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High Efficacy (high + efficacy)
Selected AbstractsHigh Efficacy of Ranitidine Bismuth Citrate, Amoxicillin, Clarithromycin and Metronidazole Twice Daily for Only Five Days in Helicobacter pylori EradicationHELICOBACTER, Issue 2 2001Javier P. Gisbert ABSTRACT Aim. The combination of a proton pump inhibitor (PPI) or ranitidine-bismuth-citrate (Rbc) and two antibiotics for 7,10 days are, at present, the preferred treatments in Helicobacter pylori eradication. However, therapies for fewer than 7 days have been scarcely evaluated and it is unknown whether the length of treatment can be shortened, without a lost of efficacy, if three instead of two antibiotics are used. The aim of our study was to evaluate the efficacy of Rbc plus three antibiotics for only 5 days in H. pylori eradication. Methods. We prospectively studied 80 patients (34% duodenal ulcer, 66% functional dyspepsia) infected by H. pylori. At endoscopy, biopsies were obtained for histological study and rapid urease test, and a 13C-urea breath test was carried out. Urea breath test was repeated 4 weeks after completing eradication treatment with Rbc [400 mg twice a day (bid)], amoxicillin (1 g bid), clarithromycin (500 mg bid) and metronidazole (500 mg bid). All drugs were administered together after breakfast and dinner for 5 days only, and no treatment was administered thereafter. Compliance with therapy was determined from the interrogatory and the recovery of empty envelopes of medications. Results. In 79 out of the 80 patients, H. pylori eradication success or failure was assessed after therapy (one patient was lost from follow-up). All but one of these 79 patients took all the medications (one patient stopped treatment on the day 3 due to nausea/vomiting). Per protocol eradication was achieved in 72/78 (92%; 95% CI, 84,96%) and in 72/80 (90%; 81,95%) by intention-to-treat. Therapy was more effective in patients with duodenal ulcer than in those with functional dyspepsia [100% (87,100%) vs. 85% (73,92%) by intention-to-treat; p < .05]. Adverse effects were described in ten patients (12%), and included the perception of a metallic taste (eight patients), nausea/vomiting (two patients, one of them abandoned the treatment due to this), and diarrhea (two patients). Conclusion. The combination of Rbc, amoxicillin, clarithromycin and metronidazole for only 5 days represents a promising therapy for H. pylori infection, due to its high efficacy, simple posology, low cost and excellent tolerance. [source] Photodynamic Therapy for the Treatment of Cutaneous Neoplasia, Inflammatory Disorders, and PhotoagingDERMATOLOGIC SURGERY, Issue 5 2009EMILY TIERNEY MD BACKGROUND Photodynamic therapy (PDT) has demonstrated high efficacy, minimal side effects, and improved cosmetic outcome when used for the treatment of actinic keratoses (AK), basal cell carcinoma (BCC), squamous cell carcinoma, and photoaging. METHODS To review the literature on the use of PDT in dermatologic surgery using MEDLINE. RESULTS Published clinical studies using PDT in the treatment of AKs yield overall efficacy rates ranging from 50% to 71% with one treatment to as high as 88% to 90% with two or more treatments. For superficial BCC, initial clearance rates were 76% to 97%, and for Bowen's disease, initial clearance rates ranged from 72% to 94% overall. The use of PDT for photorejuvenation is a relatively new application of this technology, which has shown promise in improving the appearance of fine lines, pigmentary variation, and telangiectasias. CONCLUSIONS The advantages of photodynamic therapy include the capacity for noninvasive targeted therapy through topical application of aminolevulinic acid and methyl aminolevulinic acid, with outstanding cosmetic results. Although the theory behind the use of chemical photosensitizers and ultraviolet light to treat a wide variety of skin disorders is straightforward, the practical application of this technology is evolving. Additional research into the precise mechanisms of action for specific photosensitizers and optimal light sources will be highly beneficial to the advancement of this technology. [source] Efficacy of fine-needle aspiration biopsy in diagnosis of breast cancer: A retrospective study of 303 cases in BahrainDIAGNOSTIC CYTOPATHOLOGY, Issue 9 2009F.R.C.Path, Khalid Al-Sindi M.D. Abstract Breast cancer is a leading cause of death in many countries worldwide and breast lesions remain a common diagnostic dilemma. Fine-needle aspiration biopsy (FNAB) has been suggested as the most important, first line, minimally invasive measure in the management of patients with breast lesions. The aim of this study is to evaluate the efficacy of FNAB in patients with breast lesions by comparing the diagnostic accuracy of cytology results with that of the definitive histological examination outcome and also to investigate the added value of a single aspirator experience to the overall diagnostic precision and compared with the internationally published results. A retrospective study of 303 breast FNAB samples were carried out by a single experienced cytopathologist with complete comparison records. The prevalence of positive cytologic diagnosis for the breast cancer was determined to be 20.4%. The overall diagnostic accuracy of FNAB was 97.9%, with a specificity and sensitivity of 98.3 and 96.5%, respectively. The overall positive and negative predictive values were determined to be 93.2 and 99.2%, respectively. In addition, the sensitivity was comparable in cases that have been attempted by palpation-guided sampling compared with those aspirations that were carried out under US guidance. Results from this study confirm that FNAB biopsies performed and reported by a dedicated, single, skilled cytopathologist are highly effective in diagnosis of breast lesions and reliable in differentiating benign and malignant breast lesions with an overall high efficacy in a specialized laboratory-based FNAB clinic. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] Early behavioral screening for antidepressants and anxiolyticsDRUG DEVELOPMENT RESEARCH, Issue 9 2006Vincent Castagné Abstract Early preclinical behavioral testing is an essential stage during the development of substances with potential antidepressant and/or anxiolytic activity. With the growing cost of drug development, optimal research strategies are needed to detect potential new treatments with high efficacy and minimal side effects and to confirm in vitro pharmacological studies. In the following article, we present simple rodent tests used for early behavioral testing for antidepressant-like and anxiolytic-like activity. Unpublished results from our laboratory are discussed with reference to published data to illustrate the predictive validity of several behavioral screening tests. Drug Dev. Res. 67:729,742, 2006. © 2006 Wiley-Liss, Inc. [source] Evaluation of an action threshold-based IPM wheat model in Rheinland (Germany) in 1999/2001,EPPO BULLETIN, Issue 3 2003M. Heger Under the specific agricultural and climatic conditions of Rheinland (DE), 48 field trials in three years demonstrated the practicability of the action threshold-based fungicide strategy of the IPM wheat model. The underlying data for action thresholds and dosage of fungicides applied are outlined. The cereal pathogens concerned, predominantly Mycosphaerella graminicola and Puccinia recondita, were controlled in the early stages of epidemic development using reduced rates of fungicides. The IPM wheat model gave a high efficacy of control, in terms of disease incidence and disease severity, under both low and high disease pressure conditions. The yield levels resulting from this effective reduction in diseases were nearly the same as those of the disease-free variant. Total yield increase varied between 15% and 30% with an overall average of around 20%, and resulted in monetary benefits of 50,100 EUR ha,1 in the years considered. [source] Autologous transplantation in relapsed and refractory Hodgkin's diseaseEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2005Andreas Josting Abstract:, The current data support the use of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) as standard procedure for the majority of patients with Hodgkin's disease (HD) relapsing or progressing after combination chemotherapy. Prognostic factors reflecting unfavourable prognostic features of the disease as well as resistance to conventional salvage therapy have been identified. Preliminary data suggests a high efficacy of high-dose sequential chemotherapies in these patients. An ongoing randomized trial is comparing standard HDCT versus sequential HDCT in patients with relapsed HD. [source] Inhibition of urokinase receptor gene expression and cell invasion by anti-uPAR DNAzymes in osteosarcoma cellsFEBS JOURNAL, Issue 14 2005Charles E. De Bock The urokinase-type plasminogen activator (uPA) receptor (uPAR) has been implicated in signal transduction and biological processes including cancer metastasis, angiogenesis, cell migration, and wound healing. It is a specific cell surface receptor for its ligand uPA, which catalyzes the formation of plasmin from plasminogen, thereby activating the proteolytic cascade that contributes to the breakdown of extracellular matrix, a key step in cancer metastasis. We have synthesized three different DNA enzymes (Dz372, Dz483 and Dz720) targeting uPAR mRNA at three separate purine (A or G),pyrimidine (U or C) junctions. Two of these DNAzymes, Dz483 and Dz720, cleaved uPAR transcript in vitro with high efficacy and specificity at a molar ratio (uPAR to Dz) as low as 1 : 0.2. When analyzed over 2 h with a 200-fold molar excess of DNAzymes to uPAR transcript, Dz720 and Dz483 were able to decrease uPAR transcript in vitro by ,,93% and ,,84%, respectively. They also showed an ability to cleave uPAR mRNA in the human osteosarcoma cell line Saos-2 after transfection. The DNAzyme Dz720 decreased uPAR mRNA within 4 h of transfection, and inhibited uPAR protein concentrations by 55% in Saos-2 cells. The decrease in uPAR mRNA and protein concentrations caused by Dz720 significantly suppressed Saos-2 cell invasion as assessed by an in vitro Matrigel assay. The use of DNAzyme methodology adds a new potential clinical agent for decreasing uPAR mRNA expression and inhibiting cancer invasion and metastasis. [source] High Efficacy of Ranitidine Bismuth Citrate, Amoxicillin, Clarithromycin and Metronidazole Twice Daily for Only Five Days in Helicobacter pylori EradicationHELICOBACTER, Issue 2 2001Javier P. Gisbert ABSTRACT Aim. The combination of a proton pump inhibitor (PPI) or ranitidine-bismuth-citrate (Rbc) and two antibiotics for 7,10 days are, at present, the preferred treatments in Helicobacter pylori eradication. However, therapies for fewer than 7 days have been scarcely evaluated and it is unknown whether the length of treatment can be shortened, without a lost of efficacy, if three instead of two antibiotics are used. The aim of our study was to evaluate the efficacy of Rbc plus three antibiotics for only 5 days in H. pylori eradication. Methods. We prospectively studied 80 patients (34% duodenal ulcer, 66% functional dyspepsia) infected by H. pylori. At endoscopy, biopsies were obtained for histological study and rapid urease test, and a 13C-urea breath test was carried out. Urea breath test was repeated 4 weeks after completing eradication treatment with Rbc [400 mg twice a day (bid)], amoxicillin (1 g bid), clarithromycin (500 mg bid) and metronidazole (500 mg bid). All drugs were administered together after breakfast and dinner for 5 days only, and no treatment was administered thereafter. Compliance with therapy was determined from the interrogatory and the recovery of empty envelopes of medications. Results. In 79 out of the 80 patients, H. pylori eradication success or failure was assessed after therapy (one patient was lost from follow-up). All but one of these 79 patients took all the medications (one patient stopped treatment on the day 3 due to nausea/vomiting). Per protocol eradication was achieved in 72/78 (92%; 95% CI, 84,96%) and in 72/80 (90%; 81,95%) by intention-to-treat. Therapy was more effective in patients with duodenal ulcer than in those with functional dyspepsia [100% (87,100%) vs. 85% (73,92%) by intention-to-treat; p < .05]. Adverse effects were described in ten patients (12%), and included the perception of a metallic taste (eight patients), nausea/vomiting (two patients, one of them abandoned the treatment due to this), and diarrhea (two patients). Conclusion. The combination of Rbc, amoxicillin, clarithromycin and metronidazole for only 5 days represents a promising therapy for H. pylori infection, due to its high efficacy, simple posology, low cost and excellent tolerance. [source] The Role of Anxiety in Seeking and Retaining Risk Information: Testing the Risk Perception Attitude Framework in Two StudiesHUMAN COMMUNICATION RESEARCH, Issue 2 2006Monique Mitchell Turner Despite the importance of health information seeking, not all people engage in such behaviors, especially when thinking about the disease is distressing. The focus of this paper is to examine the antecedents of information seeking and retention. Based on individuals' risk perception and efficacy beliefs, the risk perception attitude framework is used to formulate four groups: responsive (high risk, high efficacy), avoidance (high risk, low efficacy), proactive (low risk, high efficacy), and indifference (low risk, low efficacy). In Study 1, a 2 (risk) × 2 (efficacy) between-subjects experiment, participants' perceived risk to skin cancer and skin cancer,related efficacy beliefs were induced to determine their information seeking, retention, and intentions to engage in future seeking. The responsive group, as predicted, was associated with the most information-seeking behaviors and information-seeking intentions. The avoidance group, however, sought information but exhibited the lowest retention scores. These results were used to derive two predictions,the incredulity hypothesis and the anxiety-reduction hypothesis,that were then tested in Study 2. Study 2, also a 2 (risk) × 2 (efficacy) between-subjects experiment dealing with diabetes, found support for the anxiety-reduction hypothesis, which argues that the high-risk, low-efficacy group experiences more anxiety, which leads to high motivations to seek, but lower ability to retain information. [source] Perceived Risk and Efficacy Beliefs as Motivators of ChangeHUMAN COMMUNICATION RESEARCH, Issue 3 2003Use of the Risk Perception Attitude (RPA) Framework to Understand Health Behaviors Evidence of a direct correlation between risk perception and self-protective behavior is ambiguous at best. Witte's (1992, 1994) extended parallel process model (EPPM) explains many contradictory findings by pointing out the moderating role played by efficacy beliefs. Working from the EPPM, this article introduces the risk perception attitude (RPA) framework that categorizes individuals into one of four attitudinal groups: responsive (high risk, high efficacy), avoidance (high risk, low efficacy), proactive (low risk, high efficacy), and indifference (low risk, low efficacy). We conducted two studies to test our hypotheses that these groups differ in their self-protective motivation, intention to seek information, behavioral intention, knowledge acquisition, and time spent seeking information. Results, though not entirely consistent, suggest that, when risk and efficacy are made salient (Study 1), people's risk perception guides most of their subsequent actions, but in a natural context (Study 2), risk and efficacy jointly affect subsequent action. [source] Clinical correlates of clozapine prescription for schizophrenia in ChinaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 1 2007Yu-tao Xiang Abstract Aims Few studies have investigated the prescription patterns of clozapine in outpatients with schizophrenia in China. It is an important issue due to clozapine's high efficacy and potentially fatal side effect profile. This study examined the use of clozapine and its correlates in China. Methods Three hundred ninety-eight clinically stable outpatients with schizophrenia were randomly selected and interviewed in Hong Kong (HK) and Beijing (BJ). Assessment instruments included the Structured Clinical Interview for DSM-IV, Brief Psychiatric Rating Scale, Simpson and Angus Scale of Extrapyramidal Symptoms, Barnes Akathisia Rating Scale and the Hong Kong and Mainland China World Health Organization Quality of Life Schedule-Brief version. Assessments were performed by the same investigator in both sites. Results Clozapine was prescribed to 15.6% of (n,=,62) patients. There was a wide inter-site variation between HK and BJ. Use of clozapine was associated with age, age at onset, extrapyramidal side effects (EPS), having health insurance, use of depot and typical antipsychotic and anticholinergic drugs and benzodiazepines as well as history of suicidal attempts. On multiple logistic regression analysis, the number of hospitalizations, site (HK vs. BJ), use of typical antipsychotics, polypharmacy and co-prescription with anticholinergics were significantly associated with the prescription of clozapine. No significant differences were found between the clozapine and non-clozapine groups with regard to any of the quality of life domains. Conclusion A combination of economical and clinical factors, health policies and the characteristics of the treatment settings plays important roles in determining clozapine use. Clozapine appears to have little significant influence on quality of life in clinical stable Chinese patients with schizophrenia. Copyright © 2007 John Wiley & Sons, Ltd. [source] The therapeutic profile of zolmitriptan in clinical practiceINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 8 2004H.C. Diener Summary The efficacy and tolerability of the 5-HT1B/1D -receptor agonist zolmitriptan was evaluated in an open post-marketing surveillance study in 12,919 patients, treating 36,510 migraine attacks. Mean visual analogue scale scores for pain decreased (6.9,2.2; 68% improvement) and scores for impairment of normal activities decreased (6.6,2.2; 67% improvement) at 2 h after dose. Non-headache symptoms of migraine resolved in 73,86% of attacks. Improvement was achieved within 2 h in >80% of attacks and within 1 h in 37% of attacks. This high level of efficacy was achieved with a single 2.5 mg dose in 95% of attacks. Compared with previous migraine treatments, 85% of patients preferred zolmitriptan for efficacy and 56% for better tolerability. Corresponding preference rates were 87 and 63% when compared with ergot alkaloids. Adverse events occurred in 2% of patients and were either typical class effects or known symptoms and complications of migraine. These results provide evidence for the high efficacy and good tolerability of the 2.5 mg dose of zolmitriptan in clinical practice in migraine. Zolmitriptan was very well tolerated, with patients expressing a distinct preference for zolmitriptan over previous treatments. [source] Processed kaolin as an alternative insecticide against the European pear sucker, Cacopsylla pyri (L.)JOURNAL OF APPLIED ENTOMOLOGY, Issue 7 2005C. Daniel Abstract:, Application of processed kaolin particle film (Surround® WP; Engelhard Corporation, Iselin, NJ, USA) repels insects without lethal effects; hence side effects on beneficial arthropods are low. Processed kaolin may be an alternative to broad-spectrum insecticides used against European pear sucker, Cacopsylla pyri (L.), in organic and conventional pear production. A small-plot field trial was conducted in spring 2003 to assess this hypothesis. Multiple applications of processed kaolin during the first flying period of C. pyri significantly reduced the number of nymphs compared to the untreated control. Processed kaolin protected pear trees at least as good as the standard organic insecticide rotenone. Since the effects on the summer population could not be assessed in this small-plot trial due to the high mobility of the adult C. pyri, a large-plot trial was conducted in 2004. Thereby, the processed kaolin showed a very high efficacy and the population of C. pyri was kept under a damaging level over the whole season. At the end of June the population density of C. pyri in the processed kaolin treated area was lower than in the IPM treated plot. In conclusion, kaolin shows promise as an alternative control for C. pyri in organic and IPM orchards. [source] Comparative effects of some botanicals for the control of the seed weevil Caryedon serratus Olivier (Col., Bruchidae)JOURNAL OF APPLIED ENTOMOLOGY, Issue 10 2002H. A. El Atta Leaf powder, seed kernel powder and oil extracted from the seeds of A. indica and leaf powder and oil extracted from the leaves of E. camaldulensis and benzene hexachloride (BHC) were tested at 1, 3 and 5% (w/w or v/w) against C. serratus. Eucalyptus leaf oil (ELO) and neem oil (NO) at 3 and 5% were as efficient as BHC and significantly (P=0.0001) reduced egg laying by C. serratus, whereas Eucalyptus leaf powder (ELP) had no significant effect. Neem seed kernel powder (NSKP) at 5%, ELO (3 and 5%) and NO (3 and 5%) significantly (P=0.0001) reduced egg hatching more than BHC at all doses. NO (3 and 5%) and ELO (3 and 5%) significantly (P=0.0001) reduced larval development more than BHC, whereas ELP and Neam Leaf Powder had no significant effect. Adult emergence and mortality were also significantly (P=0.0001) affected by some botanicals tested, especially oils. Oils were more effective as compared with powder. The study indicated that the botanicals tested have a good potential in replacing conventional pesticides because of their high efficacy and environmental safety. [source] Antimicrobial activity of essential oils and structurally related synthetic food additives towards selected pathogenic and beneficial gut bacteriaJOURNAL OF APPLIED MICROBIOLOGY, Issue 2 2006W. Si Abstract Aims:, To assess the potential of essential oils and structurally related synthetic food additives in reducing bacterial pathogens in swine intestinal tract. Methods and Results:, The antimicrobial activity of essential oils/compounds was measured by determining the inhibition of bacterial growth. Among 66 essential oils/compounds that exhibited ,80% inhibition towards Salmonellatyphimurium DT104 and Escherichia coli O157:H7, nine were further studied. Most of the oils/compounds demonstrated high efficacy against S. typhimurium DT104, E. coli O157:H7, and E. coli with K88 pili with little inhibition towards lactobacilli and bifidobacteria. They were also tolerant to the low pH. When mixed with pig cecal digesta, these oils/compounds retained their efficacy against E. coli O157:H7. In addition, they significantly inhibited E. coli and coliform bacteria in the digesta, but had little effect on the total number of lactobacilli and anaerobic bacteria. Conclusions:, Some essential oils/compounds demonstrated good potential, including efficacy, tolerance to low pH, and selectivity towards bacterial pathogens, in reducing human and animal bacterial pathogens in swine intestinal tract. Significance and Impact of the Study:, This study has identified candidates of essential oils/compounds for in vivo studies to develop antibiotic substitutes for the reduction of human and animal bacterial pathogens in swine intestinal tract. [source] Cloning and molecular dissection of the 8.8 kb pig uroplakin II promoter using transgenic mice and RT4 cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2006Deug-Nam Kwon Abstract Uroplakin II (UPII) gene expression is highly tissue and cell specific, with mRNA present in the suprabasal cell layers of the bladder and urethra. Previous reports described the mouse UPII (mUPII) promoter as primarily urothelium selective. However, ectopic expression of a transgene under the 3.6 kb mUPII promoter was also detected in brain, kidney, and testis in some transgenic mouse lines. Here, we have cloned an 8.8 kb pig UPII (pUPII) promoter region and investigated which cells within the bladder and urethra express a transgene consisting of the pUPII promoter fused to human erythropoietin (hEPO) or a luciferase gene. pUPII-luciferase expression vectors with various deletions of the promoter region were introduced into mouse fibroblast (NIH3T3), Chinese hamster ovary (CHO), and human bladder transitional carcinoma (RT4). A 2.1 kb pUPII promoter fragment displayed high levels of luciferase activity in transiently transfected RT4 cells, whereas the 8.8 kb pUPII promoter region displayed only low levels of activity. The pUPII-hEPO expression vector was injected into the pronucleus of zygotes to make transgenic mice. To elucidate the in vivo molecular mechanisms controlling the tissue- and cell-specific expression of the pUPII promoter gene, transgenic mice containing 2.1 and 8.8 kb pUPII promoter fragments linked to the genomic hEPO gene were generated. An erythropoietin (EPO) assay showed that all nine transgenic lines carrying the 8.8 kb construct expressed recombinant human erythropoietin (rhEPO) only in their urethra and bladder, whereas two transgenic lines carrying the 2.1 kb pUPII promoter displayed hEPO expression in several organs including bladder, kidney, spleen, heart, and brain. These studies demonstrate that the 2.1 kb promoter contains the DNA elements necessary for high levels of expression, but lacks critical sequences necessary for tissue-specific expression. We compared binding sites in the 2.1 and 8.8 kb promoter sequences and found five peroxisome proliferator responsive elements (PPREs) in the 8.8 kb promoter. Our data demonstrated that proliferator-activated receptor (PPAR)-, activator treatment in RT4 cells induced the elevated expression of hEPO mRNA under the control of the 8.8 kb pUPII promoter, but not the 2.1 kb promoter. Collectively, our data suggested that all the major trans-regulatory elements required for bladder- and urethra-specific transcription are located in the 8.8 kb upstream region and that it may enhance tissue-specific protein production and be of interest to clinicians who are searching for therapeutic modalities with high efficacy and low toxicity. J. Cell. Biochem. 99: 462,477, 2006. © 2006 Wiley-Liss, Inc. [source] An alternate-day corticosteroid regimen for pemphigus vulgaris.JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2007A 13-year prospective study Abstract Background, Pemphigus vulgaris (PV) at the early, usually oral and relatively stable stage, represents the majority of PV patients. Treatment modalities usually do not differ compared to those for the fully established disease. Objectives, To prospectively assess a standardized and effective therapeutic approach that aims at less morbidity due to adverse reactions. Methods, The following regimen, also known as Lever's mini treatment (LMT), was used. Forty mg of oral prednisone on alternate days plus 100 mg azathioprine every day were administered until the complete healing of all lesions. A gradual monthly and later bimonthly decrease of prednisone was followed by the tapering of a second immunosuppressive agent, in a one-year period. Results, Seventy-four patients suffering from early-stage-PV, and representing 70% of all PV patients seen through the years 1991,2003, were eligible in the study. Total follow-up period was 76 ± 37 (26,180) months. During the 53 ± 26 months of LMT, 6 (8%) patients dropped out of therapy, 9 (12%) required a change to another treatment, two (3%) died and 57 (77%) achieved a lesion-free condition. Forty-five (61%) patients were in complete remission for 27 ± 29 months. Significant morbidity was estimated 4/74 (5.2%). Disease ,breakthroughs' necessitating treatment adjustments occurred in 30 patients, usually throughout the last phase of therapy and post-treatment follow-up. Conclusion, LMT may be a standardized therapeutic approach for the early and relatively stable stage of PV, resulting in high efficacy, safety and quality of life profile. [source] Review article: new receptor targets for medical therapy in irritable bowel syndromeALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010M. CAMILLERI Summary Background, Despite setbacks to the approval of new medications for the treatment of irritable bowel syndrome, interim guidelines on endpoints for irritable bowel syndrome (IBS) trials have enhanced interest as new targets for medical therapy are proposed based on novel mechanisms or chemical entities. Aims, To review the approved lubiprostone, two targets that are not meeting expectations (tachykinins and corticotrophin-releasing hormone), the efficacy and safety of new 5-HT4 agonists, intestinal secretagogues (chloride channel activators, and guanylate cyclase-C agonists), bile acid modulation, anti-inflammatory agents and visceral analgesics. Methods, Review of selected articles based on PubMed search and clinically relevant information on mechanism of action, safety, pharmacodynamics and efficacy. Results, The spectrum of peripheral targets of medical therapy addresses chiefly the bowel dysfunction of IBS and these effects are associated with pain relief. The pivotal mechanisms responsible for the abdominal pain or visceral sensation in IBS are unknown. The new 5-HT4 agonists are more specific than older agents and show cardiovascular safety to date. Secretory agents have high specificity, low bioavailability and high efficacy. The potential risks of agents ,borrowed' from other indications (such as hyperlipidaemia, inflammatory bowel disease or somatic pain) deserve further study. Conclusions, There is reason for optimism in medical treatment of IBS with a spectrum of agents to treat bowel dysfunction. However, visceral analgesic treatments are still suboptimal. [source] Abundance of stable flies on heifers treated for control of horn flies with organophosphate impregnated ear tagsMEDICAL AND VETERINARY ENTOMOLOGY, Issue 1 2004A. A. Guglielmone Abstract., Ear tags containing 40% organophosphate insecticides (diazinon or diazinon plus chlorpyrifos-ethyl) were applied to control Haematobia irritans (L.) (Diptera: Muscidae) in treated (TG01 and TG02) and untreated (UG01 and UG02) groups of Holstein heifers born in 2001 and 2002, respectively. Control and treated groups were assessed for the abundance of Stomoxys calcitrans (L.) (Diptera: Muscidae) from August 2001 to April 2002 and again from August 2002 to April 2003. The treatment had a high efficacy for control of horn flies (maximum median number per heifer of TG01 and TG02 = 5) but a low effect on the abundance of stable flies. The total numbers of S. calcitrans were 1251 (42.9% of the total) and 1668 (57.1%) for TG01 and UG01, and 1423 (48.8%) and 1494 (51.2%) in TG02 and UG02, respectively. No significant difference in stable fly burden was found in 55 of the 76 weeks evaluated. A unimodal peak of abundance in the spring was found during the first fly season, and a bimodal abundance, with peaks in the spring and autumn, during the second season. No strong associations between horn fly and stable fly burdens was found in individuals of the CG01 (correlation coefficient = 0.13, P > 0.05) or CG02 (correlation coefficient = 0.538, P < 0.05, determination coefficient = 0.289). [source] Efficacy of topical griseofulvin in treatment of tinea corporisMYCOSES, Issue 3 2006Mohamed A. A. Kassem Summary Tinea infections are among the most common dermatological conditions throughout the world. Griseofulvin is a classical oral fungistatic antibiotic, active against Epidermophyton floccosum, Trichophyton and Microsporum species, the causative fungi of tinea corporis. To evaluate the efficacy of topical griseofulvin in the treatment of tinea circinata using three different vehicles for drug delivery. Sixteen patients with tinea circinata were instructed to apply either griseofulvin gel form in group A or a similar placebo gel for control group; a niosomal gel formulation of griseofulvin for group B or; a liposomal gel formulation of griseofulvin for group C. Patients were evaluated both clinically and mycologically after 3 weeks. Marked improvement was seen for groups A, B and C both clinically and mycologically while no improvement was observed in the placebo group. Mild and transient irritation was reported in four patients. Our results show that topical griseofulvin preparations may be effective and safe in treating tinea circinata and that further large-scale studies may establish the high efficacy of the niosomal gel formulation. [source] Resistance to cassava mosaic disease in transgenic cassava expressing antisense RNAs targeting virus replication genesPLANT BIOTECHNOLOGY JOURNAL, Issue 4 2005Peng Zhang Summary African cassava mosaic virus (ACMV) is a major contributor to cassava mosaic disease (CMD), the economically most important and devastating disease of cassava in Africa. We have developed transgenic cassava plants with increased ACMV resistance using improved antisense RNA technology by targeting the viral mRNAs of Rep (AC1), TrAP (AC2) and REn (AC3). Viral DNA replication assays in detached leaves demonstrated that replication of two ACMV isolates was strongly reduced or inhibited in most transgenic lines. After ACMV infection of plants using biolistic inoculation, several lines remained symptomless at lower infection pressure (100 ng viral DNA/plant). Symptom development was reduced and attenuated even at higher DNA doses. Transgenic ACMV-resistant plants had significantly reduced viral DNA accumulation in their infected leaves. Short sense and antisense RNAs specific to AC1 were identified in transgenic lines expressing AC1 antisense RNA, suggesting that the short RNAs mediate interference by post-transcriptional gene silencing. Our results demonstrate that resistance to ACMV infection of cassava can be achieved with high efficacy by expressing antisense RNAs against viral mRNAs encoding essential non-structural proteins, providing a new tool to combat CMD in Africa. [source] Extraction and Refinement Strategy for detection of autism in 18-month-olds: a guarantee of higher sensitivity and specificity in the process of mass screeningTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 8 2009Hideo Honda Background:, For early detection of autism, it is difficult to maintain an efficient level of sensitivity and specificity based on observational data from a single screening. The Extraction and Refinement (E&R) Strategy utilizes a public children's health surveillance program to produce maximum efficacy in early detection of autism. In the extraction stage, all cases at risk of childhood problems, including developmental abnormality, are identified; in the refinement stage, cases without problems are excluded, leaving only cases with conclusive diagnoses. Methods:, The city of Yokohama, Japan, conducts a routine child health surveillance program for children at 18 months in which specialized public health nurses administer YACHT-18 (Young Autism and other developmental disorders CHeckup Tool), a screening instrument to identify children at risk for developmental disorders. Children who screen positive undergo further observation, and those without disorders are subsequently excluded. To study the efficacy of early detection procedures for developmental disorders, including autism, 2,814 children born in 1988, examined at 18 months of age, and not already receiving treatment for diseases or disorders were selected. Results:, In the extraction stage, 402 (14.3%) children were identified for follow-up. In the refinement stage, 19 (.7%) of these were referred to the Yokohama Rehabilitation Center and diagnosed with developmental disorders. The extraction stage produced four false negatives, bringing total diagnoses of developmental disorders to 23 (.8%) , including 5 with autistic disorder and 9 with pervasive developmental disorder , not otherwise specified (PDDNOS). Sensitivity was 60% for autistic disorder and 82.6% for developmental disorders. Specificity for developmental disorders rose to 100% with the E&R Strategy. Picture cards used in YACHT-18 provided a finer screen that excluded some false positive cases. Conclusions:, An extraction and refinement methodology utilizing child health surveillance programs achieve high efficacy for early detection of autism. [source] Evaluation of Omeprazole in the Treatment of Reflux Laryngitis: A Prospective, Placebo-Controlled, Randomized, Double-Blind Study,THE LARYNGOSCOPE, Issue 12 2001J. Pieter Noordzij MD Abstract Objectives Proton-pump inhibitors are often recommended in the treatment of laryngitis secondary to gastric reflux. Despite prospective treatment studies reporting high efficacy, only one previous report has been placebo-controlled and blinded. The objective of this study was to determine the efficacy of omeprazole in treating proven reflux laryngitis. Study Design Prospective, placebo-controlled, randomized, double-blind clinical trial. Methods Fifty-three patients with one or more reflux laryngitis symptoms were recruited to undergo 24-hour dual-channel pH probe testing. Thirty patients with more than four episodes of laryngopharyngeal reflux were enrolled. By random assignment, 15 patients received 40 mg omeprazole twice a day and the other 15 received placebo for a period of 2 months. Symptoms (hoarseness, throat pain, lump in throat sensation, throat clearing, cough, excessive phlegm, dysphagia, odynophagia, and heartburn) and endoscopic laryngeal signs (erythema, edema, and mucus accumulation) were recorded initially, at 1 month, and 2 months. Results In general, most symptom scores improved over time for both the omeprazole and placebo groups. Hoarseness, when patients begin with low hoarseness symptom scores, and throat clearing improved significantly more in patients on omeprazole than in those on placebo during the 2-month study. Throat pain, lump in throat sensation, excessive phlegm, difficulty swallowing, pain with swallowing, and heartburn showed improvement in both treatment arms, signifying the possibility of a placebo effect. Endoscopic laryngeal signs did not change significantly over the course of the study for either treatment group. Conclusions A placebo effect appears to exist in the treatment of reflux laryngitis. However, hoarseness, when initially scored low, and throat clearing resulting from reflux laryngitis are effectively treated by omeprazole. [source] Efficacy of selection in sexually breeding Artemia (Artemia franciscana, Kellogg, 1906)AQUACULTURE RESEARCH, Issue 13 2006Mangesh M Shirdhankar Abstract Bi-directional selection for smaller naupliar size (SNS) and bigger naupliar size (BNS) was practiced to develop two divergent lines. The efficacy of bi-directional mass selection in Artemia franciscana was evaluated by comparing the predicted genetic gains with the realized genetic gains. Two sets of predictions were made using two heritability estimates, e.g., the heritability estimate from full-sib analysis (h2) and the estimate from regression of offspring on mid parent (bop). Predictions with the full-sib heritabilities were of very high magnitude as compared with predictions with bop heritabilities. The predictions based on bop were more or less in agreement with realized genetic gain, while the predictions with heritability estimates based on full-sib analysis were much higher than the realized gains. Ratios of realized gain to predicted gain based on full-sib heritabilities were 0.2302 and 0.2152, respectively, for males and females of the SNS line, and 0.0471 and 0.2248, respectively, for males and females of the BNS line. Ratios of realized gain to predicted gain based on bop were 1.5348 and 0.6069 for males and females of the SNS line and 0.1028 and 0.9503 for males and females of the BNS line. Ratios of realized gain to predicted gain based on full-sib heritability were of low magnitude in all the cases as the heritability estimates based on full-sib analysis were inflated by non-additive genetic variance. The ratios of realized gain to predicted gain based on bop were high in both sexes of SNS and females of BNS, indicating high efficacy of selection as bop includes only additive genetic variance. However, it was of low magnitude in BNS males. Thus, the heritability estimates based on regression of offspring on mid parent (bop) are more reliable than that of heritability estimates based on full-sib analysis (h2) for predicting the selection response in Artemia. [source] Antidepressants in the Treatment of Neuropathic PainBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2005Søren H. Sindrup Tricyclic antidepressants and anticonvulsants have long been the mainstay of treatment of this type of pain. Tricyclic antidepressants may relieve neuropathic pain by their unique ability to inhibit presynaptic reuptake of the biogenic amines serotonin and noradrenaline, but other mechanisms such as N-methyl-D-aspartate receptor and ion channel blockade probably also play a role in their pain-relieving effect. The effect of tricyclic antidepressants in neuropathic pain in man has been demonstrated in numerous randomised, controlled trials, and a few trials have shown that serotonin noradrenaline and selective serotonin reuptake inhibitor antidepressants also relieve neuropathic pain although with lower efficacy. Tricyclic antidepressants will relieve one in every 2,3 patients with peripheral neuropathic pain, serotonin noradrenaline reuptake inhibitors one in every 4,5 and selective serotonin reuptake inhibitors one in every 7 patients. Thus, based on efficacy measures such as numbers needed to treat, tricyclic antidepressants tend to work better than the anticonvulsant gabapentin and treatment options such as tramadol and oxycodone, whereas the serotonin noradrenaline reuptake inhibitor venlafaxine appears to be equally effective with these drugs and selective serotonin reuptake inhibitors apparently have lower efficacy. Head-to-head comparisons between antidepressants and the other analgesics are lacking. Contraindications towards the use of tricyclic antidepressants and low tolerability in general of this drug class , may among the antidepressants , favour the use of the serotonin noradrenaline reuptake inhibitors. A recent study on bupropion, which is a noradrenaline and dopamine uptake inhibitor, indicated a surprisingly high efficacy of this drug in peripheral neuropathic pain. In conclusion, antidepressants represent useful tools in neuropathic pain treatment and must still be considered as first line treatments of neuropathic pain. However, without head-to-head comparisons between antidepressants and other analgesics, it is not possible to provide real evidence-based treatment algorithms for neuropathic pain. [source] Photodynamic therapy of multiple actinic keratoses: reduced pain through use of visible light plus water-filtered infrared A compared with light from light-emitting diodesBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2010V. Von Felbert Summary Background, Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is an effective treatment for multiple actinic keratoses (AKs). Pain, however, is a major side-effect. Objectives, To compare pain intensity, efficacy, safety and cosmetic outcome of MAL PDT with two different light sources in an investigator-initiated, randomized, double-blind study. Methods, Eighty patients with multiple AKs grade I,II were assigned to two groups: group 1, MAL PDT with visible light and water-filtered infrared A (VIS + wIRA); group 2, MAL PDT with light from light-emitting diodes (LEDs), with a further division into two subgroups: A, no spray cooling; B, spray cooling on demand. MAL was applied 3 h before light treatment. Pain was assessed before, during and after PDT. Efficacy, side-effects, cosmetic outcome and patient satisfaction were documented after 2 weeks and 3, 6 and 12 months. Where necessary, treatment was repeated after 3 months. Results, Seventy-six of the 80 patients receiving MAL PDT completed the study. Patient assessment showed high efficacy, very good cosmetic outcome and high patient satisfaction. The efficacy of treatment was better in the group of patients without spray cooling (P = 0·00022 at 3 months, P = 0·0068 at 6 months) and showed no significant differences between VIS + wIRA and LED. VIS + wIRA was significantly less painful than LED: the median of maximum pain was lower in the VIS + wIRA group than in the LED group for PDT without spray cooling. Pain duration and severity assessed retrospectively were less with VIS + wIRA than with LED, irrespective of cooling. Conclusions, All treatments showed high efficacy with good cosmetic outcome and high patient satisfaction. Efficacy of treatment was better without spray cooling. VIS + wIRA PDT was less painful than LED PDT for PDT without spray cooling. [source] Pegylated liposomal doxorubicin-efficacy in patients with recurrent high-grade gliomaCANCER, Issue 6 2004Peter Hau M.D. Abstract BACKGROUND Doxorubicin exhibits high efficacy in malignant glioma cell cultures. Nonetheless, as a standard formulation, doxorubicin has not been used clinically, due to poor penetration of the blood-brain barrier. Furthermore, doxorubicin is known to induce tumor resistance genes. To address both of these issues, the authors investigated the use of pegylated liposomal doxorubicin (CaelyxÔ; Essex Pharma, Munich, Germany) alone (Trial 1) and in combination with tamoxifen (Trial 2) in two sequentially performed nonrandomized prospective Phase II trials involving patients with recurrent high-grade glioma. METHODS Twenty patients were included in each trial. Progression-free survival at 6 months (PFS-6) and toxicity were the primary endpoints. Expression of the tumor resistance proteins multidrug resistance protein 1 (MDR-1) and multiple resistance protein (MRP) was evaluated by immunohistochemical methods and by sestamibi,single-photon emission computed tomography (SPECT). RESULTS The overall response rate (including cases of disease stabilization) was 40% in both Trial 1 and Trial 2. PFS-6 was 15%, and the median time to disease progression was 17 weeks. It is noteworthy that 40% of patients with Grade III tumors had long-term responses, which lasted for up to 3 years. There was no significant difference between Trial 1 and Trial 2 in terms of efficacy. Both regimens were well tolerated, with the main side effect being palmoplantar erythrodysesthesia. The authors found no correlation between clinical response and expression of tumor resistance genes or between clinical response and SPECT data. CONCLUSIONS Pegylated liposomal doxorubicin administered alone or in combination with tamoxifen is safe and moderately effective in patients with recurrent high-grade glioma. None of the putative predictors for response that were evaluated proved to be significant in this setting. Cancer 2004. © 2004 American Cancer Society. [source] UR-3216: A Manageable Oral GPIIb/IIIa AntagonistCARDIOVASCULAR THERAPEUTICS, Issue 1 2001Kosuke Baba ABSTRACT UR-3216, a prodrug, is a novel, selective, and orally active platelet surface glycoprotein GPIIb/IIIa) receptor antagonist. The most important property of UR-3216 is the very tight binding of its active metabolite to platelets (Ki for resting platelets is <1 nM). UR-2992, the active form of UR-3216, binds to platelets for a long period of time, while the unbound drug is rapidly cleared. Therefore, after an initial loading dose of 0.1 mg/kg, only once daily repeated low maintenance doses of UR-3216 (<0.05 mg/kg p.o.) are required. This regimen maintains a high level of inhibition of platelet aggregation and, due to a small peak-to-trough ratio, severe bleeding is avoided. The therapy with UR-3216 is easy to manage, because it has low peak-to-trough ratio and high efficacy (>80% inhibition of platelet aggregation). In addition, UR-3216 does not produce excessive bleeding or thrombocytopenia and does not interact with abciximab. UR-3216 is excreted mostly in bile, so that it will not accumulate in patients with chronic renal dysfunction. UR-2316 has the following abciximab-like features: (a) its half-lives for residence on platelets, inhibition of platelets aggregation and bleeding time prolongation are 60 to 80 h, 24, and 2 h, respectively; (b) its receptor binding occupancy is similar to that of abciximab (Mab1 is inhibited and Mab2 is unaltered). In conclusion, UR-3216 is a promising, orally active GPIIb/IIIa antagonist for the treatment of cardiovascular diseases. [source] Gene Therapy in HIV-Infected Cells to Decrease Viral Impact by Using an Alternative Delivery MethodCHEMMEDCHEM, Issue 6 2010Teresa Gonzalo Dr. Abstract The ability of dendrimer 2G-[Si{O(CH2)2N(Me)2+(CH2)2NMe3+(I,)2}]8 (NN16) to transfect a wide range of cell types, as well as the possible biomedical application in direct or indirect inhibition of HIV replication, was investigated. Cells implicated in HIV infection such as primary peripheral blood mononuclear cells (PBMC) and immortalized suspension cells (lymphocytes), primary macrophages and dendritic cells, and immortalized adherent cells (astrocytes and trophoblasts) were analyzed. Dendrimer toxicity was evaluated by mitochondrial activity, cell membrane rupture, release of lactate dehydrogenase, erythrocyte hemolysis, and the effect on global gene expression profiles using whole-genome human microarrays. Cellular uptake of genetic material was determined using flow cytometry and confocal microscopy. Transfection efficiency and gene knockdown was investigated using dendrimer-delivered antisense oligonucleotides and small interfering RNA (siRNA). Very little cytotoxicity was detected in a variety of cells relevant to HIV infection and erythrocytes after NN16 dendrimer treatment. Imaging of cellular uptake showed high transfection efficiency of genetic material in all cells tested. Interestingly, NN16 further enhanced the reduction of HIV protein 24 antigen release by antisense oligonucleotides due to improved transfection efficiency. Finally, the dendrimer complexed with siRNA exhibited therapeutic potential by specifically inhibiting cyclooxygenase-2 gene expression in HIV-infected nervous system cells. NN16 dendrimers demonstrated the ability to transfect genetic material into a vast array of cells relevant to HIV pathology, combining high efficacy with low toxicity. These results suggest that NN16 dendrimers have the potential to be used as a versatile non-viral vector for gene therapy against HIV infection. [source] Pharmacological profile of the new antihistaminesCLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 1 2005J.-P. Tillement Summary The second-generation H1 antihistamines are a highly efficacious drug class in the treatment of allergic rhinitis (AR) and dermatitis, and distinct from the first-generation H1 antihistamines, predominantly because of their non-sedating nature at recommended dosages. Despite a marked chemical heterogeneity, the non-sedating H1 antihistamines have many similarities, in particular, high affinity for H1 receptors, high efficacy, anti-inflammatory effects, which may be independent of direct H1 -receptor function, and lack of central nervous system side-effects. Some studies have suggested that differences in the chemical structures of these compounds generally lead to differences in the pharmacokinetic properties, which determine their overall clinical usefulness. In particular, it has been demonstrated that there are differences in selectivity for H1 receptors, the apparent volume of distribution, metabolism and elimination and interaction with other drugs. A comparison of levocetirizine, fexofenadine, desloratadine and mizolastine (some of the most commonly prescribed drugs in the treatment of AR and dermatitis) has demonstrated that, unlike levocetirizine and fexofenadine, desloratadine and mizolastine can bind to muscarinic receptors and cardiac K+ channels, and therefore have both lower selectivity and the potential to induce muscarinic and serious cardiac side-effects. However, this is noted at higher than recommended doses. Similarly, desloratadine and mizolastine undergo extensive metabolism and, together with fexofenadine, have the potential to interact with other drugs, in turn increasing the potential for severe toxic effects. In contrast, levocetirizine is not metabolized, is eliminated rapidly from the body, does not demonstrate any significant drug interactions and has the lowest volume of distribution. These findings suggest that levocetirizine is likely to be a safer drug than fexofenadine, desloratadine and mizolastine. [source] | ||||||||||||||||||||||||||||||||||