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Improved Efficacy (improved + efficacy)
Selected AbstractsA Pilot Study of a Low-Tilt Biphasic Waveform for Transvenous Cardioversion of Atrial Fibrillation: Improved Efficacy Compared with Conventional Capacitor-Based Waveforms in PatientsPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 8 2008BENEDICT M. GLOVER M.D. Background:The optimal waveform tilt for defibrillation is not known. Most modern defibrillators used for the cardioversion of atrial fibrillation (AF) employ high-tilt, capacitor-based biphasic waveforms. Methods:We have developed a low-tilt biphasic waveform for defibrillation. This low-tilt waveform was compared with a conventional waveform of equivalent duration and voltage in patients with AF. Patients with persistent AF or AF induced during a routine electrophysiology study (EPS) were randomized to receive either the low-tilt waveform or a conventional waveform. Defibrillation electrodes were positioned in the right atrial appendage and distal coronary sinus. Phase 1 peak voltage was increased in a stepwise progression from 50 V to 300V. Shock success was defined as return of sinus rhythm for ,30 seconds. Results:The low-tilt waveform produced successful termination of persistent AF at a mean voltage of 223 V (8.2 J) versus 270 V (6.7 J) with the conventional waveform (P = 0.002 for voltage, P = ns for energy). In patients with induced AF the mean voltage for the low-tilt waveform was 91V (1.6 J) and for the conventional waveform was 158 V (2.0 J) (P = 0.005 for voltage, P = ns for energy). The waveform was much more successful at very low voltages (less than or equal to 100 V) compared with the conventional waveform (Novel: 82% vs Conventional 22%, P = 0.008). Conclusion:The low-tilt biphasic waveform was more successful for the internal cardioversion of both persistent and induced AF in patients (in terms of leading edge voltage). [source] Improved efficacy and tolerability of retinoic acid in acne vulgaris: a new topical formulation with cyclodextrin complex ,JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2004RY Anadolu ABSTRACT Objectives, Retinoic acid (RA) has long been used, both topically and systemically, for disorders of keratinization, acne and related disorders. In the present study, the efficacy and tolerability of topical RA prepared as a cyclodextrin beta complex (,-CD) is investigated in 66 acne vulgaris patients. Methods, This randomized, double-blind, placebo-controlled study compares nightly topical application of RA/,-CD complex hydrogel formulation (0.025%), RA/,-CD complex in moisturizing base (0.025%), hydrogel base, moisturizer base or a commercial RA gel (0.05%) in acne vulgaris patients. Improvement of acne was assessed using a 5-point improvement scale and by measuring sebum and moisture content of the skin using an SM 810 sebumeter/corneometer. Results, After 3 months of treatment, mean scores of acne improvement on the 5-point scale were 4 with the RA/,-CD complex hydrogel formulation, 4.1 with the RA/,-CD complex in moisturizing base, 1.2 with hydrogel placebo base, 1.1 with moisturizer placebo base and 3 with the commercial RA product. All patients treated with the commercial product experienced local side-effects. One patient discontinued due to severe irritation. None of the patients treated with the RA/,-CD complex in the moisturizing base and hydrogel formulation experienced significant local irritation, although the sebum content of the skin decreased after application of the RA/,-CD preparations. This change was not significant compared to controls. The moisture content of the skin was better preserved in the group treated with the RA/,-CD complex in the moisturizing base. Conclusion, The topical RA/,-CD complex, in hydrogel and moisturizing base, was more effective than the twice concentrated commercial RA product. There were few topical side-effects with this new formulation, which increases patient compliance. Topical RA/,-CD (0.025% RA) did not significantly reduce sebum secretion but may help to preserve optimum epidermal moisture content with the proper base formulation. This is the first study in the literature reporting efficacy and tolerability of the topical RA/,-CD complex in acne vulgaris. We conclude that the topical RA/,-CD complex displays an improved efficacy and tolerability profile and is an effective treatment alternative for acne vulgaris. [source] Anticonvulsant Efficacy of Topiramate in Phenytoin-Resistant Kindled RatsEPILEPSIA, Issue 4 2000Elke Reissmüller Summary: Purpose: We evaluated the anticonvulsant efficacy of topiramate (TPM), a structurally novel antiepileptic drug (AED), in amygdala kindled rats that had been preselected with respect to their response to phenytoin (PHT). Methods: Anticonvulsant response was tested by determining the afterdischarge threshold (ADT;i.e., a sensitive measure for drug effects on focal seizure activity). By repeated testing with the PHT prodrug fosphenytoin (FOS) three groups of kindled rats were separated: rats in which consistent anticonvulsant effects were obtained (PHT responders), rats that showed no anticonvulsant response (PHT nonresponders), and rats with variable responses (variable PHT responders). The latter, largest group was used to evaluate at which doses and pretreatment times TPM exerted significant anticonvulsant effects on ADT. For this purpose, TPM was tested at four doses (20, 40, 80, 160 mg/kg i.p.) and two pretreatment times (1 and 4 h). The most effective treatment protocol was then used for TPM testing in PHT responders and nonresponders. Results: TPM proved to be an effective AED in the kindling model. At 40 mg/kg, significant ADT increases were obtained after both 1 and 4 h after administration. In addition to the effect on focal seizure threshold, seizure severity and duration recorded at ADT were decreased by TPM, indicating that this drug acts on both seizure threshold and seizure spread. In PHT nonresponders, TPM significantly increased ADT, which is in line with its proven efficacy in patients with refractory partial epilepsy in whom phenytoin has failed. However, TPM was more efficacious in increasing ADT in PHT responders than in nonresponders, substantiating that the difference between these groups of kindled rats extends to other AEDs. Repeated testing of kindled rats with TPM indicated that, similar to PHT, there are individual kindled rats without anticonvulsant response to TPM (i.e., TPM nonresponders). Conclusions: The data of this study substantiate that PHT nonresponders are a unique model for the search of new AEDs with improved efficacy in refractory partial epilepsy. [source] Effect of pulsed ultrasound in combination with gentamicin on bacterial viability in biofilms on bone cements in vivoJOURNAL OF APPLIED MICROBIOLOGY, Issue 3 2005G.T. Ensing Abstract Aims:, The aim of this study is to investigate whether pulsed ultrasound (US) in combination with gentamicin yields a decreased viability of bacteria in biofilms on bone cements in vivo. Methods and Results:, Bacterial survival on bone cement in the presence and absence of ultrasound was compared in a rabbit model. Two bone cement samples with an Escherichia coli ATCC 10798 biofilm were implanted in a total of nine rabbits. In two groups bone cement discs loaded with gentamicin, freshly prepared and aged were used, and in one group unloaded bone cement discs in combination with systemically administered gentamicin. Pulsed ultrasound with a frequency of 28·48 kHz and a maximum acoustic intensity of 500 mW cm,2 was applied continuously from 24 h till 72 h postsurgery on one of the two implanted discs. After euthanization and removal of the bacteria from the discs, the number of viable bacteria were quantified and skin samples were analysed for histopathological examination. Application of ultrasound, combined with gentamicin, reduced the viability of the biofilms in all three groups varying between 58 and 69% compared with the negative control. Histopathological examinations showed no skin lesions. Conclusions:, Ultrasound resulted in a tendency of improved efficacy of gentamicin, either applied locally or systemically. Usage of ultrasound in this model proved to be safe. Significance and Impact of the Study:, This study implies that ultrasound could improve the prevention of infection immediately after surgery, especially because the biomaterials, gentamicin and ultrasound used in this model are all in clinical usage, but not yet combined in clinical practice. [source] Specificities of proteases for use in leather manufactureJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 3 2006Farhad Foroughi Abstract Proteases are used in leather manufacture in the processes of soaking, unhairing and bating of hides and skins. However proteases can be relatively non-specific in their usage, and for improved efficacy of enzyme biocatalysis within the industry, an analysis of specific activities of enzymes towards skin proteins was undertaken. Most commercial proteases for soaking showed substantial activity against the substrates elastin,Congo Red and Azocoll but little or no activity against keratin,azure and hide powder black. Enzymes used for unhairing in conjunction with 30% of the usual concentration of sulfide to effect chemical unhairing showed moderate activity against all substrates tested (selected as representative of skin proteins), while proteases used in bating showed activity against Azocoll and elastin,Congo Red but had no keratinase activity and little activity against hide powder black. Bating proteases and soaking proteases displayed similar activities at pH 8. Microbes isolated in the screening of organisms from putrefied skins included one fungal and two bacterial isolates whose extracellular enzymes had efficient unhairing activity without the addition of sulfide. Enzyme activities for these proteases included high activity measured against Azocoll with little or no activity against elastin,Congo Red, keratin,azure and hide powder black. Neither elastase nor keratinase activities were determined as being essential for unhairing. Copyright © 2005 Society of Chemical Industry [source] Improved efficacy and tolerability of retinoic acid in acne vulgaris: a new topical formulation with cyclodextrin complex ,JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2004RY Anadolu ABSTRACT Objectives, Retinoic acid (RA) has long been used, both topically and systemically, for disorders of keratinization, acne and related disorders. In the present study, the efficacy and tolerability of topical RA prepared as a cyclodextrin beta complex (,-CD) is investigated in 66 acne vulgaris patients. Methods, This randomized, double-blind, placebo-controlled study compares nightly topical application of RA/,-CD complex hydrogel formulation (0.025%), RA/,-CD complex in moisturizing base (0.025%), hydrogel base, moisturizer base or a commercial RA gel (0.05%) in acne vulgaris patients. Improvement of acne was assessed using a 5-point improvement scale and by measuring sebum and moisture content of the skin using an SM 810 sebumeter/corneometer. Results, After 3 months of treatment, mean scores of acne improvement on the 5-point scale were 4 with the RA/,-CD complex hydrogel formulation, 4.1 with the RA/,-CD complex in moisturizing base, 1.2 with hydrogel placebo base, 1.1 with moisturizer placebo base and 3 with the commercial RA product. All patients treated with the commercial product experienced local side-effects. One patient discontinued due to severe irritation. None of the patients treated with the RA/,-CD complex in the moisturizing base and hydrogel formulation experienced significant local irritation, although the sebum content of the skin decreased after application of the RA/,-CD preparations. This change was not significant compared to controls. The moisture content of the skin was better preserved in the group treated with the RA/,-CD complex in the moisturizing base. Conclusion, The topical RA/,-CD complex, in hydrogel and moisturizing base, was more effective than the twice concentrated commercial RA product. There were few topical side-effects with this new formulation, which increases patient compliance. Topical RA/,-CD (0.025% RA) did not significantly reduce sebum secretion but may help to preserve optimum epidermal moisture content with the proper base formulation. This is the first study in the literature reporting efficacy and tolerability of the topical RA/,-CD complex in acne vulgaris. We conclude that the topical RA/,-CD complex displays an improved efficacy and tolerability profile and is an effective treatment alternative for acne vulgaris. [source] Synthesis and anthelmintic activity of thioamide analogues of cyclic octadepsipeptides such as PF1022APEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 11 2001Peter Jeschke Abstract The tetra - and mono -thionated cyclic octadepsipeptides represent novel cyclic octadepsipeptide derivatives with broad-spectrum activity against parasitic nematodes in mice and sheep. Some of these show better activity than the potent natural anthelmintic cyclic octadepsipeptide PF1022A against Hymenolepis nana, Heterakis spumosa and Trichinella spiralis larvae in mice. In particular, they show improved efficacy against Haemonchus contortus and Trichostrongylus colubriformis in sheep compared with PF1022A. Here we report on two different and simple synthetic pathways for this new class of thionated cyclic octadepsipeptides. © 2001 Society of Chemical Industry [source] Current drug treatments for female urinary incontinencePRESCRIBER, Issue 23 2006Tarang Majmudar MRCOG Several new drug treatments are now marketed for incontinence with improved efficacy and reduced side-effects. Our Drug review discusses the range of drugs currently available to treat this condition, followed by a review of prescription data, sources of further information and the Datafile. Copyright © 2006 Wiley Interface Ltd [source] ORIGINAL RESEARCH,ED PHARMACOTHERAPY: Sildenafil Citrate 100 mg Starting Dose in Men with Erectile Dysfunction in an International, Double-Blind, Placebo-Controlled Study: Effect on the Sexual Experience and Reducing Feelings of Anxiety About the Next Intercourse AttemptTHE JOURNAL OF SEXUAL MEDICINE, Issue 10 2009Oleg B. Loran MD ABSTRACT Introduction., Sildenafil citrate 50 mg is the recommended starting dose for men with erectile dysfunction (ED); however, most men are later titrated to sildenafil 100 mg for improved efficacy. Aim., Assess the tolerability and efficacy of sildenafil initiated at the 100-mg dose in men with ED. Methods., Men with ED (score ,25 on the Erectile Function domain of the International Index of Erectile Function) who had received ,6 total doses of a phosphodiesterase type 5 inhibitor and none within 4 weeks were randomized to 8 weeks of double-blind, placebo-controlled (DBPC), fixed-dose treatment (50 or 100 mg sildenafil or placebo) followed by 4 weeks of open-label flexible-dose sildenafil (50 or 100 mg). Main Outcome Measures., Efficacy, tolerability, treatment satisfaction, and other end points were measured at baseline and/or the end of the double-blind and open-label phases and compared between placebo and sildenafil initiated at doses of 50 and 100 mg. Results., Improvements in DBPC patient-reported outcomes from baseline were statistically significant for both sildenafil 50 and 100 mg compared with placebo. At the end of DBPC treatment, 56% of men on the 100-mg dose felt no anxiety about the next intercourse attempt compared with 39% in the 50-mg group (odds ratio 2.03; P = 0.0197). Changes in functional scores from baseline were not statistically significant with the 100-mg dose compared with the 50-mg dose in the DBPC. Measures of treatment satisfaction and sexual experience significantly favored the 100-mg dose compared with the 50-mg dose in the DBPC. There was no increase in adverse events with the higher dose. Conclusions., Sildenafil at 50 mg or 100 mg significantly improved erection quality, treatment satisfaction, anxiety levels, and the sexual experience compared with placebo during DBPC. Sildenafil 100 mg improved the sexual experience and treatment satisfaction, and reduced feelings of anxiety compared with the 50-mg dose. Loran OB, Ströberg P, Lee SW, Park NC, Kim SW, Tseng LJ, Collins S, and Stecher VJ. Sildenafil citrate 100 mg starting dose in men with erectile dysfunction in an international, double-blind, placebo-controlled study: Effect on the sexual experience and reducing feelings of anxiety about the next intercourse attempt. J Sex Med 2009;6:2826,2835. [source] Superior efficacy of a Cremophor-free albumin-bound paclitaxel compared with solvent-based paclitaxel in Chinese patients with metastatic breast cancerASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 3 2009Zhong-Zhen GUAN Abstract Aim: In a previous study, a 130-nm nanoparticle albumin-bound paclitaxel (nab -paclitaxel) demonstrated improved efficacy and safety profile compared with solvent-based paclitaxel (sb-paclitaxel) in Caucasian patients with metastatic breast cancer (MBC). The aim of the present randomized study was to compare the response rates and safety profile of nab -paclitaxel with sb-paclitaxel in Chinese patients with MBC. Methods: In the present open-label, multicenter study, 210 patients with MBC were randomly assigned to receive nab -paclitaxel 260 mg/m2 intravenously (i.v.) over 30 min every 3 weeks (q3w) with no premedication or sb-paclitaxel 175 mg/m2 i.v. over 3 h q3w with standard premedication. Results: The overall response rate was 54 and 29% in patients treated with nab -paclitaxel and sb-paclitaxel, respectively (P < 0.001). nab -paclitaxel induced a higher response rate in patients who were <65 years old, patients who were receiving first-line therapy, patients who had no prior anthracycline therapy, patients who had , or >3 metastatic lesions, and patients who had visceral disease. The progression-free survival (PFS) period was 7.6 months for nab -paclitaxel and 6.2 months for sb-paclitaxel (P = 0.118). Despite the 49% higher paclitaxel dose in patients receiving nab -paclitaxel compared with patients receiving sb-paclitaxel, the safety profile was similar in both treatment groups. The most common grades 3 and 4 adverse event (AE) in both arms was neutropenia. The most common grade 3 nonhematologic AE was peripheral neuropathy, and no grade 4 peripheral neuropathy was observed. Conclusion: Compared with sb-paclitaxel, nab -paclitaxel demonstrated superior efficacy, an acceptable safety profile, and a trend toward increased PFS in patients with MBC. [source] Recombinant, ETA,-based CD64 immunotoxins: improved efficacy by increased valency, both in vitro and in vivo in a chronic cutaneous inflammation model in human CD64 transgenic miceBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2010T. Ribbert Summary Background, Dysregulated, activated macrophages play a pivotal role in chronic inflammatory diseases such as arthritis and atopic dermatitis. These cells display increased expression of the high-affinity Fc, receptor (CD64), making them ideal targets for CD64-specific immunotoxins. We previously showed that a chemically linked immunotoxin, the monoclonal H22-RicinA, specifically eliminated infiltrating activated macrophages and resolved chronic cutaneous inflammation. However, several disadvantages are associated with classic immunotoxins, and we therefore followed a fusion protein strategy to express the antigen-binding site alone (scFv H22) fused to a derivative of Pseudomonas exotoxin A (ETA,). Objectives, To assess the potential effect of increased valency on efficacy, we produced monovalent [H22(scFv)-ETA,] and bivalent [H22(scFv)2 -ETA,] versions and evaluated their potential for eliminating activated macrophages both in vitro and in vivo. Methods, Both immunotoxins were produced by bacterial fermentation. Binding was assessed by flow cytometry on the monocytic CD64+ cell line U937. Toxicity was analysed by XTT and apoptosis induction by annexin V bioassay. The in vivo effect was tested in a human CD64 transgenic mouse model for cutaneous inflammation. Results, The cytotoxic effects of both immunotoxins were clearly due to apoptosis with an IC50 of 140 pmol L,1 for monovalent and only 14 pmol L,1 for the divalent version. In vivo treatment with H22(scFv)-ETA, reduced CD64+ activated macrophages to 21% of their initial numbers whereas H22(scFv)2 -ETA, treatment reduced these cells to 4·8% (P < 0·001). Conclusions, These data clearly show increased efficacy due to increased valency of the anti-CD64 immunotoxin. Both recombinant immunotoxins have a low IC50, making them suitable for the treatment of diseases involving dysregulated, activated macrophages. [source] Boron Neutron Capture Therapy for glioblastoma multiforme: advantage of prolonged infusion of BPA-fACTA NEUROLOGICA SCANDINAVICA, Issue 1 2010K. Sköld Sköld K, H-Stenstam B, Diaz AZ, Giusti V, Pellettieri L, Hopewell JW. Boron Neutron Capture Therapy for glioblastoma multiforme: advantage of prolonged infusion of BPA-f. Acta Neurol Scand: 2010: 122: 58,62. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives,,, To assess possible improved efficacy of Boron Neutron Capture Therapy (BNCT) for glioblastoma multiforme (GBM) using prolonged infusion and a correspondingly higher dose of l-boronophenylalanine, as the fructose complex (BPA-f). Materials and methods,,, The benefit of prolonged infusion was analyzed by comparing the results from a Phase II study using 6 h infusion of BPA-f with those obtained from a Phase I/II study using 2 h of infusion. Median survival time (MST) from diagnosis, patient baseline characteristics, salvage treatment and severe adverse events were considered in the comparison. Results,,, MST increased significantly, from 12.8 (95% confidence interval or CI: 10.3,14.0) months with 2 h infusion to 17.7 (95% CI: 13.6,19.9) months with 6 h of infusion. The fraction of patients with WHO grade 3,4 adverse events was similar in the two studies at 13% and 14%, respectively. Conclusion,,, Prolonged infusion was found to be beneficial for the efficacy of BNCT and it is suggested that 6 h infusion of BPA-f should be used in future trials of BNCT for GBM. BNCT, which is a single-day treatment with mild side effects, should be assessed in a controlled trial, as an alternative to 30 daily fractions of conventional fractionated photon therapy over a period of 6 weeks. [source] | |||||||||||||||||||||||||