Home About us Contact
|
Home About us Contact | ||
|
|
||
Significant Therapeutic Effect (significant + therapeutic_effect)
Selected AbstractsA randomized, placebo-controlled trial of paroxetine in nursing home residents with non-major depressionDEPRESSION AND ANXIETY, Issue 3 2002Adam B. Burrows M.D. Abstract Depression is common across a broad spectrum of severity among nursing home residents. Previous research has demonstrated the effectiveness of antidepressants in nursing home residents with major depression, but it is not known whether antidepressants are helpful in residents with less severe forms of depression. We conducted a randomized double-blind placebo-controlled 8-week trial comparing paroxetine and placebo in very old nursing home residents with non-major depression. The main outcome measure was the primary nurse's Clinical Impression of Change (CGI-C). Additional outcome measures were improvement on the interview-derived Hamilton Depression Rating Scale (HDRS) and Cornell Scale for Depression (CS) scores. Twenty-four subjects with a mean age of 87.9 were enrolled and twenty subjects completed the trial. Placebo response was high, and when all subjects were considered, there were no differences in improvement between the paroxetine and placebo groups. Two subjects that received paroxetine developed delirium, and subjects that received paroxetine were more likely to experience a decrease in Mini Mental State Exam scores (P = .03). There were no differences in serum anticholinergic activity between groups. In a subgroup analysis of 15 subjects with higher baseline HDRS and CS scores, there was a trend toward greater improvement in the paroxetine group in an outcome measure that combined the CGI-C and interview-based measures (P = .06). Paroxetine is not clearly superior to placebo in this small study of very old nursing home residents with non-major depression, and there is a risk of adverse cognitive effects. Because of the high placebo response and the trend towards improvement in the more severely ill patients, it is possible that a larger study would have demonstrated a significant therapeutic effect for paroxetine as compared with placebo. The study also illustrates the discordance between patient and caregiver ratings, and the difficulties in studying very elderly patients with mood disorders. Depression and Anxiety 15:102,110, 2002. © 2002 Wiley-Liss, Inc. [source] Selective occlusion of tumor blood vessels by targeted delivery of an antibody-photosensitizer conjugateINTERNATIONAL JOURNAL OF CANCER, Issue 7 2006Monica Fabbrini Abstract The irregular vasculature and high interstitial pressure of solid tumors hinder the delivery of cytotoxic agents to cancer cells. As a consequence, the doses of chemotherapy necessary to achieve complete tumor eradication are associated with unacceptably high toxicities. The selective thrombosis of tumor blood vessels has been postulated as an alternative avenue for combating cancer, depriving tumors of nutrients and oxygen and causing an avalanche of tumor cell deaths. The human antibody L19, specific to the EDB domain of fibronectin, a marker of angiogenesis, is capable of selective in vivo localization around tumor blood vessels and is thus a suitable agent for delivering toxic payloads to the tumor neovasculature. Here we show that a chemical conjugate of the L19 antibody with the photosensitizer bis(triethanolamine)Sn(IV) chlorin e6, after intravenous injection and irradiation with red light, caused an arrest of tumor growth in mice with subcutaneous tumors. By contrast, a photosensitizer conjugate obtained with an antibody of identical pharmacokinetic properties but irrelevant specificity did not exhibit a significant therapeutic effect. These results confirm that vascular targeting strategies, aimed at the selective occlusion/disruption of tumor blood vessels, have a significant anticancer therapeutic potential and encourage the use of antibody-photosensitizer conjugates for the therapy of superficial tumors and possibly other angiogenesis-related pathologies. © 2005 Wiley-Liss, Inc. [source] Interferon gamma (IFN-,) may reverse oral submucous fibrosisJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2001M. F. Haque Abstract: Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity and oropharyngx characterised by fibrosis in the submucosa leading to progressive limitation of the mouth opening. Interferon gamma (IFN-,) is a known anti-fibrotic cytokine. In this study we have investigated: a) the effect of IFN-, on collagen synthesis by arecoline-stimulated OSF fibroblasts in vitro (n=5), b) the effect of intra-lesional IFN-, on the fibrosis of OSF patients (n=29) and c) the immunohistochemical analysis of pre- and post-treatment inflammatory cell infiltrates and cytokine levels in the lesional tissue (n=29). The results show that the increased collagen synthesis in vitro in response to arecoline was inhibited in the presence of IFN-, (0.01,10.0 U/ml) in a dose-related way. In an open uncontrolled study intra-lesional IFN-, treatment showed improvement in the patients mouth opening from an inter-incisal distance before treatment of 21±7 mm, to 30±7 mm immediately after treatment and 30±8 mm 6-months later, giving a net gain of 8±4 mm (42%) (range 4,15 mm). Patients also reported reduced burning dysaesthesia and increased suppleness of the buccal mucosa. The post-treatment immunohistochemistry showed a decreased amount of inflammatory cell infiltrate and an altered level of cytokines compared with the pre-treatment lesional tissue. The effect of IFN-, on collagen synthesis appears to be a key to the treatment of these patients, and intra-lesional injections of the cytokine may have a significant therapeutic effect on OSF. [source] Synergistic neuroprotective effect via simian lentiviral vector-mediated simultaneous gene transfer of human pigment epithelium-derived factor and human fibroblast growth factor-2 in rodent models of retinitis pigmentosaTHE JOURNAL OF GENE MEDICINE, Issue 12 2008Masanori Miyazaki Abstract Background We previously demonstrated that a new lentiviral vector derived from nonpathogenic simian immunodeficiency virus (SIVagm) was efficient and safe for long-lasting retinal gene transfer, and that it provided the significant therapeutic effect of expressing human pigment epithelium-derived factor (hPEDF) in Royal College of Surgeons (RCS) rats. In the present study, to obtain a more pronounced outcome, we assessed the potential synergistic effect of the simultaneous gene transfer of hPEDF and human fibroblast growth factor-2 (hFGF-2) by improved third-generation SIV on RCS rats and retinal degeneration slow (rds) mice, because the former targets the primary neurons, including photoreceptor cells (PCs), whereas the latter is effective for targeting secondary neural cells, including Muller cells. Methods Vector solution (SIV-hPEDF, SIV-hFGF-2, a 1 : 1 mixture of SIV-hPEDF and SIV-hFGF-2, or SIV-enhanced green fluorescent protein) was injected into the peripheral subretinal space of 3-week-old RCS rats or rds mice. Histopathological and electroretinographic assessments were made at several points after gene transfer. Results Administration of SIV-hPEDF or SIV-hFGF-2 significantly delayed the histological PC degeneration and electrical deficit in RCS rats, and these delays were synergistically and significantly pronounced by SIV-hPEDF + SIV-hFGF-2 (1 : 1 mixture). In rds mice, functional therapeutic effects were observed even by SIV-PEDF, or SIV-FGF-2 alone and, moreover, both SIV-PEDF and SIV-FGF-2 showed higher therapeutic effects. Conclusions These synergistic rescues of retinitis pigmentosa (RP) model animals are the ,proof concept' that the ,dual' expression of hPEDF and hFGF-2 dramatically improved therapeutic efficacy by keeping lower titers. This strategy may contribute to safer and more effective gene therapy for RP. Copyright © 2008 John Wiley & Sons, Ltd. [source] Optimal prophylactic dosage and disposition of micafungin in living donor liver recipientsCLINICAL TRANSPLANTATION, Issue 6 2004Satoshi Kishino Abstract:, Micafungin, a new candin antifungal drug, has a good safety profile and a significant therapeutic effect against Candida and Aspergillus. Little is known, however, about the optimal prophylactic dosage and the disposition of micafungin in liver transplant recipients, or about the effect of continuous venovenous hemodialysis (CVVH) on the pharmacokinetics of micafungin. Six living donor liver transplant patients were enrolled in this study. The mean Cmax and Cmin (trough) values of micafungin in plasma were 6.31 ± 1.08 and 1.65 ± 0.54 ,g/mL, respectively. The mean elimination half-life (t1/2) and mean area under the curve up to 12 h post-dosing (AUC 0,12 h) were 13.63 ± 2.77 h and 50.04 ± 6.48 ,g·h/mL, respectively. The concentrations of micafungin at the inlet and outlet of the dialyzer were very similar. The mean (±SD) ratio of micafungin concentrations at the inlet and outlet of the dialyzer (coutlet/cinlet) and the clearance of micafungin were 0.96 ± 0.04 and 0.054 ± 0.04 mL/min/kg, respectively. The amount in the ultrafiltrate was 1.0 mg. Micafungin effectively prevents systemic fungal infection in patients who have undergone liver transplantation. No significant differences were observed in the disposition of micafungin in recipients, and the therapeutic drug level can be achieved by administration of micafungin at a dosage of 40,50 mg/d. The CVVH had little effect on micafungin kinetics, and no dose adjustment or modification of dosing interval was needed during CVVH. [source] | ||||||||||