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1.
J Clin Pharm Ther ; 43(3): 366-376, 2018 Jun.
Article de Anglais | MEDLINE | ID: mdl-29468708

RÉSUMÉ

WHAT IS KNOWN AND OBJECTIVE: Drug therapies are critical for preventing secondary complications in acute coronary syndrome (ACS). The purpose of this study was to develop and apply a pharmaceutical care service (PCS) algorithm for ACS and confirm that it is applicable through a prospective clinical trial. METHODS: The ACS-PCS algorithm was developed according to extant evidence-based treatment and pharmaceutical care guidelines. Quality assurance was conducted through two methods: literature comparison and expert panel evaluation. The literature comparison was used to compare the content of the algorithm with the referenced guidelines. Expert evaluations were conducted by nine experts for 75 questionnaire items. A trial was conducted to confirm its effectiveness. Seventy-nine patients were assigned to either the pharmacist-included multidisciplinary team care (MTC) group or the usual care (UC) group. The endpoints of the trial were the prescription rate of two important drugs, readmission, emergency room (ER) visit and mortality. RESULTS AND DISCUSSION: The main frame of the algorithm was structured with three tasks: medication reconciliation, medication optimization and transition of care. The contents and context of the algorithm were compliant with class I recommendations and the main service items from the evidence-based guidelines. Opinions from the expert panel were mostly positive. There were significant differences in beta-blocker prescription rates in the overall period (P = .013) and ER visits (four cases, 9.76%, P = .016) in the MTC group compared to the UC group, respectively. WHAT IS NEW AND CONCLUSION: We developed a PCS algorithm for ACS based on the contents of evidence-based drug therapy and the core concept of pharmacist services.


Sujet(s)
Syndrome coronarien aigu/traitement médicamenteux , Équipe soignante/organisation et administration , Services pharmaceutiques/organisation et administration , Pharmaciens/organisation et administration , Syndrome coronarien aigu/mortalité , Antagonistes bêta-adrénergiques/administration et posologie , Adulte , Sujet âgé , Algorithmes , Service hospitalier d'urgences/statistiques et données numériques , Pratique factuelle/organisation et administration , Femelle , Humains , Mâle , Bilan comparatif des médicaments , Adulte d'âge moyen , Réadmission du patient/statistiques et données numériques , Guides de bonnes pratiques cliniques comme sujet , Études prospectives
3.
Gene Ther ; 23(3): 306-12, 2016 Mar.
Article de Anglais | MEDLINE | ID: mdl-26649448

RÉSUMÉ

VM202, a plasmid DNA that expresses two isoforms of hepatocyte growth factor, may elicit angiogenic effects that could benefit patients with critical limb ischemia (CLI). In a phase 2, double-blind trial in 52 CLI patients, we examined the safety and potential efficacy of intramuscular injections of low-dose (n=21) or high-dose (n=20) VM202 or placebo (n=11) in the affected limb (days 0, 14, 28 and 42). Adverse events and serious adverse events were similar among the groups; no malignancy or proliferative retinopathy was seen. In exploratory efficacy analyses, we found no differences in ankle or toe-brachial index, VAS, VascuQuol or amputation rate among the groups. Complete ulcer healing was significantly better in high-dose (8/13 ulcers; P<0.01) versus placebo (1/9) patients. Clinically meaningful reductions (>50%) in ulcer area occurred in high-dose (9/13 ulcers) and low-dose (19/27) groups versus placebo (1/9; P<0.05 and P<0.005, respectively). At 12 months, significant differences were seen in TcPO2 between the high-dose and placebo groups (47.5 ± 17.8 versus 36.6 ± 24.0 mm Hg, respectively; P<0.05) and in the change from baseline among the groups (P<0.05). These data suggest that VM202 is safe and may provide therapeutic bioactivity in CLI patients.


Sujet(s)
Membres/vascularisation , Membres/traumatismes , Vecteurs génétiques/effets indésirables , Facteur de croissance des hépatocytes/effets indésirables , Facteur de croissance des hépatocytes/génétique , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Plasmides/effets indésirables , Isoformes de protéines/effets indésirables , Isoformes de protéines/génétique
4.
Nutr Metab Cardiovasc Dis ; 24(11): 1240-5, 2014 Nov.
Article de Anglais | MEDLINE | ID: mdl-25096924

RÉSUMÉ

BACKGROUNDS AND AIMS: C-reactive protein (CRP) levels predict incident and recurrent cardiovascular disease (CVD) events; however, associations between CRP and pre-clinical atherosclerosis is less certain. Since high concentrations of high-density lipoprotein cholesterol (HDL-C) are inversely associated with CVD risk, we investigated whether HDL-C modified the association between CRP concentration and measures of preclinical atherosclerosis. METHODS AND RESULTS: Data were analyzed from a Korean occupational cohort of 12,030 male subjects who underwent a cardiac computed tomography (CT) estimation of coronary artery calcification (CAC) score and an assessment of CVD risk factors. Logistic regression was used to describe associations between CRP and measures of pre-clinical atherosclerosis, such as CAC scores >0. As many as 1351 (11.2%) participants had a CAC score>0. CRP was stratified into 3 groups based on clinical category: <1 mg/L, 1 to <2 mg/L, and ≥ 2 mg/dL. In the bottom CRP group, 907/8697 (10.4%) of subjects had a CAC score >0, compared with 242/1943 (12.5%) in the middle group and 202/1396 (14.5%) in the top CRP group (p < 0.0001). After adjustment for multiple CVD risk factors, there was a positive association between CRP and CAC score>0 (OR between top and bottom CRP groups, 1.41 [1.04, 1.90], p = 0.027) in the lowest HDL-C quartile but not in the highest HDL-C (OR between top and bottom CRP group, 0.80 [0.46, 1.39], p = 0.425). CONCLUSION: The association between CRP concentration and CAC score differed according to HDL-C levels.


Sujet(s)
Athérosclérose/sang , Protéine C-réactive/métabolisme , Calcium/sang , Cholestérol HDL/sang , Maladie des artères coronaires/sang , Adulte , Sujet âgé , Athérosclérose/diagnostic , Cholestérol LDL/sang , Études de cohortes , Maladie des artères coronaires/diagnostic , Études transversales , Volontaires sains , Humains , Modèles logistiques , Mâle , Adulte d'âge moyen , République de Corée , Enquêtes et questionnaires , Triglycéride/sang
5.
Gene Ther ; 17(12): 1442-52, 2010 Dec.
Article de Anglais | MEDLINE | ID: mdl-20668482

RÉSUMÉ

Hepatocyte growth factor (HGF) has been shown to induce angiogenesis in vivo and has potential as a candidate gene for 'therapeutic angiogenesis'. In vivo, two isoforms of HGF, HGF723 and HGF728, consisting of 723 and 728 amino acids, are generated through alternative splicing between exons 4 and 5, but the biological effects of their coexpression have not yet been elucidated. In this study, we generated a series of genomic-complementary DNA (cDNA) hybrids of the HGF gene by inserting various truncated intron 4 into the junction of exons 4 and 5 of HGF cDNA and analyzed the biological activities of these hybrid constructs. We showed that: (1) the hybrid called HGF-X7, which contained 1502 base pairs of intron 4, could drive a higher level of HGF expression than other hybrid constructs and cDNAs of each isoform alone; (2) the pCK vector was most efficient for the gene expression of HGF-X7; (3) coexpression of both isoforms of HGF could more efficiently induce the migration of human umbilical vein endothelial cell (HUVEC) and of the mouse myoblast cell line C2C12 myoblasts than a single isoform of HGF and human vascular endothelial growth factor (VEGF)165 at a given concentration; (4) intramuscular administration of pCK-HGF-X7 resulted in transient and localized HGF expression in the injected muscle without an increase in the HGF protein levels in other tissues including serum; and (5) intramuscular injection of pCK-HGF-X7 could more efficiently increase the number of angiographically recognizable collateral vessels, as well as improve an intra-arterial Doppler wire-measured blood flow in the rabbit model of hindlimb ischemia when compared with the identical vector encoding VEGF165 gene. These results showed that transfer of the genomic-cDNA hybrid of the HGF gene could be used as a potential therapeutic approach to human vascular diseases.


Sujet(s)
Artères , Circulation collatérale/effets des médicaments et des substances chimiques , ADN/usage thérapeutique , Thérapie génétique , Facteur de croissance des hépatocytes/génétique , Facteur de croissance des hépatocytes/métabolisme , Ischémie/thérapie , Animaux , Artères/croissance et développement , Artères/métabolisme , Lignée cellulaire , Mouvement cellulaire/effets des médicaments et des substances chimiques , ADN/génétique , ADN complémentaire/génétique , Modèles animaux de maladie humaine , Membres/vascularisation , Femelle , Expression des gènes , Techniques de transfert de gènes , Génie génétique , Vecteurs génétiques/génétique , Facteur de croissance des hépatocytes/pharmacologie , Humains , Introns/génétique , Ischémie/physiopathologie , Mâle , Souris , Souris de lignée BALB C , Isoformes de protéines/génétique , Isoformes de protéines/métabolisme , Lapins , Débit sanguin régional/effets des médicaments et des substances chimiques
6.
J Am Soc Echocardiogr ; 14(11): 1100-6, 2001 Nov.
Article de Anglais | MEDLINE | ID: mdl-11696835

RÉSUMÉ

Mitral stenosis (MS) and mitral regurgitation (MR) are the most frequent conditions that cause a dilation and dysfunction of the left atrial appendage (LAA). Despite similarly dilated LAA in patients with MS and MR, the incidence of LAA thrombi and the risk of thromboembolism is different between these patients. The purpose of this study was to characterize the filling pattern of LAA by using intravenous administration of perfluorocarbon-exposed dextrose albumin (PESDA) during transesophageal echocardiographic examination in patients with MS and MR. Twenty-four patients with moderate to severe MS, 12 patients with severe MR, and a control group including 30 patients with conditions other than mitral valve disease underwent transesophageal echocardiographic examination with an intravenous bolus injection of PESDA. LAA emptying and filling velocities and maximal and minimal areas of LAA and LAA ejection fraction were measured. Digital gray-scale intensity (GSI) of the left atrial (LA) and LAA cavity after PESDA injection was measured by off-line analysis. Compared with control patients, patients with MS or MR had larger maximal and minimal areas of LAA and reduced LAA ejection fraction. LAA peak emptying flow velocity was significantly lower in patients with MS compared with those of MR or control patients. LAA peak filling velocity was significantly lower in patients with MS compared with that of control patients. However, there was no significant difference of LAA peak filling velocity between the patients with MS and MR. There was no significant difference of GSI ratio of LAA and LA between patients with MR and control patients; however, GSI ratio of LAA and LA was significantly lower in patients with MS compared with that of MR. The incidence of LAA spontaneous echo contrast and LAA thrombi in patients with MS was significantly higher than that of the patients with MR and control subjects (P <.005). Despite similarly dilated LAA area and depressed contractile function of LAA in patients with MS and MR compared with control patients, profoundly impaired LAA filling with resultant flow stasis was demonstrated by contrast echocardiography in patients with MS. These findings may explain the higher incidence of LAA spontaneous echo contrast and thrombus in patients with MS.


Sujet(s)
Auricule de l'atrium/physiopathologie , Insuffisance mitrale/physiopathologie , Sténose mitrale/physiopathologie , Sujet âgé , Auricule de l'atrium/imagerie diagnostique , Études cas-témoins , Produits de contraste/administration et posologie , Thrombose coronarienne/étiologie , Thrombose coronarienne/physiopathologie , Échocardiographie transoesophagienne , Femelle , Fluorocarbones/administration et posologie , Glucose/administration et posologie , Humains , Injections veineuses , Mâle , Adulte d'âge moyen , Insuffisance mitrale/complications , Sténose mitrale/complications , Valeurs de référence , Sérumalbumine/administration et posologie , Sérum-albumine humaine , Débit systolique
7.
Am J Cardiol ; 87(5): 669-71, A11, 2001 Mar 01.
Article de Anglais | MEDLINE | ID: mdl-11230864

RÉSUMÉ

When the results of transesophageal echocardiography was regarded as the gold standard for detecting a patent foramen ovale (PFO) in 136 consecutive patients referred for evaluation of cardiac source of embolism, transthoracic harmonic imaging using saline contrast was superior to fundamental imaging in accuracy for detecting a PFO (sensitivity, 22.5%; specificity [p < 0.05] and sensitivity, 100%; specificity 100%, respectively.)


Sujet(s)
Échocardiographie , Embolie paradoxale/imagerie diagnostique , Communications interauriculaires/imagerie diagnostique , Amélioration d'image , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Échocardiographie transoesophagienne , Femelle , Humains , Mâle , Adulte d'âge moyen , Valeur prédictive des tests
8.
Am J Cardiol ; 84(12): 1375-80, 1999 Dec 15.
Article de Anglais | MEDLINE | ID: mdl-10606107

RÉSUMÉ

A combination of ticlopidine and aspirin has been accepted as the standard antithrombotic regimen after coronary stenting. However, ticlopidine poses serious side effects such as neutropenia or thrombocytopenia. Cilostazol, a cyclic adenosine monophosphate phosphodiesterase inhibitor, is a novel antiplatelet agent with vasodilatory properties. We compared the efficacy and safety of cilostazol plus aspirin (C+A) with ticlopidine plus aspirin (T+A) in elective coronary stenting. Three hundred patients were randomly assigned to receive C+A or T+A 2 days before stenting. The primary end point was a composite of angiographic stent thrombosis, or major cardiac events (death, myocardial infarction, bypass surgery, repeat intervention) at 30 days. The secondary end points were bleeding vascular complications, neutropenia, thrombocytopenia, or side effects requiring discontinuation of the drugs at 30 days. The primary end point was reached in 1.4% in the C+A group and 2.0% in the T+A group (p = 1.0). The rate of bleeding vascular complications was 1.4% in the C+A group and 2.0% in the T+A group (p = 1.0). The rate of drug-related side effects was not statistically different between the 2 groups but slightly higher in the T+A group than in the C+A group (2.7% vs 0.7%, p = 0.37). However, neutropenia was seen in 2 patients only in the T+A group. As a poststenting antithrombotic, C+A is as effective as T+A in preventing major cardiac events including stent thrombosis, and safer in that it does not cause neutropenia despite the fact that there is no statistical difference in the incidence of adverse effects and complications.


Sujet(s)
Angioplastie coronaire par ballonnet/instrumentation , Maladie coronarienne/thérapie , Occlusion du greffon vasculaire/prévention et contrôle , Antiagrégants plaquettaires/administration et posologie , Endoprothèses , Tétrazoles/administration et posologie , Ticlopidine/administration et posologie , Adulte , Sujet âgé , Acide acétylsalicylique/administration et posologie , Acide acétylsalicylique/effets indésirables , Cause de décès , Cilostazol , Coronarographie , Maladie coronarienne/mortalité , Association de médicaments , Femelle , Études de suivi , Occlusion du greffon vasculaire/mortalité , Humains , Mâle , Adulte d'âge moyen , Infarctus du myocarde/mortalité , Infarctus du myocarde/thérapie , Antiagrégants plaquettaires/effets indésirables , Récidive , Taux de survie , Tétrazoles/effets indésirables , Ticlopidine/effets indésirables , Résultat thérapeutique
9.
Yonsei Med J ; 40(4): 331-8, 1999 Aug.
Article de Anglais | MEDLINE | ID: mdl-10487135

RÉSUMÉ

Experiments were designed to characterize the cellular mechanisms of action of endothelium-derived vasodilator substances in the rabbit femoral artery. Acetylcholine (ACh, 10(-8)-10(-5) M) induced a concentration-dependent relaxation of isolated endothelium-intact arterial rings precontracted with norepinephrine (NE, 10(-6) M). The ACh-induced response was abolished by the removal of endothelium. NG-nitro-L-arginine (L-NAME, 10(-4) M), an inhibitor of NO synthase, partially inhibited ACh-induced endothelium-dependent relaxation, whereas indomethacin (10(-5) M) showed no effect on ACh-induced relaxation. 25 mM KCl partially inhibited ACh-induced relaxation by shifting the concentration-response curve and abolished the response when combined with L-NAME and NE. In the presence of L-NAME, ACh-induced relaxation was unaffected by glibenclamide (10(-5) M) but significantly reduced by apamin (10(-6) M), and almost completely blocked by tetraethylammonium (TEA, 10(-3) M), iberiotoxin (10(-7) M) and 4-aminopyridine (4-AP, 5 x 10(-3) M). The cytochrome P450 inhibitors, 7-ethoxyresorufin (7-ER, 10(-5) M) and miconazole (10(-5) M) also significantly inhibited ACh-induced relaxation. Ouabain (10(-6) M), an inhibitor of Na+, K(+)-ATPase, or K(+)-free solution, also significantly inhibited ACh-induced relaxation. ACh-induced relaxation was not significantly inhibited by 18-alpha-glycyrrhetinic acid (18 alpha-GA, 10(-4) M). These results of this study indicate that ACh-induced endothelium-dependent relaxation of the rabbit femoral artery occurs via a mechanism that involves activation of Na+, K(+)-ATPase and/or activation of both the voltage-gated K+ channel (Kv) and the large-conductance, Ca(2+)-activated K+ channel (BKCa). The results further suggest that EDHF released by ACh may be a cytochrome P450 product.


Sujet(s)
Facteurs biologiques/physiologie , Artère fémorale/physiologie , Canaux potassiques/physiologie , Acétylcholine/pharmacologie , Animaux , Femelle , Artère fémorale/effets des médicaments et des substances chimiques , Techniques in vitro , Mâle , Lapins , Vasodilatation/physiologie , Vasodilatateurs/pharmacologie
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