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1.
Diagn Interv Imaging ; 99(10): 615-624, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29773346

ABSTRACT

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.


Subject(s)
Device Removal , Vena Cava Filters , Adolescent , Adult , Aged , Aged, 80 and over , Angiography , Female , Foreign-Body Migration/complications , Humans , Male , Middle Aged , Prosthesis Design , Retrospective Studies , Treatment Outcome , Vena Cava, Inferior/diagnostic imaging , Young Adult
2.
Encephale ; 41(4 Suppl 1): S50-5, 2015 Sep.
Article in French | MEDLINE | ID: mdl-26746323

ABSTRACT

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.


Subject(s)
Crisis Intervention/methods , Emergency Medical Services , Emergency Service, Hospital , Humans , Time Factors
3.
Ann Chir Plast Esthet ; 57(4): 350-5, 2012 Aug.
Article in French | MEDLINE | ID: mdl-21945510

ABSTRACT

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.


Subject(s)
Abdominoplasty/methods , Laparoscopy/methods , Muscular Diseases/surgery , Rectus Abdominis , Adult , Female , Humans , Middle Aged
4.
Prog Urol ; 21(12): 859-65, 2011 Nov.
Article in French | MEDLINE | ID: mdl-22035912

ABSTRACT

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.


Subject(s)
Muscle Cells/transplantation , Prostatectomy/adverse effects , Urethra , Urinary Incontinence, Stress/etiology , Urinary Incontinence, Stress/surgery , Aged , Deltoid Muscle , Feasibility Studies , Follow-Up Studies , Humans , Injections, Intralesional , Male , Middle Aged , Prospective Studies , Quality of Life , Risk Assessment , Transplantation, Autologous , Treatment Outcome
5.
Article in English | MEDLINE | ID: mdl-22255395

ABSTRACT

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.


Subject(s)
Anxiety/diagnosis , Dementia/complications , Early Diagnosis , Monitoring, Physiologic/instrumentation , Anxiety/complications , Dementia/physiopathology , Humans , Pilot Projects
6.
Ann Chir Plast Esthet ; 55(5): 354-62, 2010 Oct.
Article in French | MEDLINE | ID: mdl-20869154

ABSTRACT

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.


Subject(s)
Burns/therapy , Radiation Injuries/therapy , Adult , Burns/etiology , Burns/surgery , Combined Modality Therapy , Humans , Male , Mesenchymal Stem Cell Transplantation , Radiation Injuries/complications , Radiation Injuries/surgery
7.
Article in English | MEDLINE | ID: mdl-21502404

ABSTRACT

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.


Subject(s)
Genome/genetics , Nuclear Pore/metabolism , Animals , Gene Expression Regulation , Humans , Mitosis/genetics , Models, Biological , Saccharomyces cerevisiae/cytology , Saccharomyces cerevisiae/metabolism
8.
J Fr Ophtalmol ; 32(5): 350.e1-4, 2009 May.
Article in French | MEDLINE | ID: mdl-19769873

ABSTRACT

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.


Subject(s)
Conjunctival Diseases/parasitology , Dirofilariasis , Eye Infections, Parasitic , Aged, 80 and over , Dirofilariasis/diagnosis , Eye Infections, Parasitic/diagnosis , Female , Humans
9.
Surg Radiol Anat ; 30(4): 285-90, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18330492

ABSTRACT

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.


Subject(s)
Choristoma , Gallbladder/abnormalities , Hepatic Duct, Common/abnormalities , Torsion Abnormality/diagnosis , Aged, 80 and over , Female , Gallbladder/embryology , Gallbladder/surgery , Hepatic Duct, Common/embryology , Humans , Torsion Abnormality/surgery
10.
Regen Med ; 2(5): 785-94, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17907931

ABSTRACT

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.


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Radiation Injuries/surgery , Radiation Injuries/therapy , Adult , Bone Marrow Cells/cytology , Cell Culture Techniques , Cells, Cultured , Dose-Response Relationship, Radiation , Follow-Up Studies , Humans , Male , Phantoms, Imaging , Radiation Injuries/diagnostic imaging , Radiation Injuries/pathology , Radioactive Hazard Release , Radiography , Time Factors , Treatment Outcome
11.
Surg Radiol Anat ; 28(5): 486-93, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17021947

ABSTRACT

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.


Subject(s)
Groin/anatomy & histology , Hernia, Inguinal/surgery , Laparoscopy/methods , Aged , Aged, 80 and over , Female , Humans , Laparoscopy/adverse effects , Male , Middle Aged , Peritoneal Cavity
12.
Kidney Int ; 69(10): 1749-55, 2006 May.
Article in English | MEDLINE | ID: mdl-16625150

ABSTRACT

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.


Subject(s)
Protective Agents/therapeutic use , Reperfusion Injury/prevention & control , Selectins/physiology , Animals , Biphenyl Compounds/chemistry , Biphenyl Compounds/pharmacology , Disease Models, Animal , Fibrosis/pathology , Fibrosis/physiopathology , Immunohistochemistry , Kidney/pathology , Ligands , Male , Mannose/analogs & derivatives , Mannosides/chemistry , Mannosides/pharmacology , Molecular Structure , Nephritis, Interstitial/chemically induced , Nephritis, Interstitial/pathology , Reperfusion Injury/pathology , Selectins/drug effects , Swine , T-Lymphocytes/metabolism
13.
Stem Cells Dev ; 14(2): 204-12, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15910247

ABSTRACT

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.


Subject(s)
Galectin 1/biosynthesis , Mesenchymal Stem Cells/cytology , Proteomics/methods , Amino Acid Sequence , Antibodies, Monoclonal/chemistry , Blotting, Western , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , Cell Differentiation , Cell Membrane/metabolism , Cell Proliferation , Cells, Cultured , Electrophoresis, Gel, Two-Dimensional , Extracellular Matrix/metabolism , Flow Cytometry , Hematopoietic Stem Cells/cytology , Humans , Image Processing, Computer-Assisted , Immunophenotyping , Molecular Sequence Data , Protein Binding , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Time Factors
14.
Rural Remote Health ; 4(3): 286, 2004.
Article in English | MEDLINE | ID: mdl-15885014

ABSTRACT

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.
Article in English | MEDLINE | ID: mdl-12907150

ABSTRACT

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.


Subject(s)
Dystrophin/immunology , Epitopes/immunology , Genetic Therapy/methods , HLA-A Antigens/immunology , Muscular Dystrophy, Duchenne/genetics , Muscular Dystrophy, Duchenne/therapy , Animals , Cells, Cultured , Dystrophin/chemistry , Dystrophin/genetics , Epitopes/chemistry , Epitopes/genetics , Flow Cytometry , HLA-A2 Antigen , Humans , Mice , Mice, Transgenic , Muscular Dystrophy, Duchenne/immunology , T-Lymphocytes, Cytotoxic/immunology
16.
Behav Res Ther ; 41(5): 587-96, 2003 May.
Article in English | MEDLINE | ID: mdl-12711266

ABSTRACT

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.


Subject(s)
Behavior, Addictive/therapy , Cognitive Behavioral Therapy/methods , Gambling/psychology , Psychotherapy, Group/methods , Adult , Analysis of Variance , Female , Follow-Up Studies , Humans , Male , Psychological Tests , Secondary Prevention , Treatment Outcome
17.
J Immunol ; 167(9): 5329-37, 2001 Nov 01.
Article in English | MEDLINE | ID: mdl-11673549

ABSTRACT

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.


Subject(s)
Androstadienes/pharmacology , Anti-Inflammatory Agents/pharmacology , Lung/drug effects , Protein-Tyrosine Kinases , Actins/analysis , Administration, Inhalation , Adult , Androstadienes/administration & dosage , Cell Differentiation , Cells, Cultured , DNA-Binding Proteins/physiology , Fibroblasts/drug effects , Fibroblasts/physiology , Fluticasone , Humans , Interleukin-13/pharmacology , Interleukin-4/pharmacology , Lung/cytology , Microscopy, Confocal , NF-kappa B/metabolism , Proteins/physiology , Reverse Transcriptase Polymerase Chain Reaction , STAT3 Transcription Factor , TYK2 Kinase , Trans-Activators/physiology
18.
Arterioscler Thromb Vasc Biol ; 21(8): 1353-8, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11498465

ABSTRACT

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.


Subject(s)
Apolipoproteins A/chemistry , Hypercholesterolemia/metabolism , Adolescent , Adult , Aged , Apolipoproteins A/blood , Apolipoproteins A/urine , Female , Humans , Lipids/blood , Lipoprotein(a)/blood , Male , Middle Aged , Protein Isoforms
19.
J Nerv Ment Dis ; 189(11): 774-80, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11758661

ABSTRACT

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.


Subject(s)
Cognitive Behavioral Therapy/methods , Gambling/psychology , Adult , Female , Follow-Up Studies , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Treatment Outcome
20.
Oncogene ; 19(51): 5898-905, 2000 Nov 30.
Article in English | MEDLINE | ID: mdl-11127821

ABSTRACT

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.


Subject(s)
Interleukin-13/pharmacology , Interleukin-4/pharmacology , Lung Neoplasms/metabolism , Lung/metabolism , Signal Transduction/drug effects , DNA-Binding Proteins/metabolism , Dose-Response Relationship, Drug , Enzyme Activation , Fibroblasts/drug effects , Fibroblasts/enzymology , Fibroblasts/metabolism , Humans , Insulin Receptor Substrate Proteins , Intracellular Signaling Peptides and Proteins , Janus Kinase 1 , Lung/cytology , Lung/drug effects , Lung Neoplasms/enzymology , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/physiology , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3 , Mitogen-Activated Protein Kinases/metabolism , Phosphoproteins/metabolism , Phosphorylation/drug effects , Protein-Tyrosine Kinases/metabolism , Receptors, Interleukin-4/metabolism , STAT1 Transcription Factor , STAT3 Transcription Factor , STAT6 Transcription Factor , Signal Transduction/physiology , Trans-Activators/metabolism
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