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Terms modified by Recent Clinical Selected AbstractsMR imaging in assessing cardiovascular interventions and myocardial injuryCONTRAST MEDIA & MOLECULAR IMAGING, Issue 1 2007Alexis Jacquier Abstract Performing an MR-guided endovascular intervention requires (1) real-time tracking and guidance of catheters/guide wires to the target, (2) high-resolution images of the target and its surroundings in order to define the extent of the target, (3) performing a therapeutic procedure (delivery of stent or injection of gene or cells) and (4) evaluating the outcome of the therapeutic procedure. The combination of X-ray and MR imaging (XMR) in a single suite was designed for new interventional procedures. MR contrast media can be used to delineate myocardial infarcts and microvascular obstruction, thereby defining the target for local delivery of therapeutic agents under MR-guidance. Iron particles, or gadolinium- or dysprosium-chelates are mixed with the soluble injectates or stem cells in order to track intramyocardial delivery and distribution. Preliminary results show that genes encoded for vascular endothelial and fibroblast growth factor and cells are effective in promoting angiogenesis, arteriogenesis, perfusion and LV function. Angiogenic growth factors, genes and cells administered under MR-guided minimally invasive catheter-based procedures will open up new avenues in treating end-stage ischemic heart disease. The optimum dose of the therapeutic agents, delivery devices and real-time imaging techniques to guide the delivery are currently the subject of ongoing research. The aim of this review is to (1) provide an updated review of experiences using MR imaging to guide transcatheter therapy, (2) address the potential of cardiovascular magnetic resonance (MR) imaging and MR contrast media in assessing myocardial injury at a molecular level and labeling cells and (3) illustrate the applicability of the non-invasive MR imaging in the field of angiogenic therapies through recent clinical and experimental publications. Copyright © 2007 John Wiley & Sons, Ltd. [source] FLT3 Antibody-based therapy for leukemiaDRUG DEVELOPMENT RESEARCH, Issue 6 2006Yiwen Li Abstract Technological advances in antibody generation and production have facilitated recent clinical and commercial success with antibody-based cancer therapeutics. The class III receptor tyrosine kinase FLT3 is highly expressed on the blast cells in most cases of acute myelogenous leukemia (AML) and B-cell acute lymphoblastic leukemia (ALL). Activating mutations of FLT3 are detected in approximately 37% AML patients. FLT3 expression in normal tissue is limited to myeloid and B-cell precursor cells. Therefore, over-expressed or mutated FLT3 is an attractive target for therapeutic intervention using monoclonal antibodies. This review will discuss recent progress in the development of anti-FLT3 antibodies as well as their therapeutic potentials in the treatment of AML and other hematological malignancies. Drug Dev. Res. 67:495,500, 2006. © 2006 Wiley-Liss, Inc. [source] Epidermal growth factor receptor in relation to tumor development: EGFR-targeted anticancer therapyFEBS JOURNAL, Issue 2 2010Isamu Okamoto The discovery that signaling by the epidermal growth factor receptor (EGFR) plays a key role in tumorigenesis prompted efforts to target this receptor in anticancer therapy. Two different types of EGFR-targeted therapeutic agents were subsequently developed: mAbs, such as cetuximab and panitumumab, which target the extracellular domain of the receptor, thereby inhibiting ligand-dependent EGFR signal transduction; and small-molecule tyrosine kinase inhibitors, such as gefitinib and erlotinib, which target the intracellular tyrosine kinase domain of the EGFR. Furthermore, recent clinical and laboratory studies have identified molecular markers that have the potential to improve the clinical effectiveness of EGFR-targeted therapies. This minireview summarizes the emerging role of molecular profiling in guiding the clinical use of anti-EGFR therapeutic agents. [source] Factors affecting carbon dioxide laser treatment for oral precancer: A patient cohort studyLASERS IN SURGERY AND MEDICINE, Issue 1 2009O. Hamadah DDS Abstract Background Although the benefits of CO2 laser surgery in oral precancer management have been evaluated, little consideration has been given to the factors which may influence treatment outcome, especially amongst patients developing recurrence or malignant transformation. Study Design Seventy eight patients (51 males, 27 females; mean age 57.8 years) undergoing CO2 laser excision of single, new dysplastic oral precancer lesions (OPLs) were followed up for a minimum of 2 years and the influence of clinico-pathological parameters, socio-demographic factors and the presence or absence of residual dysplasia in excision margins upon clinical outcome were examined. Results Seventy three percent of patients were smokers and 78% consumed alcohol regularly. The majority of lesions were leukoplakias arising in the floor of mouth and ventro-lateral tongue and moderate or severe dysplasia accounted for 86% of histopathological diagnoses. Patient follow up ranged from 24 to 119 months (mean 58 months). Sixty four percent of patients were disease free at most recent clinical follow up, whilst 32% developed local recurrent dysplasia or new site dysplasia with 4% developing oral squamous cell carcinoma (but at sites distinct from their initial OPL). Excision margins were clear in 55% of cases, but 19% showed mild, 21% moderate and 5% severe dysplasia on histopathological examination. No statistically significant associations were seen between patients' age, gender, lesion appearance, site of origin, histopathological grading, presence of dysplasia in resection margins, or alcohol consumption and clinical outcome. Smokers, however, were at significantly higher risk of dysplasia recurrence compared to ex-smokers or non-smokers (P,=,0.04). Conclusions In the absence of agreed treatment protocols for OPLs, we recommend CO2 laser surgery as an effective treatment modality offering precise lesion excision, full histopathological assessment, minimal post-operative morbidity and a 64% disease free clinical outcome. Regular patient follow up is encouraged due to the persistence of field cancerisation effects. Lasers Surg. Med. 41:17,25, 2009. © 2008 Wiley-Liss, Inc. [source] A critical review of the cannabinoid receptor as a drug target for obesity managementOBESITY REVIEWS, Issue 1 2009F. Akbas Summary The discovery of cannabinoids, with the well-known stimulatory effect of Cannabis sativa on appetite, has offered a new drug target for obesity treatment. Cannabinoids act on two different receptors: CB1 receptors which are sited in the brain and many peripheral tissues, and CB2 receptors which are primarily found in immune system cells. Cannabinoid receptor antagonists act centrally by blocking CB1 receptors, thereby reducing food intake. Moreover, they probably also act peripherally by increasing thermogenesis and therefore energy expenditure, as has been suggested by animal experiments. Despite these promising mechanisms of action, recent clinical studies examining the effect of the two CB1 receptor antagonists rimonabant and taranabant showed that the attained weight loss did not exceed that attained with other currently approved anti-obesity medications. Moreover, potentially severe psychiatric adverse effects limit their clinical use. As several new CB1 receptor antagonists are presently undergoing development, it remains to be elucidated to what extent they differ in terms of efficacy and safety. This review primarily discusses how close cannabinoid receptor antagonists are to the ideal anti-obesity drug, with respect to their mechanisms of action, clinical effectiveness and safety. [source] Annotation: Childhood-onset schizophrenia: clinical and treatment issuesTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 2 2004Joan Rosenbaum Asarnow Background:, In the past 10 years, there has been increased research on childhood-onset schizophrenia and clear advances have been achieved. Method:, This annotation reviews the recent clinical and treatment literature on childhood-onset schizophrenia. Results:, There is now strong evidence that the syndrome of childhood-onset schizophrenia exists and there are several similarities between childhood- and later-onset schizophrenia. Schizophrenia in youth can be reliably diagnosed using the same criteria employed with adults, and childhood-onset schizophrenia is predictive of schizophrenia or schizophrenia spectrum disorders in adulthood. Data is accumulating to guide pharmacological treatment strategies, and practice parameters have been developed to guide clinical care. Conclusions:, Despite significant advances, there remains an urgent need for additional research on treatment and service delivery strategies. Promising work with adults highlights the importance of attending to psychosocial as well as pharmacologic treatment strategies, and the potential value of preventive interventions. [source] IS THERE STILL A ROLE FOR THE CLASSICAL COX-MAZE III?ANZ JOURNAL OF SURGERY, Issue 5 2006Cheng-Hon Yap Background: The incidence of surgery for atrial fibrillation (AF) is rising, paralleled by an increase in the types of lesion sets and energy sources used. These alternate energy sources have simplified the surgery at the expense of increased cost of consumables. The classical Cox-Maze III is the gold standard therapy with a proven efficacy in curing AF. Our complete experience with this procedure is presented. Methods: All 28 patients undergoing the classical Cox-Maze III procedure at our institution underwent preoperative assessment and were followed prospectively. Results: Twenty-eight patients underwent the Cox-Maze III procedure between January 2001 and May 2003. Their mean age was 65 years (range, 44,80 years). Twenty-five patients had concomitant cardiac procedures. Mean duration of AF was 8.3 years. Permanent AF was present in 82%. Mean follow-up time was 15 ± 8 months (range, 4,30 months). There were no perioperative or late deaths, or thromboembolic events. Sixty-one per cent had early (<3 months) atrial arrhythmia. Freedom from AF at most recent clinical follow up was 93%. Freedom from late atrial arrhythmia was 82%. Freedom from late AF or atrial flutter by pacemaker interrogation or Holter assessment was 77%. Anti-arrhythmic medication use was reduced. New York Heart Association class improved from an average of 2.8 preoperatively to 1.3 postoperatively. Conclusion: The result of the present study shows the safety and efficacy of the classical Cox-Maze III procedure. With the advantage of proven long-term efficacy, demonstrable safety and avoidance of costly technology, the Cox-Maze III should not be discounted as a treatment option in patients because of its perceived complexity. [source] Sentinel lymph node as a target of molecular diagnosis of lymphatic micrometastasis and local immunoresponse to malignant cellsCANCER SCIENCE, Issue 3 2008Hiroya Takeuchi The sentinel lymph node (SLN) is defined as the lymph node(s) first receiving lymphatic drainage from the site of the primary tumor. The histopathological status of SLN is one of the most significant predictors of recurrence and overall survival for most clinical stage I/II solid tumors. Recent progress in molecular techniques has demonstrated the presence of micrometastatic tumor cells in SLN. There is now a growing body of data to support the clinical relevance of SLN micrometastasis in a variety of solid tumors. Increasing the sensitivity of occult tumor cell detection in the SLN, using molecular-based analysis, should enable a more accurate understanding of the clinical significance of various patterns of micrometastatic nodal disease. The establishment of metastasis to SLN might not be simply reflected by the flow dynamics of lymphatic fluid that drains from the primary site to the SLN, and the transportation of viable cancer cells. Recent studies have demonstrated that primary tumors can actively induce lymphangiogenesis and promote SLN metastasis. Moreover chemokine receptors in tumor cells may facilitate organ-specific tumor metastasis in many human cancers and some experimental models. In contrast, recent clinical and preclinical studies regard SLN as the first lymphoid organ to respond to tumor antigenic stimulation. SLN dramatically show morphological, phenotypical and functional changes that indicate immune suppression by tumor cells. The immune suppression in SLN results in failure of prevention or eradication of tumor metastasis. The mechanism of immunomodulation remains unclear; however, several regulatory molecules produced by tumor cells and tumor-associated macrophages or lymphocytes are likely to be responsible for inducing the immune suppression in SLN. Further studies may develop a novel immunotherapy that overcomes tumor-induced immune suppression and can prevent or eradicate SLN metastasis. (Cancer Sci 2008; 99: 441,450) [source] Modern therapeutic strategies for paediatric systemic lupus erythematosus and lupus nephritisACTA PAEDIATRICA, Issue 7 2010Stephen D Marks Abstract There is still a significant morbidity and mortality associated with childhood-onset systemic lupus erythematosus (SLE), despite an increasing armamentarium of immunosuppressive agents. The ideal therapeutic strategy for children and adolescents with SLE should provide the right amount of treatment to allow normal growth, development and fertility while reducing the disease activity and damage that can be accrued over the years. Each patient should have individualized treatments tailored to their organ involvement, disease severity and history of flares together with recent clinical, haematological and immunological parameters to avoid further flares of disease activity and side-effects of treatment, especially severe infections and future malignancies. The most commonly cited side-effects of medications include Cushingoid features of corticosteroids, infective complications of cyclophosphamide and gastrointestinal side-effects of mycophenolate mofetil. There is increasing evidence to support the use of oral mycophenolate mofetil as opposed to cyclophosphamide for both induction and maintenance therapies in many children with SLE with or without lupus nephritis (LN). Recently, case series utilizing B-lymphocyte depletion therapies with rituximab look promising for patients with severe or refractory disease activity. In this article, we explore current evidence to effectively treat children and adolescents with SLE with or without LN. Conclusion:, Modern therapeutic strategies include reduced doses and use of corticosteroids and intravenous cyclophosphamide respectively, with increased use of azathioprine, MMF and rituximab. [source] Immunostimulatory cellular responses of cured Leishmania -infected patients and hamsters against the integral membrane proteins and non-membranous soluble proteins of a recent clinical isolate of Leishmania donovaniCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2005R. Garg Summary Development of an effective immunoprophylactic agent for visceral leishmaniasis (VL) has become imperative due to the increasing number of cases of drug resistance and relapse. Live and killed whole parasites as well as fractionated and recombinant preparations have been evaluated for vaccine potential. However, a successful vaccine against the disease has been elusive. Because protective immunity in human and experimental leishmaniasis is predominantly of the Th1 type, immunogens with Th1 stimulatory potential would make good vaccine candidates. In the present study, the integral membrane proteins (IMPs) and non-membranous soluble proteins (NSPs), purified from promastigotes of a recent field isolate, Leishmania donovani stain 2001, were evaluated for their ability to induce cellular responses in cured patients (n = 9), endemic controls (n = 5) of visceral leishmaniasis (VL) and treated hamsters (n = 10). IMPs and NSPs induced significant proliferative responses (SI 6·3 ± 4·1 and 5·6 ± 2·3, respectively; P < 0·01) and IFN-, production (356·3 ± 213·4 and 294·29 ± 107·6 pg/ml, respectively) in lymphocytes isolated from cured VL patients. Significant lymphoproliferative responses against IMPs and NSPs were also noticed in cured Leishmania animals (SI 7·2 ± 4·7 & 6·4 ± 4·1, respectively; P < 0·01). In addition, significant NO production in response both IMPs and NSPs was also noticed in macrophages of hamsters and different cell lines (J774A-1 and THP1). These results suggest that protective, immunostimulatory molecules are present in the IMP and NSP fractions, which may be exploited for development of a subunit vaccine for VL. [source] Commercial broth microdilution panel validation and reproducibility trials for NVP PDF-713 (LBM 415), a novel inhibitor of bacterial peptide deformylaseCLINICAL MICROBIOLOGY AND INFECTION, Issue 9 2004T. R. Fritsche Abstract NVP PDF-713 (LBM 415) is a peptide deformylase inhibitor being progressed into clinical trials. Dry-form broth microdilution panels of NVP PDF-713 were compared to reference MIC panels of 552 recent clinical isolates. Most (99.2%) dry-form MIC results were within ± 1 log2 dilution of the reference panel MICs. Of the bacteria tested, Streptococcus pneumoniae and Haemophilus influenzae showed a bias towards higher and lower MICs, respectively. Same-day and between-day reproducibility tests showed that 98.9% and 96.7% of MIC values, respectively, were within ± 1 log2 dilution step, thereby demonstrating a high degree of reliability of the dry-form MIC product for clinical studies. [source] |