão/citologia , Pulmão/efeitos dos fármacos , Neoplasias Pulmonares/enzimologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosfoproteínas/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Tirosina Quinases/metabolismo , Receptores de Interleucina-4/metabolismo , Fator de Transcrição STAT1 , Fator de Transcrição STAT3 , Fator de Transcrição STAT6 , Transdução de Sinais/fisiologia , Transativadores/metabolismo
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