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1.
Clin Oncol (R Coll Radiol) ; 35(6): e352-e361, 2023 06.
Article de Anglais | MEDLINE | ID: mdl-37031075

RÉSUMÉ

AIMS: Clinical equipoise exists regarding early-stage lung cancer treatment among patients as trials comparing stereotactic body radiation therapy (SBRT) and surgical resection are unavailable. Given the potential differences in treatment effectiveness and side-effects, we sought to determine the associations between treatment type, decision regret and depression. MATERIALS AND METHODS: A multicentre, prospective study of patients with stage IA-IIA non-small cell lung cancer (NSCLC) with planned treatment with SBRT or surgical resection was conducted. Decision regret and depression were measured using the Decision Regret Scale (DRS) and Patient Health Questionnaire-4 (PHQ-4) at 3, 6 and 12 months post-treatment, respectively. Mixed linear regression modelling examined associations between treatment and decision regret adjusting for patient sociodemographics. RESULTS: Among 211 study participants with early-stage lung cancer, 128 (61%) patients received SBRT and 83 (39%) received surgical resection. The mean age was 73 years (standard deviation = 8); 57% were female; 79% were White non-Hispanic. In the entire cohort at 3 months post-treatment, 72 (34%) and 57 (27%) patients had mild and severe decision regret, respectively. Among patients who received SBRT or surgery, 71% and 46% of patients experienced at least mild decision regret at 3 months, respectively. DRS scores increased at 6 months and decreased slightly at 12 months of follow-up in both groups. Higher DRS scores were associated with SBRT treatment (adjusted mean difference = 4.18, 95% confidence interval 0.82 to 7.54) and depression (adjusted mean difference = 3.49, 95% confidence interval 0.52 to 6.47). Neither patient satisfaction with their provider nor decision-making role concordance was associated with DRS scores. CONCLUSIONS: Most early-stage lung cancer patients experienced at least mild decision regret, which was associated with SBRT treatment and depression symptoms. Findings suggest patients with early-stage lung cancer may not be receiving optimal treatment decision-making support. Therefore, opportunities for improved patient-clinician communication probably exist.


Sujet(s)
Carcinome pulmonaire non à petites cellules , Tumeurs du poumon , Radiochirurgie , Humains , Femelle , Sujet âgé , Mâle , Carcinome pulmonaire non à petites cellules/radiothérapie , Carcinome pulmonaire non à petites cellules/chirurgie , Carcinome pulmonaire non à petites cellules/anatomopathologie , Tumeurs du poumon/radiothérapie , Tumeurs du poumon/chirurgie , Tumeurs du poumon/anatomopathologie , Études prospectives , Résultat thérapeutique , Radiochirurgie/effets indésirables , Émotions , Stadification tumorale
2.
Ann Vasc Surg ; 42: 214-221, 2017 Jul.
Article de Anglais | MEDLINE | ID: mdl-28389293

RÉSUMÉ

BACKGROUND: Cigarette smoking is strongly associated with atherosclerotic disease. It is incumbent on vascular surgeons to provide smoking cessation counseling (SCC) to their patients. The objective of this study was to determine the association of SCC and improvement in quality of care. METHODS: As a quality project using retrospective data, the study received institutional review board exemption status. A retrospective review of prospectively maintained database from April 2014 through March 2015 of outpatient encounters in a vascular surgery clinic was performed of current smokers. Through the quality support team, providers were encouraged to counsel smokers to quit, document the discussion, and bill specific Evaluate and Management codes (99406 and 99407). The number of outpatients by smoking status, documentation and billing of SCC, demographics of current smokers, and monetary collections were collected. Data were compared using a correlation coefficient calculated and tested for statistical significant using two-tailed t-test. RESULTS: A sample of 1,077 visits by 612 currently smoking patients accounted for 24% of all outpatient vascular surgery visits. The average age was 61 years, and 64% were male. Comorbidities included 77% with hypertension, 32% with diabetes mellitus, and 14% with chronic kidney disease. Medically, 72% were on aspirin, 71% on statin, and 48% on beta blocker. A total of 208 (34%) never underwent a vascular intervention, and 183 (30%) had an intervention during the study period (44% for peripheral artery disease, 10% for carotid stenosis, 14% amputations, and 10% abdominal aortic aneurysm). Documentation improved from 65% of encounters during the first month to 89% in the peak month and 79% of total encounters. All-cause mortality rate was 2%, and this cohort demonstrated 75% SCC for 28 encounters. Fifty-five patients (9%) quit smoking for more than 30 days at the end of the study period, and this cohort had 69% of their 97 encounters with documented SCC. Increased SCC was correlated with decreased 30-day readmissions during the concurrent month (r = -0.711, P = 0.009) and the following month (r = -0.719, P = 0.008). There was a weak correlation with decreased amputations the following month (r = -0.5, P = 0.08). From a financial perspective, $1,373 was collected for 33 patients with a potential for collection of $7,460 predicted for minimum Medicare payment of 1 visit per patient. CONCLUSIONS: Advising vascular patients in the arduous process of smoking cessation benefits both the patient and the health system. Proper documentation and billing decreases costs of early readmissions and increases departmental revenue.


Sujet(s)
Assistance/économie , /économie , Amélioration de la qualité/économie , Indicateurs qualité santé/économie , Arrêter de fumer/économie , Maladies vasculaires/économie , Maladies vasculaires/chirurgie , Procédures de chirurgie vasculaire/économie , Sujet âgé , Sujet âgé de 80 ans ou plus , Comorbidité , Économies , Analyse coût-bénéfice , Bases de données factuelles , Frais et honoraires , Femelle , Coûts des soins de santé , Humains , Revenu , Mâle , Adulte d'âge moyen , Études rétrospectives , Facteurs de risque , Fumer/effets indésirables , Fumer/économie , Arrêter de fumer/méthodes , Résultat thérapeutique , Maladies vasculaires/diagnostic , Maladies vasculaires/mortalité , Procédures de chirurgie vasculaire/effets indésirables , Procédures de chirurgie vasculaire/mortalité
3.
Clin Exp Immunol ; 173(3): 512-22, 2013 Sep.
Article de Anglais | MEDLINE | ID: mdl-23668840

RÉSUMÉ

In this study, we hypothesized that the granulomatous disorder sarcoidosis is not caused by a single pathogen, but rather results from abnormal responses of Toll-like receptors (TLRs) to conserved bacterial elements. Unsorted bronchoalveolar lavage (BAL) cells from patients with suspected pulmonary sarcoidosis and healthy non-smoking control subjects were stimulated with representative ligands of TLR-2 (in both TLR-2/1 and TLR-2/6 heterodimers) and TLR-4. Responses were determined by assessing resulting production of tumour necrosis factor (TNF)-α and interleukin (IL)-6. BAL cells from patients in whom sarcoidosis was confirmed displayed increased cytokine responses to the TLR-2/1 ligand 19-kDa lipoprotein of Mycobacterium tuberculosis (LpqH) and decreased responses to the TLR-2/6 agonist fibroblast stimulating ligand-1 (FSL)-1. Subsequently, we evaluated the impact of TLR-2 gene deletion in a recently described murine model of T helper type 1 (Th1)-associated lung disease induced by heat-killed Propionibacterium acnes. As quantified by blinded scoring of lung pathology, P. acnes-induced granulomatous pulmonary inflammation was markedly attenuated in TLR-2(-/-) mice compared to wild-type C57BL/6 animals. The findings support a potential role for disordered TLR-2 responses in the pathogenesis of pulmonary sarcoidosis.


Sujet(s)
Sarcoïdose pulmonaire/métabolisme , Récepteur de type Toll-2/métabolisme , Adolescent , Adulte , Sujet âgé , Animaux , Liquide de lavage bronchoalvéolaire/cytologie , Liquide de lavage bronchoalvéolaire/immunologie , Études cas-témoins , Cytokines/biosynthèse , Modèles animaux de maladie humaine , Femelle , Expression des gènes , Humains , Ligands , Mâle , Souris , Souris knockout , Adulte d'âge moyen , Pneumopathie infectieuse/génétique , Pneumopathie infectieuse/immunologie , Propionibacterium acnes/immunologie , Multimérisation de protéines , Sarcoïdose pulmonaire/génétique , Sarcoïdose pulmonaire/immunologie , Récepteur de type Toll-2/antagonistes et inhibiteurs , Récepteur de type Toll-2/génétique , Récepteur de type Toll-4/agonistes , Récepteur de type Toll-4/métabolisme , Récepteurs de type Toll/composition chimique , Récepteurs de type Toll/génétique , Récepteurs de type Toll/métabolisme , Jeune adulte
4.
Thorac Cardiovasc Surg ; 59(2): 119-20, 2011 Mar.
Article de Anglais | MEDLINE | ID: mdl-21384309

RÉSUMÉ

Endovascular abdominal aortic aneurysm repair in decompensated heart failure patients requiring ventricular assist device (VAD) placement needs careful consideration of both complex disease states. We present this clinical dilemma and describe our choice of transcatheter aneurysm repair in the face of advanced refractory heart failure following VAD implantation.


Sujet(s)
Anévrysme de l'aorte abdominale/chirurgie , Implantation de prothèses vasculaires , Procédures endovasculaires , Défaillance cardiaque/thérapie , Transplantation cardiaque , Dispositifs d'assistance circulatoire , Anévrysme de l'aorte abdominale/complications , Défaillance cardiaque/complications , Humains , Mâle , Adulte d'âge moyen , Résultat thérapeutique , Listes d'attente
5.
Br J Surg ; 97(12): 1784-9, 2010 Dec.
Article de Anglais | MEDLINE | ID: mdl-20730858

RÉSUMÉ

BACKGROUND: This study evaluated the safety and haemostatic effectiveness of a fibrin sealant (EVICEL(™) Fibrin Sealant (Human)) during vascular surgery. METHODS: This prospective randomized controlled trial compared the haemostatic effectiveness of fibrin sealant (75 patients) or manual compression (72) in polytetrafluoroethylene (PTFE) arterial anastomoses. The primary endpoint was the absence of bleeding at the anastomosis at 4 min after randomization. Secondary endpoints included haemostasis at 7 and 10 min, treatment failures and the incidence of complications potentially related to bleeding. Adverse events were recorded. RESULTS: A higher percentage of patients who received fibrin sealant versus manual compression achieved haemostasis at 4 min (85 versus 39 per cent respectively; odds ratio 11·34, 95 per cent confidence interval 4·67 to 27·52; P < 0·001). Similarly, a higher percentage of patients who received fibrin sealant achieved haemostasis at 7 and 10 min (both P < 0·001). The incidence of treatment failure was lower in the fibrin sealant group (P < 0·001). The rate of complications potentially related to bleeding was similar (P = 0·426). Some 64 per cent of patients who received fibrin sealant experienced at least one adverse event, compared with 71 per cent who received manual compression. CONCLUSION: This fibrin sealant was safe, and significantly shortened the time to haemostasis in vascular procedures using PTFE. REGISTRATION NUMBER: NCT00154141 (http://www.clinicaltrials.gov).


Sujet(s)
Colle de fibrine/usage thérapeutique , Hémostase chirurgicale/méthodes , Hémostatiques/usage thérapeutique , Acide tranéxamique/effets indésirables , Procédures de chirurgie vasculaire/effets indésirables , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Anastomose chirurgicale , Bandages de compression , Femelle , Colle de fibrine/effets indésirables , Hémostatiques/effets indésirables , Humains , Mâle , Adulte d'âge moyen , Études prospectives , Résultat thérapeutique , Royaume-Uni , États-Unis
6.
Oncogene ; 28(4): 518-33, 2009 Jan 29.
Article de Anglais | MEDLINE | ID: mdl-19015641

RÉSUMÉ

Targeted therapy against epidermal growth factor receptor (EGFR) represents a major therapeutic advance in lung cancer treatment. Somatic mutations of the EGFR gene, most commonly L858R (exon 21) and short in-frame exon 19 deletions, have been found to confer enhanced sensitivity toward the inhibitors gefitinib and erlotinib. We have recently identified an EGFR mutation E884K, in combination with L858R, in a patient with advanced lung cancer who progressed on erlotinib maintenance therapy, and subsequently had leptomeningeal metastases that responded to gefitinib. The somatic E884K substitution appears to be relatively infrequent and resulted in a mutant lysine residue that disrupts an ion pair with residue R958 in the EGFR kinase domain C-lobe, an interaction that is highly conserved within the human kinome as demonstrated by our sequence analysis and structure analysis. Our studies here, using COS-7 transfection model system, show that E884K works in concert with L858R in-cis, in a dominant manner, to change downstream signaling, differentially induce Mitogen-activated protein kinase (extracellular signaling-regulated kinase 1/2) signaling and associated cell proliferation and differentially alter sensitivity of EGFR phosphorylation inhibition by ERBB family inhibitors in an inhibitor-specific manner. Mutations of the conserved ion pair E884-R958 may result in conformational changes that alter kinase substrate recognition. The analogous E1271K-MET mutation conferred differential sensitivity toward preclinical MET inhibitors SU11274 (unchanged) and PHA665752 (more sensitive). Systematic bioinformatics analysis of the mutation catalog in the human kinome revealed the presence of cancer-associated mutations involving the conserved E884 homologous residue, and adjacent residues at the ion pair, in known proto-oncogenes (KIT, RET, MET and FAK) and tumor-suppressor gene (LKB1). Targeted therapy using small-molecule inhibitors should take into account potential cooperative effects of multiple kinase mutations, and their specific effects on downstream signaling and inhibitor sensitivity. Improved efficacy of targeted kinase inhibitors may be achieved by targeting the dominant activating mutations present.


Sujet(s)
Récepteurs ErbB/génétique , Récepteurs ErbB/métabolisme , Tumeurs du poumon/enzymologie , Tumeurs du poumon/génétique , Système de signalisation des MAP kinases/génétique , Mutation faux-sens , AMP-activated protein kinase kinases , Substitution d'acide aminé , Animaux , Cellules COS , Chlorocebus aethiops , Récepteurs ErbB/antagonistes et inhibiteurs , Chlorhydrate d'erlotinib , Focal adhesion kinase 1/antagonistes et inhibiteurs , Focal adhesion kinase 1/génétique , Focal adhesion kinase 1/métabolisme , Humains , Indoles/pharmacologie , Tumeurs du poumon/traitement médicamenteux , Tumeurs du poumon/anatomopathologie , Système de signalisation des MAP kinases/effets des médicaments et des substances chimiques , Mitogen-Activated Protein Kinase 1/antagonistes et inhibiteurs , Mitogen-Activated Protein Kinase 1/génétique , Mitogen-Activated Protein Kinase 1/métabolisme , Mitogen-Activated Protein Kinase 3/antagonistes et inhibiteurs , Mitogen-Activated Protein Kinase 3/génétique , Mitogen-Activated Protein Kinase 3/métabolisme , Pipérazines/pharmacologie , Conformation des protéines , Inhibiteurs de protéines kinases/pharmacologie , Inhibiteurs de protéines kinases/usage thérapeutique , Protein-Serine-Threonine Kinases/antagonistes et inhibiteurs , Protein-Serine-Threonine Kinases/génétique , Protein-Serine-Threonine Kinases/métabolisme , Protéines proto-oncogènes/antagonistes et inhibiteurs , Protéines proto-oncogènes/génétique , Protéines proto-oncogènes/métabolisme , Protéines proto-oncogènes c-kit/génétique , Protéines proto-oncogènes c-kit/métabolisme , Protéines proto-oncogènes c-met , Protéines proto-oncogènes c-ret/antagonistes et inhibiteurs , Protéines proto-oncogènes c-ret/génétique , Protéines proto-oncogènes c-ret/métabolisme , Quinazolines/pharmacologie , Quinazolines/usage thérapeutique , Récepteur facteur croissance/antagonistes et inhibiteurs , Récepteur facteur croissance/génétique , Récepteur facteur croissance/métabolisme , Sulfonamides/pharmacologie
7.
Br J Cancer ; 99(6): 911-22, 2008 Sep 16.
Article de Anglais | MEDLINE | ID: mdl-19238632

RÉSUMÉ

Despite clinical approval of erlotinib, most advanced lung cancer patients are primary non-responders. Initial responders invariably develop secondary resistance, which can be accounted for by T790M-EGFR mutation in half of the relapses. We show that MET is highly expressed in lung cancer, often concomitantly with epidermal growth factor receptor (EGFR), including H1975 cell line. The erlotinib-resistant lung cancer cell line H1975, which expresses L858R/T790M-EGFR in-cis, was used to test for the effect of MET inhibition using the small molecule inhibitor SU11274. H1975 cells express wild-type MET, without genomic amplification (CNV = 1.1). At 2 microM, SU 11274 had significant in vitro pro-apoptotic effect in H1975 cells, 3.9-fold (P = 0.0015) higher than erlotinib, but had no effect on the MET and EGFR-negative H520 cells. In vivo, SU11274 also induced significant tumour cytoreduction in H1975 murine xenografts in our bioluminescence molecular imaging assay. Using small-animal microPET/MRI, SU11274 treatment was found to induce an early tumour metabolic response in H1975 tumour xenografts. MET and EGFR pathways were found to exhibit collaborative signalling with receptor cross-activation, which had different patterns between wild type (A549) and L858R/T790M-EGFR (H1975). SU11274 plus erlotinib/CL-387,785 potentiated MET inhibition of downstream cell proliferative survival signalling. Knockdown studies in H1975 cells using siRNA against MET alone, EGFR alone, or both, confirmed the enhanced downstream inhibition with dual MET-EGFR signal path inhibition. Finally, in our time-lapse video-microscopy and in vivo multimodal molecular imaging studies, dual SU11274-erlotinib concurrent treatment effectively inhibited H1975 cells with enhanced abrogation of cytoskeletal functions and complete regression of the xenograft growth. Together, our results suggest that MET-based targeted inhibition using small-molecule MET inhibitor can be a potential treatment strategy for T790M-EGFR-mediated erlotinib-resistant non-small-cell lung cancer. Furthermore, optimised inhibition may be further achieved with MET inhibition in combination with erlotinib or an irreversible EGFR-TKI.


Sujet(s)
Résistance aux médicaments antinéoplasiques , Récepteurs ErbB/antagonistes et inhibiteurs , Indoles/usage thérapeutique , Tumeurs du poumon/traitement médicamenteux , Pipérazines/usage thérapeutique , Protéines proto-oncogènes/antagonistes et inhibiteurs , Quinazolines/usage thérapeutique , Récepteur facteur croissance/antagonistes et inhibiteurs , Sulfonamides/usage thérapeutique , Animaux , Association de médicaments , Récepteurs ErbB/métabolisme , Chlorhydrate d'erlotinib , Humains , Immunotransfert , Immunoprécipitation , Luciferases/métabolisme , Tumeurs du poumon/métabolisme , Tumeurs du poumon/anatomopathologie , Imagerie par résonance magnétique , Souris , Souris nude , Tomographie par émission de positons , Protéines proto-oncogènes/métabolisme , Protéines proto-oncogènes c-met , Petit ARN interférent/pharmacologie , Récepteur facteur croissance/métabolisme , Tests d'activité antitumorale sur modèle de xénogreffe
8.
Bone Marrow Transplant ; 38(11): 733-8, 2006 Dec.
Article de Anglais | MEDLINE | ID: mdl-17028624

RÉSUMÉ

Umbilical cord blood transplant (UCBT) has emerged as an alternate source of stem cells for transplantation in patients with hematologic malignancies. However, outcomes of adult UCBT patients requiring ICU admission remain unknown. In order to identify predictors of ICU transfer and mortality in UCBT patients, the course and outcome of all adult (> or = 16 years old) patients who underwent UCBT between 1 January 1998 and 31 December 2003 at University Hospitals of Cleveland were analyzed. Forty-four patients underwent UCBT during the study period and 25 (57%) required ICU transfer. Use of a myeloablative preparative regimen was a significant predictor of ICU transfer (P = 0.03). An infusion of higher numbers of nucleated cells was protective from ICU transfer (P = 0.05). For those patients transferred to the ICU, mortality was 72%. The univariate predictors of mortality, at the time of ICU admission were a high APACHE III score (P = 0.0004), use of vasopressors (P = 0.03), and a low platelet count (P = 0.03). We conclude that transfer of UCBT patients to an ICU may be predicted by their preparative regimen, while ICU mortality may be predicted by physiologic parameters upon admission.


Sujet(s)
Transplantation de cellules souches de sang du cordon/effets indésirables , Tumeurs hématologiques/thérapie , Unités de soins intensifs , Indice APACHE , Adolescent , Adulte , Sujet âgé , Transplantation de cellules souches de sang du cordon/mortalité , Femelle , Hôpitaux universitaires/statistiques et données numériques , Humains , Mâle , Adulte d'âge moyen , Agonistes myélo-ablatifs/effets indésirables , Admission du patient/statistiques et données numériques , Numération des plaquettes , Pronostic , Études rétrospectives , Facteurs de risque , Analyse de survie , Thrombopénie , Transplantation homologue , Résultat thérapeutique , Vasoconstricteurs/usage thérapeutique
9.
J Appl Physiol (1985) ; 101(6): 1795-802, 2006 Dec.
Article de Anglais | MEDLINE | ID: mdl-16888052

RÉSUMÉ

The objective of the present study was to examine the impact of early stages of lung injury on ventilatory control by hypoxia and hypercapnia. Lung injury was induced with intratracheal instillation of bleomycin (BM; 1 unit) in adult, male Sprague-Dawley rats. Control animals underwent sham surgery with saline instillation. Five days after the injections, lung injury was present in BM-treated animals as evidenced by increased neutrophils and protein levels in bronchoalveolar lavage fluid, as well as by changes in lung histology and computed tomography images. There was no evidence of pulmonary fibrosis, as indicated by lung collagen content. Basal core body temperature, arterial Po(2), and arterial Pco(2) were comparable between both groups of animals. Ventilatory responses to hypoxia (12% O(2)) and hypercapnia (7% CO(2)) were measured by whole body plethysmography in unanesthetized animals. Baseline respiratory rate and the hypoxic ventilatory response were significantly higher in BM-injected compared with control animals (P = 0.003), whereas hypercapnic ventilatory response was not statistically different. In anesthetized, spontaneously breathing animals, response to brief hyperoxia (Dejours' test, an index of peripheral chemoreceptor sensitivity) and neural hypoxic ventilatory response were augmented in BM-exposed relative to control animals, as measured by diaphragmatic electromyelograms. The enhanced hypoxic sensitivity persisted following bilateral vagotomy, but was abolished by bilateral carotid sinus nerve transection. These data demonstrate that afferent sensory input from the carotid body contributes to a selective enhancement of hypoxic ventilatory drive in early lung injury in the absence of pulmonary fibrosis and arterial hypoxemia.


Sujet(s)
Glomus carotidien/physiopathologie , Cellules chimioréceptrices/physiopathologie , Hypoxie/physiopathologie , Échanges gazeux pulmonaires , Réflexe , /physiopathologie , Maladie aigüe , Animaux , Hypoxie/complications , Mâle , Rats , Rat Sprague-Dawley , /complications
10.
Neuroscience ; 141(4): 2029-39, 2006 Sep 15.
Article de Anglais | MEDLINE | ID: mdl-16777350

RÉSUMÉ

Activation of the adenosine A(2A) receptor (A(2A)R) at the time of reperfusion has been shown to reduce ischemia-reperfusion injury in peripheral tissues and spinal cord. In this study we show that treating mice with the A(2A)R agonist, 4-{3-[6-amino-9-(5-cyclopropylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-piperidine-1-carboxylic acid methyl ester for four days beginning before or just after the onset of reperfusion after compression-induced spinal cord injury rapidly (within 1 day) and persistently (>42 days) reduces locomotor dysfunction and spinal cord demyelination. Protection is abolished in knockout/wild type bone marrow chimera mice selectively lacking the A(2A)R only on bone marrow-derived cells but retaining receptors on other tissues including blood vessels. Paradoxically, reduced spinal cord injury is also noted in A(2A)R -/- mice, and in wild type/knockout bone marrow chimera mice selectively lacking the A(2A)R on non-bone marrow-derived cells, or in mice treated with the A(2A) antagonist, 4-(2-[7-amino-2-[2-furyl][1,2,4]triazolo[2,3-a][1,3,5]triazin-5-yl-amino]ethyl)phenol. The greatest protection is seen in knockout/wild type bone marrow chimera mice treated with 4-{3-[6-amino-9-(5-cyclopropylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-piperidine-1-carboxylic acid methyl ester, i.e. by activating the A(2A)R in mice expressing the receptor only in bone marrow-derived cells. The data suggest that inflammatory bone marrow-derived cells are the primary targets of A(2A) agonist-mediated protection. We conclude that A(2A) agonists or other interventions that inhibit inflammation during and after spinal cord ischemia may be effective in reducing spinal cord injury in patients, but excessive or prolonged stimulation of the A(2A)R may be counterproductive. It may be possible to devise strategies to produce optimal spinal cord protection by exploiting temporal differences in A(2A)R-mediated responses.


Sujet(s)
Cellules de la moelle osseuse/métabolisme , Transplantation de moelle osseuse/méthodes , Récepteur A2A à l'adénosine/génétique , Récepteur A2A à l'adénosine/métabolisme , Syndrome de compression médullaire/métabolisme , Syndrome de compression médullaire/thérapie , Agonistes des récepteurs A2 à l'adénosine , Analyse de variance , Animaux , Modèles animaux de maladie humaine , Relation dose-effet des médicaments , Activation enzymatique/effets des médicaments et des substances chimiques , Femelle , Souris , Souris knockout , Activité motrice/effets des médicaments et des substances chimiques , Activité motrice/physiologie , Gaine de myéline/anatomopathologie , Pipéridines/composition chimique , Pipéridines/pharmacologie , Dosage par compétition/méthodes , Syndrome de compression médullaire/anatomopathologie , Syndrome de compression médullaire/physiopathologie , Facteurs temps , Triazines/pharmacocinétique , Triazoles/pharmacocinétique
11.
Abdom Imaging ; 29(4): 507-10, 2004.
Article de Anglais | MEDLINE | ID: mdl-15136894

RÉSUMÉ

Primary aortic angiosarcomas are extremely rare. Clinically and radiographically, they mimic atherosclerosis and atheroembolic disease. For a definitive diagnosis, histologic evaluation of the tumor or of peripheral emboli is required. The imaging findings are frequently nonspecific and in most published cases did not allow a definitive preoperative diagnosis. This is the first report of the computed tomographic angiographic findings of a primary intimal abdominal aortic sarcoma and a review of previously described imaging findings in these tumors.


Sujet(s)
Aorte abdominale/imagerie diagnostique , Maladies de l'aorte/diagnostic , Coronarographie/méthodes , Hémangiosarcome/diagnostic , Tomodensitométrie/méthodes , Tumeurs vasculaires/diagnostic , Aorte abdominale/anatomopathologie , Aorte abdominale/chirurgie , Maladies de l'aorte/traitement médicamenteux , Maladies de l'aorte/chirurgie , Aortographie , Diagnostic différentiel , Embolie de cholestérol/diagnostic , Issue fatale , Hémangiosarcome/traitement médicamenteux , Hémangiosarcome/chirurgie , Humains , Mâle , Adulte d'âge moyen , Tumeurs vasculaires/traitement médicamenteux , Tumeurs vasculaires/chirurgie , Vascularite/diagnostic
12.
J Heart Lung Transplant ; 20(12): 1291-6, 2001 Dec.
Article de Anglais | MEDLINE | ID: mdl-11744412

RÉSUMÉ

BACKGROUND: Reperfusion injury is the most common cause of early mortality following lung transplantation. Although cold graft ischemic time has been reported to influence this injury, some lung grafts with short ischemic times develop significant reperfusion injury, whereas other grafts with more prolonged ischemic times do not develop injury. Our hypothesis was that ischemic time did not significantly influence reperfusion injury or other outcomes following lung transplantation. METHODS: Data on 136 patients who had lung transplantation over a 10 year period was used for analysis. RESULTS: Cold graft ischemic time > or = 6 hours did not increase the risk of reperfusion injury, acute rejection, cytomegalovirus infection, bacterial or fungal pneumonia, bronchiolitis obliterans syndrome, 1-month mortality, 1-year mortality, or 5-year mortality compared with ischemic times of either < 4 hours or 4 to 6 hours. The incidence of reperfusion injury was at least 20% for each time group. CONCLUSIONS: At least 20% of all patients will develop reperfusion injury regardless of cold graft ischemic time. Prolonged ischemic times up to 8 hours do not result in a significant increase in adverse short-term, intermediate, or long-term outcomes. Cautious extension of ischemic time beyond the current target of 4 to 6 hours may be warranted for geographic expansion of the donor lung pool.


Sujet(s)
Cryoconservation , Transplantation pulmonaire/physiologie , Poumon/vascularisation , Conservation d'organe , Lésion d'ischémie-reperfusion/étiologie , Adolescent , Adulte , Sujet âgé , Enfant , Femelle , Rejet du greffon/étiologie , Rejet du greffon/mortalité , Humains , Mâle , Adulte d'âge moyen , Infections opportunistes/étiologie , Infections opportunistes/mortalité , Lésion d'ischémie-reperfusion/mortalité , Études rétrospectives , Facteurs de risque , Taux de survie
14.
Ann Thorac Surg ; 72(4): 1298-305, 2001 Oct.
Article de Anglais | MEDLINE | ID: mdl-11605614

RÉSUMÉ

BACKGROUND: Heart transplantation is an established therapy for cardiomyopathy but is limited by organ shortage and expense. As a result, alternative operations have been proposed including coronary bypass, mitral valve repair, and left ventricular reconstruction. Because it is unknown whether alternative operations are less expensive than replacing the diseased heart, we compared in-hospital costs and early outcome of these operations with elective heart transplantation. METHODS: We compared clinical and financial data of 268 patients with ejection fraction less than 30% who underwent elective heart transplantation (n = 52, UNOS status 2 only), coronary bypass (n = 176), mitral repair (n = 15), or left ventricular reconstruction (n = 25). Data were evaluated for between-group differences, with p less than 0.05 as significant. RESULTS: Preoperative ejection fraction, although similar for heart transplantation (21.2% +/- 1.3%), coronary bypass (25.8% +/- 0.4%), mitral repair (22.9% +/- 1.5%), and left ventricular reconstruction (24.2% +/- 2.1%), was significantly different between the former two (p < 0.001). There was no difference in operative mortality: 5.8% (3 of 52), 3.4% (7 of 176), 6.7% (1 of 15), and 4.0% (1 of 25), respectively (p = 0.8). However, total hospital cost of heart transplantation was significantly greater than all others: $75,992 +/- $5,380, $25,008 +/- $1,446, $32,375 +/- $2,379, and $26,584 +/- $4,076, respectively (p < 0.001). Organ procurement expenses alone comprised 39.7% ($30,169) of total transplant cost. Kaplan-Meier survival analysis failed to show any survival difference between the various groups (p = 0.86) CONCLUSIONS: Compared with heart transplantation, alternative operations yield a comparable early outcome and long-term survival, and are markedly less expensive. The cost of transplantation, which is largely due to procurement expenses, is yet another reason to attempt alternative operations for cardiomyopathy whenever feasible.


Sujet(s)
Cardiomyopathies/économie , Pontage aortocoronarien/économie , Transplantation cardiaque/économie , Coûts hospitaliers/statistiques et données numériques , Insuffisance mitrale/économie , Dysfonction ventriculaire gauche/économie , Sujet âgé , Cardiomyopathies/mortalité , Cardiomyopathies/chirurgie , Analyse coût-bénéfice , Femelle , Humains , Durée du séjour/économie , Mâle , Adulte d'âge moyen , Valve atrioventriculaire gauche/chirurgie , Insuffisance mitrale/chirurgie , Complications postopératoires/économie , Complications postopératoires/mortalité , Taux de survie , Dysfonction ventriculaire gauche/chirurgie
15.
Vasc Surg ; 35(4): 251-6; discussion 257, 2001.
Article de Anglais | MEDLINE | ID: mdl-11586450

RÉSUMÉ

Recent literature advocates carotid endarterectomy on duplex alone. The authors hypothesized that carotid angiography adds information that alters clinical management in a substantial number of patients compared to the use of carotid duplex examination alone. The records of 182 consecutive patients who underwent carotid artery duplex and subsequent carotid/cerebral angiography for suspected carotid artery stenosis between January 1998 and April 1999 were reviewed retrospectively. Carotid artery duplex examinations were stratified based on stenosis: < or =39%, 40% to 59%, 60% to 79% (moderate), 80% to 99% (severe), 100%. Carotid stenosis on angiograms was determined by NASCET criteria. New information found at angiography included vertebral, subclavian, or arch atherosclerosis, intracranial pathosis, or a change in duplex stenosis category to a degree of stenosis not requiring surgery. Clinical importance was attributed to angiograms that altered the patients' management plan. Angiography provided additional information in 53% (97/182) of patients. Vertebral disease was found in 25.1%, subclavian disease in 16.4%, intracranial disease in 15.3%, aortic arch disease in 3.3%. Patient treatment was altered in 30% (55/182). Angiographic findings downgraded the stenosis to medical therapy in 20.9% (38/182). The surgical plan was influenced in 5.5% (10/182). Nine intracranial aneurysms were discovered. Carotid angiography was essential for vascular bypass surgery planning in 3.3% (6/182). Angioplasty was performed in 2.2% (4/182). The accurate determination of stenosis is critical in determining optimal treatment of patients with carotid artery stenosis. Routine carotid angiography remains valuable in the clinical treatment of these patients.


Sujet(s)
Angiographie , Artères carotides/imagerie diagnostique , Sténose carotidienne/imagerie diagnostique , Sténose carotidienne/diagnostic , Sujet âgé , Angioplastie par ballonnet , Sténose carotidienne/thérapie , Femelle , Humains , Anévrysme intracrânien/diagnostic , Mâle , Échographie-doppler duplex
16.
Ann Thorac Surg ; 72(4): 1245-50, 2001 Oct.
Article de Anglais | MEDLINE | ID: mdl-11603444

RÉSUMÉ

BACKGROUND: The adenosine A2A agonist ATL-146e (4-[3-[6-Amino-9-(5-ethylcarbamoyl-3,4-dihydroxytetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl]-cyclohexanecarboxylic acid methyl ester) has been shown to prevent reperfusion injury in multiple organ systems through inhibition of activated leukocyte-endothelial interaction. We hypothesized that systemic ATL-146e could reduce spinal cord reperfusion injury after aortic clamping. METHODS: Twenty-six rabbits underwent cross-clamping of the infrarenal aorta for 45 minutes. One group received intravenous ATL-146e for 3 hours during reperfusion. A second cohort received only vehicle and served as controls. Animals were assessed at 24 and 48 hours using the Tarlov (0 to 5) scoring system for hind limb function. To evaluate neuronal attrition, immunostaining of lumbar spinal cord sections was performed using anti-SMI 33 antibody against neurofilament. RESULTS: Systemic ATL-146e was tolerated without hemodynamic lability. Animals that received ATL-146e had significantly improved neurologic outcomes 24 and 48 hours after spinal cord ischemia (p < 0.001). There was preservation of neuronal architecture in the ventral horn of spinal cord sections from animals receiving ATL-146e compared with control animals. CONCLUSIONS: Intravenous ATL-146e given during reperfusion is tolerated without hemodynamic lability, and results in substantially improved spinal cord function after ischemia by preservation of ventral horn neurons.


Sujet(s)
Acides cyclohexanecarboxyliques/pharmacologie , Agonistes des récepteurs purinergiques P1 , Purines/pharmacologie , Lésion d'ischémie-reperfusion/anatomopathologie , Ischémie de la moelle épinière/anatomopathologie , Animaux , Survie cellulaire/effets des médicaments et des substances chimiques , Examen neurologique/effets des médicaments et des substances chimiques , Neurones/effets des médicaments et des substances chimiques , Neurones/anatomopathologie , Lapins , Récepteur A2A à l'adénosine , Moelle spinale/effets des médicaments et des substances chimiques , Moelle spinale/anatomopathologie
17.
Lung Cancer ; 33(2-3): 115-23, 2001.
Article de Anglais | MEDLINE | ID: mdl-11551406

RÉSUMÉ

Several studies have suggested that non-small cell lung cancer (NSCLC) patients whose tumors have neuroendocrine (NE) features may be more responsive to chemotherapy. In addition, increased expression of p53 and HER2 may confer relative chemotherapy resistance and shortened survival. The Cancer and Leukemia Group B performed a series of studies involving sequential chemotherapy followed by radiation for patients with unresectable stage III NSCLC. The objectives of this study were to analyze pathological specimens using immunohistochemistry for NE markers, p53 and HER2 to determine if there was a correlation between marker expression and response or survival. Of 160 eligible patients, 28 (18%) were not evaluable because of inadequate material. The percentage of specimens positive for markers was as follows: neuron-specific enolase 38%, Leu-7 2%, chromogranin A 0%, synaptophysin 5%, > or =2+NE markers 3%, p53 61%, and HER2 65%. There was no statistically significant correlation between any individual marker and response to induction chemotherapy or response to combined chemotherapy/radiation except for synaptophysin. Six of 6 (100%) synaptophysin positive tumors responded by the completion of all therapy compared with 69/125 (55%) synaptophysin negative tumors (P=0.04). None of the individual markers had a significant effect on survival in univariate analysis. Neuron-specific enolase was marginally significant in multivariate analysis (P=0.08). In conclusion, this study did not demonstrate that expression of NE markers, p53 and HER2 were predictive of response to chemotherapy, combined chemotherapy/radiation or for survival in this group of patients with stage III NSCLC. Future studies must employ either different markers or be performed on more adequate surgical specimens.


Sujet(s)
Antinéoplasiques/usage thérapeutique , Marqueurs biologiques tumoraux/analyse , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Tumeurs du poumon/traitement médicamenteux , Récepteur ErbB-2/analyse , Protéine p53 suppresseur de tumeur/analyse , Antigène carcinoembryonnaire/analyse , Carcinome pulmonaire non à petites cellules/composition chimique , Carcinome pulmonaire non à petites cellules/classification , Association thérapeutique , Femelle , Humains , Tumeurs du poumon/composition chimique , Tumeurs du poumon/classification , Mâle , Adulte d'âge moyen , Stadification tumorale , Pronostic , Taux de survie
18.
J Vasc Surg ; 34(3): 482-8, 2001 Sep.
Article de Anglais | MEDLINE | ID: mdl-11533601

RÉSUMÉ

BACKGROUND: We hypothesized that systemic ATL-146e, an adenosine A(2A) agonist, would decrease spinal cord reperfusion inflammatory stress and inhibit apoptosis and that these effects would correlate with improved neurologic functional outcome. METHODS: Thirty rabbits underwent cross-clamping of the infrarenal aorta for 45 minutes. One group of animals (n = 14) received 0.06 microg/kg per minute of ATL-146e infused intravenously for 3 hours, beginning 15 minutes before reperfusion. A second group of animals (n = 16) underwent spinal cord ischemia with saline vehicle alone and served as ischemic controls. Animals (n = 9, 11) from each group survived for 48 hours and assessed for neurologic impairment with the Tarlov (0-5) scoring system. Four animals from each group were humanely killed at the end of the 3-hour treatment period, and the remainder killed after 48 hours' survival. In all animals, lumbar spinal cord tissue specimens were frozen for subsequent Western blot analysis of heat shock protein 70 (HSP 70), and for the p85 fragment of poly (ADP-ribose) polymerase (PARP). Neuronal viability indices were determined at 48 hours with hematoxylin and eosin staining. RESULTS: There was improvement in neurologic function in rabbits receiving ATL-146e (P <.001) compared with ischemic controls. At the end of the 3-hour treatment period there was a 46% (P <.05) decrease in HSP 70 expression in the ATL-146e group compared with the control group, but no difference in PARP expression. At 48 hours, there was no difference between control and ATL-146e groups in HSP 70 expression, but there was a 65% (P <.05) reduction in PARP in the spinal cords of animals that had received ATL-146e. There was a significant improvement in neuronal viability indices in animals receiving ATL-146e compared with ischemic controls (P <.05). CONCLUSIONS: Systemic ATL-146e infusion during reperfusion after spinal cord ischemia results in preservation of hindlimb motor function. There is evidence of decreased spinal cord inflammatory stress immediately after treatment with ATL-146e as indicated by reduced HSP 70 induction. Treatment with ATL-146e is associated with a reduction in neuronal apoptosis as suggested by a substantial decrease in the fragmentation of PARP at 48 hours. These results suggest that inflammation during reperfusion and subsequent apoptosis contribute to paralysis after restoration of blood flow to the ischemic spinal cord.


Sujet(s)
Apoptose/effets des médicaments et des substances chimiques , Acides cyclohexanecarboxyliques/pharmacologie , Ischémie/étiologie , Paralysie/prévention et contrôle , Agonistes des récepteurs purinergiques P1 , Purines/pharmacologie , Reperfusion/effets indésirables , Moelle spinale/vascularisation , Animaux , Ischémie/complications , Lapins , Récepteur A2A à l'adénosine
19.
J Vasc Surg ; 34(2): 367-8, 2001 Aug.
Article de Anglais | MEDLINE | ID: mdl-11496295

RÉSUMÉ

The proximal suture line is a vulnerable area after abdominal aortic aneurysm repairs. This area has been implicated in various postoperative complications, such as pseudoaneurysm formation, graft-enteric fistula, and suture line disruption. We present a technique that provides safe and adequate coverage of this suture line by using the aneurysm sac. This technique is derived from the z-plasty technique used for scar revision. The technique is illustrated with detailed line drawings. None of the patients in whom we used this technique have had any complications related to the proximal suture line.


Sujet(s)
Anévrysme de l'aorte abdominale/chirurgie , Techniques de suture , Humains
20.
Ann Thorac Surg ; 72(2): 380-5, 2001 Aug.
Article de Anglais | MEDLINE | ID: mdl-11515870

RÉSUMÉ

BACKGROUND: We hypothesized that compensatory lung growth after lobectomy is characterized by a combination of cellular hyperplasia and hypertrophy and that up-regulation of epidermal growth factor receptor (EGFR) is involved in these processes. METHODS: Age-matched mature pigs were divided into four groups. The control group (group C) did not have operation. Two groups underwent left upper lobectomy and were studied 2 weeks (group L2) or 3 months (group L3) later. The last group underwent a sham left thoracotomy, and the left lower lobe was harvested 2 weeks later for EGFR analysis. Left lower lobes were studied using wet weight, cell proliferation index through immunostaining for 5-bromo-2'-deoxyuridine, morphometry, and Western blot analysis for EGFR. Content of protein and DNA (deoxyribonucleic acid) in the lung tissue was also determined. RESULTS: Left lower lobe weights were elevated in both groups L2 and L3 compared with group C. We noted a significant rise in the proliferation index, with a concomitant increase in EGFR expression, in group L2 compared with group C. In group L3, there was an increase in the protein to DNA ratio compared with group C. CONCLUSIONS: We conclude that compensatory lung growth after lobectomy comprises an early increase in the cell proliferation index (ie, cellular hyperplasia) and a late increase in the protein to DNA ratio (ie, cellular hypertrophy). The early proliferative phase is associated with EGFR up-regulation.


Sujet(s)
Récepteurs ErbB/génétique , Poumon/croissance et développement , Pneumonectomie , Animaux , Division cellulaire/génétique , ADN/génétique , Expression des gènes , Poumon/anatomopathologie , Taille d'organe , Suidae , Porc miniature , Régulation positive/génétique
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