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Several Clinical Trials (several + clinical_trials)
Selected AbstractsHigh-dose glucose-insulin-potassium treatment reduces myocardial apoptosis in patients with acute myocardial infarctionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2005L. Zhang Abstract Background, Several clinical trials have suggested that a metabolic cocktail of glucose-insulin-potassium (GIK) decreases mortality rates in patients with acute myocardial infarction (AMI). It has also been reported that Fas-mediated apoptosis plays an important role in ischaemic/reperfusion injury in the rat model. This study was designed to evaluate the interaction of ischaemic/reperfusion and reperfusion therapy coadministered with high-dose GIK treatment on soluble Fas/APO-1 (sFas) and Fas ligand (sFasL) plasma concentration in patients with AMI. Materials and methods, Seventy-four patients presenting with AMI who underwent reperfusion therapy were randomized into a GIK group (n = 35) receiving high-dose GIK for 24 h or a vehicle group (n = 39). Thirty-four control subjects were also enrolled in the present study. Strepavidin-biotin ELISA was used to determine the soluble sFas and sFasL plasma concentration at baseline, 24 h (h), 3 day (d), 7 d and 14 d. Results, Soluble Fas and sFas-L serum concentrations ([sFas] and [sFas-L]) of patients with AMI were significantly elevated at baseline as compared with normal controls (NCs; P < 0·01 vs. NC). The sFas in the GIK and vehicle groups markedly decreased 24 h after the GIK infusion (10·7,5·9 ng mL,1 and 9·7,6·5 ng mL,1; P < 0·01 vs. baseline) and then increased during the 3,7-d period (5·9,12·1 ng mL,1 and 6·5,11·1 ng mL,1; P < 0·01 vs. 24 h). The GIK group demonstrated reduced sFas (12·1,5·9 ng mL,1) at 14 d (P < 0·01 vs. 7 d), with no concomitant changes in the vehicle group. The sFas-L in the GIK and vehicle groups was not significant different during the 14-d period. Conclusions, These results indicate that the sFas and sFasL in patients with AMI increased significantly compared with NC. Owing to the cardioprotective effects reported here and by others, a high-dose GIK infusion co-administered with the timely re-establishment of nutritive perfusion should be strongly considered as a treatment of choice for AMI. Additionally, sFas may be a valuable marker of the physiological response to ischaemic/reperfusion injury and reperfusion associated with high-dose GIK treatment. [source] External validation of a risk group defined by recursive partitioning analysis in patients with head and neck carcinoma treated with surgery and postoperative radiotherapyHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2007Xavier León MD Abstract Background: Several clinical trials have proved that concurrent chemoradiotherapy is more efficacious than radiotherapy alone among high-risk patients with head and neck squamous cell carcinoma (HNSCC) who undergo surgery. A risk-group classification defined according to a recursive partitioning analysis (RPA) for these patients has been recently proposed. The objective of the present study was to carry out an external validation of this RPA-derived classification system. Methods: A retrospective study of 442 HNSCC patients treated with surgery and postoperative radiotherapy was conducted. The external validity of the RPA-derived classification system was assessed, and its ability to stage patients and to predict locoregional control of the disease was compared with the TNM system. Results: The RPA-derived classification system succeeded in obtaining a monotonic prognosis gradient in locoregional control of the disease with increasing stage, and achieved greater differences in survival between stages than the TNM and pTNM classifications. Besides, the RPA method had a better homogeneity of the categories included in each stage, and in the heterogeneity between stages. Conclusions: The RPA-derived classification system allowed for the clear definition of prognostic groups in surgically treated HNSCC patients, improving the prognostic capacity of the TNM and pTNM classifications. The RPA-derived classification system is a useful tool in the definition of patients who, given a poor prognosis, should be considered candidates to adjuvant chemoradiotherapy. © 2007 Wiley Periodicals, Inc. Head Neck, 2007 [source] Off-pump, minimally invasive and robotic coronary revascularization yield improved outcomes over traditional on-pump CABGTHE INTERNATIONAL JOURNAL OF MEDICAL ROBOTICS AND COMPUTER ASSISTED SURGERY, Issue 1 2009Pavan Atluri Abstract Coronary artery disease is a global health concern, with increasing morbidity and mortality. Surgical coronary artery bypass grafting has been performed on cardiopulmonary bypass for nearly four decades, with excellent long-term durability. Beating-heart coronary surgery has been increasing in frequency in an attempt to decrease cardiopulmonary bypass-related morbidity. Furthermore, with increasing expertise and technology, minimally invasive and robotic techniques have been developed to enhance post-operative recovery, patient satisfaction and cosmesis. Several clinical trials have demonstrated decreased morbidity and more rapid recovery following off-pump, minimally invasive and robotic procedures when compared to on-pump coronary artery bypass grafts (CABGs). An equivalent extent of revascularization and medium-term anastomotic patency has been demonstrated among all approaches. Furthermore, for a large number of patients who do not have anatomy amenable to traditional coronary revascularization, adjunctive molecular therapies may provide alternative myocardial micro-revascularization. Copyright © 2008 John Wiley & Sons, Ltd. [source] Getting to goal in complex patientsCLINICAL CARDIOLOGY, Issue S2 2003C. Venkata Abstract Traditionally, the term complex hypertension has been applied to patients who have clinical evidence of target organ damage. However, this definition can be expanded to include many hypertensive patients who either present without manifest disease but harbor silent concomitant organ damage, or belong to a high-risk group and are likely to develop such damage. Thus, the number of patients who deserve special consideration as complex patients is considerable. Various factors may contribute toward classifying a patient as having complex hypertension. These include severe hypertension; concomitant conditions such as diabetes, chronic renal insufficiency, coronary artery disease, or congestive heart failure; and high-risk populations such as the elderly and African Americans. Recent evidence demonstrates that aggressive goal blood pressure (BP)-lowering therapy is the key toward halting the progression of vascular disease. Although the choice of initial therapy seems less important than achieving goal B P, the drug selected must impart efficacy, organ protection, and tolerability. Combination therapy consisting of calcium-channel blockers and angiotensin-converting enzyme inhibitors seems to achieve these desirable effects. Several clinical trials have demonstrated these agents to have favorable effects on BP and organ protection even in complex hypertension, particularly when used in combination. [source] Cardiac regeneration by progenitor cells , bedside before bench?EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2005J. Bauersachs Abstract Recent experimental and clinical trials give rise to the hope that progenitor cells could replace scar tissue after myocardial infarction with healthy functional myocardium. However, while a significant increase in left ventricular ejection fraction has been described after progenitor cell transplantation in several clinical trials, long-term results are lacking, and the mechanisms underlying the improvement of ejection fraction are unclear. Therefore, the efficacy of progenitor cell transplantation after myocardial infarction has not been established, and potential problems may have been underestimated. In-depth laboratory and animal studies are needed to determine the best cell type, optimal amount of cells, and time point for transplantation. Treatment of patients with progenitor cells outside well controlled prospective trials should be avoided. [source] Recombinant human interferon beta in relapsing,remitting multiple sclerosis: a review of the major clinical trialsEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2000M. Chofflon The beneficial effects of interferon beta (IFN-,) on disease activity in relapsing,remitting multiple sclerosis (RRMS) have been confirmed in several clinical trials. Three IFN-, products are currently available and licensed for use in RRMS at different dosages and with different routes of administration. For the prescribing physician, therefore, questions remain about the effect these differences may have on the success of therapy. This paper reviews the four large placebo-controlled clinical trials that have been conducted with IFN-, in patients with RRMS. The evidence available indicates that optimal results are likely to be achieved with the highest tolerable dosage of IFN-,. Furthermore, as inflammatory brain lesions in MS have been shown to exhibit more extensive and early axonal damage than previously suspected, early treatment may be advisable in order to delay disease progression in RRMS. [source] Use of Shade Guides for Color Measurement in Tooth-Bleaching StudiesJOURNAL OF ESTHETIC AND RESTORATIVE DENTISTRY, Issue 2003WILLIAM D. BROWNING DDS ABSTRACT Several different methods are used to measure tooth color in bleaching studies. The ADA Acceptance Program Guidelines for Home Use Tooth Whitening Products specify the use of a value-oriented shade guide and/or electronic color measurement devices. Since people perceive color differently, shade guides are a subjective measure. Differences between raters and by the same rater are well documented in the dental literature. The purposes of this article will be to discuss the advantages and disadvantages using shade guides to measure color change related to tooth whitening, and to evaluate the correlation of data gathered from the use of shade guides to electronic color measurement devices. Using an order published by the manufacturer, both the TRUBYTE® Bioform and Vita Classical guides can be arranged by value. A study by O'Brien demonstrated however, that the order is flawed and the change in brightness from tab to tab varies greatly. Despite these disadvantages, a review of data from several clinical trials demonstrates that Vita Classical shade guide data is consistent with data gathered using electronic color measurements. Furthermore, the O'Brien data can be used to make both these guides better measurement systems. The ADA Certification program standards define the degree of overall color change that should be considered clinically important. This issue is as critical as the measurement system used. Reporting color changes that are neither detectable to the human eye nor considered by the public to be important offers the profession little usable information. Given that any standard for color change during bleaching must relate to the abilities of the human eye, it is the conclusion of the author that shade guides should remain a critical element of any bleaching study. CLINICAL SIGNIFICANCE Clinicians are frequently exposed to reports of bleaching agents that have been shown to result in a change of 6, 7, 8, etc., tabs. Without understanding the limitations of the shade guide used, reports of a specific shade tab change are of little use and may actually be misleading. [source] The Costs and Quality-of-Life Outcomes of Drug-Eluting Coronary Stents: A Systematic ReviewJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 1 2007M.S., PETER W. GROENEVELD M.D. Objectives: While the efficacy of drug-eluting coronary stents (DES) has been demonstrated by several clinical trials, the impact of DES on health-care costs and recipient quality of life (QOL) is controversial. We performed a systematic review of the published literature on DES costs and the QOL effects of restenosis and target vessel revascularization (TVR). Methods: Among 536 potential articles initially identified by a broad search, 12 publications ultimately met inclusion criteria. Data were independently abstracted, evaluated for quality and relevance, and summarized by two reviewers. Excessive heterogeneity among these studies prevented formal meta-analysis, thus a narrative synthesis of the literature was performed. Results: In four economic studies, DES recipients had $1,600,$3,200 higher up-front costs than recipients of bare metal stents, but the differences in total costs after 1 year were less pronounced ($200,$1,200), and estimates of the average cost of an avoided revascularization ranged widely ($1,800,$36,900). All eight QOL studies indicated that restenosis was associated with lower QOL, but only two studies quantified this in terms of quality-adjusted life years (QALYs), with estimates ranging from 0.06 to 0.08. An additional study estimated that the median willingness to pay to prevent restenosis was $2,400,$3,600. Conclusions: There is a lack of convergence in the literature on the cost of DES in avoiding TVR. There is more agreement that the average QALY benefit of an avoided revascularization is 0.04,0.08. This implies that use of DES in patients where the average cost per avoided revascularization exceeds $8,000 may be less likely to be cost-effective. [source] Recent failures of new potential symptomatic treatments for parkinson's disease: Causes and solutionsMOVEMENT DISORDERS, Issue 7 2004Gurutz Linazasoro MD Abstract One major goal of current research in Parkinson's disease (PD) is the discovery of novel agents to improve symptomatic management. The object of these new treatments should be to provide effective symptom control throughout the course of the disease without the development of side effects such as motor and psychiatric complications. Results of several clinical trials of new treatment options reported in the past 2 years have shown negative or unsatisfactory results. Most of the drugs and surgical procedures used in these studies had been tested previously in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys as well as in the classic 6-hydroxydopamine,lesioned rat model. They raise several questions about the true reliability of animal studies, the adequacy of the working hypotheses and design of clinical trials, the validity of tools in current use to evaluate a specific effect, and the selectivity of the drugs used. All these factors may explain failure. This review focuses on pharmacological and surgical treatments tested to improve the management of patients with motor fluctuations and dyskinesias. Some of the recent trials and possible reasons for their lack of success are critically analysed. Finally, some suggestions to avoid further failures and improve results are proposed. © 2004 Movement Disorder Society [source] Hemostatic complications of angiogenesis inhibitors in cancer patients,AMERICAN JOURNAL OF HEMATOLOGY, Issue 11 2008Francesca Elice Tumor vasculature and tumor-associated neo-angiogenesis have recently become major targets for rational drug design of antineoplastic agents. Five such agents with angiogenesis inhibiting activity (thalidomide, lenalidomide, bevacizumab, sunitinib, sorafenib) have already obtained US Food and Drug Administration approval for clinical use and many others have entered clinical trials. Vascular complications, including venous or arterial thromboembolism and hemorrhage, have emerged as relevant toxicities in several clinical trials with angiogenesis inhibitors. Given the well-known interplay between the blood clotting system, angiogenesis, and tumor growth, a better understanding of the impact of these new drugs on overall hemostatic balance is required. In this brief overview, we discuss the incidence of hemostatic complications, the likely pathogenetic mechanisms involved, and the critical need to establish in randomized clinical trials the usefulness of thrombosis prophylaxis to prevent these complications. Careful documentation of hemostatic complications during treatment with each of the new antiangiogenic drugs is warranted. Further studies are urgently required to better define the causal association of these new agents with hemostatic complications and to establish the best prophylactic strategy. Am. J. Hematol., 2008. © 2008 Wiley-Liss, Inc. [source] Protein kinase C inhibition in diabetic retinopathy and microvascular diseasePRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 5 2007Dr C Walton FRCP Abstract Protein kinase C (PKC) activation by hyperglycaemia may play an important role in the evolution of diabetic retinopathy and other microvascular complications. The PKC-, inhibitor ruboxistaurin belongs to a new class of drugs and has been studied in several clinical trials in microvascular disease, the outcomes of which are described in this review. Ruboxistaurin exhibits promise as the first oral treatment shown to reduce visual loss and the need for laser treatment for macular oedema in patients with moderate to severe non-proliferative diabetic retinopathy. Copyright © 2007 John Wiley & Sons. [source] Sustained transgene expression by human cord blood derived CD34+ cells transduced with simian immunodeficiency virus agmTYO1-based vectors carrying the human coagulation factor VIII gene in NOD/SCID miceTHE JOURNAL OF GENE MEDICINE, Issue 10 2004Jiro Kikuchi Abstract Background An Erratum has been published for this article in Journal of Gene Medicine 7(6), 2005, 836. Gene therapy is being studied as the next generation therapy for hemophilia and several clinical trials have been carried out, albeit with limited success. To explore the possibility of utilizing autologous bone marrow transplantation of genetically modified hematopoietic stem cells for hemophilia gene therapy, we investigated the efficacy of genetically engineered CD34+ cell transplantation to NOD/SCID mice for expression of human factor VIII (hFVIII). Methods CD34+ cells were transduced with a simian immunodeficiency virus agmTYO1 (SIV)-based lentiviral vector carrying the enhanced green fluorescent protein (eGFP) gene (SIVeGFP) or the hFVIII gene (SIVhFVIII). CD34+ cells transduced with SIV vectors were transplanted to NOD/SCID mice. Engraftment of transduced CD34+ cells and expression of transgenes were studied. Results We could efficiently transduce CD34+ cells using the SIVeGFP vector in a dose-dependent manner, reaching a maximum (99.6 ± 0.1%) at MOI of 5 × 103 vector genome/cell. After transducing CD34+ cells with SIVhFVIII, hFVIII was produced (274.3 ± 20.1 ng) from 106 CD34+ cells during 24 h in vitro incubation. Transplantation of SIVhFVIII-transduced CD34+ cells (5,10 × 105) at a multiplicity of infection (MOI) of 50 vector genome/cell into NOD/SCID mice resulted in successful engraftment of CD34+ cells and production of hFVIII (minimum 1.2 ± 0.9 ng/mL, maximum 3.6 ± 0.8 ng/mL) for at least 60 days in vivo. Transcripts of the hFVIII gene and the hFVIII antigen were also detected in the murine bone marrow cells. Conclusions Transplantation of ex vivo transduced hematopoietic stem cells by non-pathogenic SIVhFVIII without exposure of subjects to viral vectors is safe and potentially applicable for gene therapy of hemophilia A patients. Copyright © 2004 John Wiley & Sons, Ltd. [source] Gene therapy for HIV/AIDS: the potential for a new therapeutic regimenTHE JOURNAL OF GENE MEDICINE, Issue 8 2003Greg Fanning Abstract Human Immunodeficiency Virus (HIV) is the etiologic agent of Acquired Immunodeficiency Syndrome (AIDS). HIV/AIDS is a disease that, compared with the not so distant past, is now better held in check by current antiretroviral drugs. However, it remains a disease not solved. Highly active antiretroviral therapy (HAART) generally uses two non-nucleoside and one nucleoside reverse transcriptase (RT) inhibitor or two non-nucleoside RT and one protease inhibitor. HAART is far more effective than the mono- or duo-therapy of the past, which used compounds like the nucleoside reverse transcriptase inhibitor AZT or two nucleoside reverse transcriptase inhibitors. However, even with the relatively potent drug cocktails that comprise HAART, there are the issues of (i) HIV escape mutants, (ii) an apparent need to take the drugs in an ongoing manner, and (iii) the drugs' side effects that are often severe. This review speaks to the potential addition to these potent regimens of another regimen, namely the genetic modification of target hematopoietic cells. Such a new treatment paradigm is conceptually attractive as it may yield the constant intracellular expression of an anti-HIV gene that acts to inhibit HIV replication and pathogenicity. A body of preclinical work exists showing the inhibition of HIV replication and decreased HIV pathogenicity by anti-HIV genetic agents. This preclinical work used hematopoietic cell lines and primary cells as the target tissue. More recently, several clinical trials have sought to test this concept in vivo. Copyright © 2003 John Wiley & Sons, Ltd. [source] Pathogenic CD8+ T cells in multiple sclerosis,ANNALS OF NEUROLOGY, Issue 2 2009Manuel A. Friese MD Traditionally, autoimmune pathogeneses have been attributed to CD4+ T lymphocytes, as in multiple sclerosis (MS), rheumatoid arthritis, type 1 diabetes mellitus, and/or to B lymphocytes, as in myasthenia gravis and systemic lupus erythematosus. That is because their primary genetic associations are mostly with certain human leukocyte antigen class II alleles, whose gene products present antigens to CD4+ T cells. Because few autoimmune diseases show stronger associations with major histocompatibility complex class I alleles (ankylosing spondylitis, Behçet's disease, and psoriasis), CD8+ T cells, which interact with major histocompatibility complex class I molecules, have been largely ignored in autoimmunity research. However, a variety of findings has recently revived interest in this population, particularly in MS. First, it shows associations with major histocompatibility complex class I alleles. Second, its lesions show a predominance of CD8+ T cells. Third, these represent effectors that can directly damage central nervous system target cells. Furthermore, several clinical trials of monoclonal antibodies specifically against CD4+ T cells, or the polarizing cytokines on which they depend, have failed to show any therapeutic benefit in MS, unlike broader-spectrum antibodies that deplete all T cells. Here, we review the evidence that CD8+ T cells play a role in MS pathogenesis. Ann Neurol 2009;66:132,141 [source] Salbutamol for hyperkalaemia in childrenACTA PAEDIATRICA, Issue 11 2001E Helfrich Hyperkalaemia is a potentially fatal disorder that demands direct treatment. The efficacy of traditional medical treatment is unpredictable, limited, of short duration or carries the risk of serious adverse events. The administration of salbutamol for hyperkalaemia in children is described in several clinical trials and case reports. Conclusion: Salbutamol, inhaled or infused, is safe and efficacious and results in a predictable and long-lasting reduction in serum potassium. Salbutamol merits a place as the preferred medication for hyperkalaemia in children without arrhythmias. If follow-up with haemodialysis is required, the administration of salbutamol gives time to make the necessary preparations. [source] | ||||||||||||||||||||||