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Efficacy Assessments (efficacy + assessment)
Selected AbstractsLocal application of n,3 or n,6 polyunsaturated fatty acids in the treatment of human experimental gingivitisJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 4 2002Jörg Eberhard Abstract Background: Polyunsaturated fatty acids have the potential to attenuate inflammation by the synthesis of mediators of the 15-lipoxygenase pathways, which show opposite effects to the pro-inflammatory arachidonic acid metabolites such as leukotriene B4 (LTB4). Aims: The aim of this clinical study was to evaluate the effects of topical application of n,6 or n,6 polyunsaturated fatty acids in patients with experimental gingivitis. Methods: In each subject, similar teeth served as experimental and control over a 21-day non-hygiene phase and a 9-day resolving phase. Efficacy assessment was based on the bleeding on probing frequency (BOP) and the gingivocrevicular fluid volume (GCF). GCF was determined by inserting a filter paper strip for 30 s and measurements were performed on a Periotron 8000. The LTB4 concentration was analyzed by reversed-phase high-pressure liquid chromatography. Results: After 21 days of plaque growth, the BOP, GCF and LTB4 levels were significantly increased in all groups, with no differences between the control and experimental side. Rinsing of an area with established gingivitis for a 9-day period significantly reduced the GCF in the n,6 group (71.9 (18.7) versus 47.4 (11.4) Periotron Units, median (inter quartile range)). Conclusion: The topical application of n,6 or n,6 fatty acids failed to inhibit the development of experimental gingivitis. Rinsing with n,6 fatty acids could reduce the level of GCF in established experimental gingivitis. Zusammenfassung Hintergrund: Vielfach ungesättigte Fettsäuren haben das Potential, die Entzündung durch die Synthese von Mediatoren des 15-Lipoxygenaseweges zu behindern. Dies zeigt Gegeneffekte zu den pro-inflammatorischen Arachnoidonsäuremetaboliten wie Leukotrien B4 (LTB4). Ziele: Das Ziel dieser klinischen Studie war die Überprüfung des Effektes einer topischen Applikation von n,3 oder n,6 vielfach ungesättigten Fettsäuren bie Patienten mit experimenteller Gingivitis. Methoden: Bei jeder Person dienten ähnliche Zähne als Experiment und Kontrollen über eine 21tägige Nichthygiene-Phase und einer 9tägigen Erholungsphase. Wirksamkeitsmessungen basierten auf der Häufigkeit von Provokationsblutung (BOP) und dem Volumen der gingivalen krevikulären Flüssigkeit (GCF). GCF wurde durch Einbringen von Filterpapierstreifen für 30 Sekunden bestimmt. Die Messungen wurden mit einen Periotron 8000 durchgeführt. Die LTB4 Konzentration wurde mit der Umkehrphasen-Hochdruck-Flüssigkeitschromatographie analysiert. Ergebnisse: Nach 21 Tagen des Plaquewachstums waren die Level für BOP, GCF und LTB4 in allen Gruppen signifikant erhöht, ohne Differenzen zwischen den Kontrollen und den experimentellen Flächen. Die Spülung eines Gebietes mit etablierter Gingivitis für eine 9tägige Periode reduzierte die GCF in der n,6 Gruppe signifikant (71.9 (18.7) versus 47.4 (11.4) Peritron-Einheiten, Median (Zwischenquartilstreuung)). Zusammenfassung: Die topische Applikation von n,3 oder n,6 Fettsäuren verhindert die Entwicklung einer experimentellen Gingivitis nicht. Die Spülung mit n,6 Fettsäure konnte den Level der GCF bei einer bestehenden experimentellen Gingivitis reduzieren. Résumé Origine: Les acides gras poly-insaturés ont le potentiel d'atténuer l'inflammation en synthétisant des médiateurs des voies de la lipoxygénase 15 qui montrent des effets opposés aux métabolites de l'acide arachidonique pro-inflammatoire comme la leucotriène B4 (LTB4). But: Le but de cette étude clinique a été d'évaluer les effets de l'application topique d'acide gras poly-insaturés n,3 ou n,6 chez des patients effectuant d'une gingivite expérimentale. Méthodes: Chez chaque sujet, des dents semblables ont servi de sites tests et contrôles durant une phase sans hygiène buccale de 21 jours et une phase de retour à la normale de 9 jours. L'efficacité a été mesurée sur base de la fréquence du saignement au sondage (BOP) et le volume de fluide gingivale (GCF). Le GCF a été déterminé en insérant des papiers filtres pendant 30 s et les mesures ont été lues à l'aide du Périotron 8000. La concentration de LTB4 a été analysée par chromotographie liquide à haute pression à phrase arrière. Résultats: Après 21 jours d'accumulation de plaque dentaire les niveaux de BOP, GCF et LTB4 ont augmenté significativement dans tous les groupes sans aucune différence entre les sites tests et contrôles. Le rinçage d'une zone avec gingivite établie durant une période de 9 journées diminuait les GCF dans le groupe n,6 (unités du Péritron 72 (médian 19) versus 47 (11)). Conclusion: L'application topique d'acide gras n,3 ou n,6 ne permettait pas d'inhiber le développement de la gingivite expérimentale. Le rinçage avec des acides gras n,6 pouvait réduire le niveau de GCF dans la gingivite expérimentale établie. [source] Helicobacter pylori and Early Duodenal Ulcer Status Post-Treatment: a ReviewHELICOBACTER, Issue 2 2001Joette M. Meyer Abstract Background. Data submitted to the FDA were reviewed to analyze the relationship between Helicobacter pylori infection and the incidence of early duodenal ulcers, within 6 weeks, following treatment. Materials and Methods. Retrospective analyzes were performed on data from three H. pylori development programs submitted to the FDA: ranitidine-bismuth-citrate (RBC), lansoprazole (L) and omeprazole (O). Efficacy assessments for the RBC, L and O programs were made at end of a 4-week treatment period, 4,6 weeks following the end of a 14-day treatment period, and 4 weeks following the end of a 4-week treatment period, respectively. Results. Overall, there was a 15%, 21% and 23% decrease in the number of patients in the RBC, L and O programs, respectively, with ulcers among H. pylori cleared/eradicated patients post-treatment compared with patients with persistent infection. Among patients who did not have cleared/eradicated H. pylori in the RBC and O programs, where antisecretory agents were continued beyond the antimicrobial treatment period, the number of ulcers was lower in the antisecretory plus antimicrobial subgroups compared with the antimicrobial alone subgroups (37% vs. 46% for RBC and 33% vs. 42% for O). Among patients with cleared/eradicated H. pylori, the number of patients with ulcers in the antimicrobial alone subgroups and antisecretory plus antimicrobial subgroups were similar within each program. Antimicrobials alone had significantly lower rates of ulcers among patients with cleared/eradicated H. pylori as compared with patients without clearance/eradication. Conclusions. The early incidence of duodenal ulcers is significantly decreased in patients with H. pylori clearance/eradication. [source] Efficacy and safety of on-demand tadalafil for the treatment of erectile dysfunction in South-East Asian menINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2006YING LU GUO Aim:, Tadalafil is an inhibitor of phosphodiesterase type 5 used for the treatment of erectile dysfunction (ED). The efficacy and safety of tadalafil have been evaluated extensively in Western populations. Our aim was to assess the efficacy and safety of on-demand tadalafil for the treatment of ED in South-East Asian men. Methods:, This was a randomized, double-blind, placebo-controlled study of men with mild to severe ED of various etiologies randomized to receive placebo (n = 122), tadalafil 10 mg (n = 120), or tadalafil 20 mg (n = 125), taken as needed (maximum once daily) for 12 weeks. Efficacy assessments included the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) diary, and a Global Assessment Question (GAQ). Results:, Men from China, Singapore, and the Philippines participated in this trial (n = 367). Compared with placebo, tadalafil significantly improved erectile dysfunction on all efficacy outcomes (P < 0.001). Patients receiving tadalafil 10 mg and 20 mg experienced a significant mean improvement of 8.1 and 8.7, respectively, in the IIEF Erectile Function (IIEF-EF) domain score from baseline (vs placebo 2.4, P < 0.001). In patients receiving tadalafil 10 mg and 20 mg, the mean per-patient success rate for intercourse attempts (SEP3) was 62% and 70%, respectively, compared with 32% for the placebo group (P < 0.001). Of patients who received tadalafil 10 mg and 20 mg, 81% and 86% reported improved erections at endpoint (GAQ) compared with 44% in the placebo group (P < 0.001). The most common adverse events reported by patients were headache, back pain, dyspepsia, and dizziness. Conclusions:, Tadalafil was an effective and well-tolerated treatment for South-East Asian men with ED. [source] Efficacy and safety of a new single-dose terbinafine 1% formulation in patients with tinea pedis (athlete's foot): a randomized, double-blind, placebo-controlled studyJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2006JP Ortonne Abstract Background, Tinea pedis is a common dermatophyte infection with frequent recurrences. Terbinafine (presently used as a 1-week topical treatment of tinea pedis) is now available in a novel topical solution (film-forming solution , FFS), developed to allow single application. Objectives, To demonstrate the efficacy and safety of terbinafine 1% FFS in a randomized, double-blind, placebo-controlled, phase III trial, and to determine relapse or re-infection rate of tinea pedis at 12 weeks. Patients/methods, Fifty-four centres (27 in France; 27 in Germany) enrolled 273 evaluable patients (2 : 1 randomization). Patients applied terbinafine 1% FFS or placebo only once between, under and over the toes, soles and sides of both feet. Efficacy assessments included direct microscopy, mycological culture, and clinical signs and symptoms at baseline, and at weeks 1, 6 and 12 after the single drug application. Results, Effective treatment (negative mycology plus absent/minimal symptoms) at week 6 in the terbinafine 1% FFS group was 63%; vehicle was 17% (P 0.0001). Mycological cure was 72% in the terbinafine group and 21% in the placebo (P 0.0001) at week 6. Clinical signs/symptoms decreased significantly in the active group compared to the placebo. The self-assessment of itching and burning sensation by the patient showed a clear reduction in symptoms starting 15 min after treatment application (this could be attributed to the cooling effect of the FFS). Recurrence (positive culture at 3 months) occurred in 12.5% of the effectively treated patients at week 6 in the terbinafine group. FFS was well tolerated. Conclusion, Terbinafine 1% FFS, single dose application is an effective, safe and convenient treatment for tinea pedis. The relapse/re-infection rate 3 months after the end of single-dose therapy is similar to that previously demonstrated in a study using terbinafine 1% cream for 7 days. [source] Long-term benefits of rivastigmine in dementia associated with Parkinson's disease: An active treatment extension studyMOVEMENT DISORDERS, Issue 4 2006Werner Poewe MD Abstract In patients with dementia associated with Parkinson's disease (PD), the efficacy and safety of rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, were previously demonstrated in a 24-week double-blind placebo-controlled trial. Our objective was to determine whether benefits were sustained over the long term. Following the double-blind trial, all patients were permitted to enter an active treatment extension study, during which they received rivastigmine 3,12 mg/day. Standard safety assessments were performed. Efficacy assessments included the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) and other measures of cognition, daily function, neuropsychiatric symptoms, and executive function. Of 433 patients who completed the double-blind trial, 334 entered and 273 completed the active treatment extension. At 48 weeks, the mean ADAS-cog score for the whole group improved by 2 points above baseline. Placebo patients switching to rivastigmine for the active treatment extension experienced a mean cognitive improvement similar to that of the original rivastigmine group during the double-blind trial. The adverse event profile was comparable to that seen in the double-blind trial. Long-term rivastigmine treatment appeared well tolerated and may provide sustained benefits in dementia associated with PD patients who remain on treatment for up to 48 weeks. © 2005 Movement Disorder Society [source] Efficacy and safety of once-daily fluticasone furoate nasal spray in children with seasonal allergic rhinitis treated for 2 wkPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 3 2009Eli O. Meltzer The objective of this study was to evaluate the efficacy and safety of fluticasone furoate (FF) nasal spray 55 and 110 ,g once daily in children with seasonal allergic rhinitis (SAR). Patients (n = 554) received placebo nasal spray or FF, administered using a unique side-actuated device, in a 2-wk, randomized, double-blind study. Symptoms were evaluated by patients using a 4-point categorical scale. Efficacy assessments included reflective and instantaneous total nasal symptom scores (r/iTNSS). Primary analyses were conducted in patients aged 6,11 yr in the intent-to-treat population (ITT); the 2,11 yr group provided supportive analyses. In patients aged 6,11 yr, FF 110 ,g once daily significantly improved the daily rTNSS compared with placebo. FF 55 ,g once daily was only numerically better for rTNSS and iTNSS. Secondary pre-dose iTNSS and overall response to therapy were significant with FF 110 ,g. The significant findings for FF 110 ,g were supported by analyses in the entire ITT population of 2,11 yr olds. Both doses of FF were well tolerated. These study results suggest that FF nasal spray administered once daily for 2 wk is well tolerated and effective for the treatment of SAR symptoms in children aged 2,11 yr. [source] Safety and efficacy of oral fexofenadine in children with seasonal allergic rhinitis , a pooled analysis of three studiesPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 3 2004Eli O. Meltzer Allergic rhinitis is one of the most common clinical conditions in children; however, data regarding the safety of antihistamines in children with seasonal allergic rhinitis are limiting. To evaluate the safety and efficacy of fexofenadine in children with seasonal allergic rhinitis, data were pooled from three, double-blind, randomized, placebo-controlled, parallel-group, 2-week trials in children (6,11 year) with seasonal allergic rhinitis. All studies assessed fexofenadine HCl 30 mg b.i.d.; two studies included fexofenadine HCl at 15 and 60 mg b.i.d. Patients (and investigators) reported any adverse events during the trial. Physical examinations, including measurements of vital signs and laboratory tests, were performed. Efficacy assessments (total symptom score and individual symptom scores) were evaluated. Exposure to fexofenadine HCl 30 mg b.i.d. and to any fexofenadine dose exceeded 10,000 and 17,000 patient days, respectively. Incidences of adverse events, and discontinuations because of adverse events, were low and similar across treatment groups. In the placebo group, 24.4% of subjects reported adverse events compared with 24.1% for fexofenadine HCl 30 mg b.i.d., and 28.4% for all fexofenadine-treated groups. The most common adverse event overall was headache (4.3% placebo; 5.8% fexofenadine HCl 30 mg b.i.d.; and 7.2% any fexofenadine doses). Treatment-related adverse events were similar across treatment groups with no sedative effects. Fexofenadine HCl 30 mg b.i.d. was significantly superior to placebo in reducing the total symptom score and all individual seasonal allergic rhinitis symptoms, including nasal congestion (p < 0.05). Fexofenadine, at doses of up to 60 mg b.i.d., is safe and non-sedating, and fexofenadine HCl 30 mg b.i.d. effectively reduces all seasonal allergic rhinitis symptoms in children aged 6,11 years. [source] Efficacy and Safety of On-Demand Oral Tadalafil in the Treatment of Men with Erectile Dysfunction in Taiwan: A Randomized, Double-Blind, Parallel, Placebo-Controlled Clinical StudyTHE JOURNAL OF SEXUAL MEDICINE, Issue 2 2004Kuang-Kuo Chen MD Conflict of Interest. Timothy M. Costigan and Jeffrey T. Emmick are employees of Eli Lilly, Indianapolis. ABSTRACT Introduction., Tadalafil is a phosphodiesterase type 5 inhibitor for the treatment of erectile dysfunction (ED). Past clinical trials have assessed its efficacy and safety in western populations. Tadalafil has not been investigated in a large clinical trial with a South-east Asian population. Aim., To assess the efficacy and safety of on-demand tadalafil for the treatment of ED in a 12-week, double-blind, placebo-controlled study in Taiwan. Methods., Men with mild to severe ED of various etiologies were randomized to receive placebo, tadalafil 10 mg, or tadalafil 20 mg, taken as needed (maximum once daily). Efficacy assessments included the International Index of Erectile Function, the Sexual Encounter Profile (SEP) diary, and a Global Assessment Question (GAQ). Results., Tadalafil significantly improved erectile function compared with placebo (P < 0.005, all measures). At endpoint, the patients receiving tadalafil reported a greater mean per-patient percentage of successful intercourse attempts (SEP question 3: 70.0%, 10 mg; 78.0%, 20 mg) than placebo-treated patients (42.8%) and a greater proportion of improved erections (GAQ: 92.3% and 84.6% vs. 54.5%). Most treatment-emergent adverse events were mild or moderate. The most common adverse events were back pain, dyspepsia, and myalgia. Conclusions., Tadalafil was an effective, well-tolerated therapy for men in Taiwan with ED of broad-spectrum severity and etiology. [source] Golimumab, a new human tumor necrosis factor , antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: Twenty-four,week efficacy and safety results of a randomized, placebo-controlled study,ARTHRITIS & RHEUMATISM, Issue 4 2009Arthur Kavanaugh Objective To assess the efficacy and safety of golimumab in patients with active psoriatic arthritis (PsA). Methods Adult patients with PsA who had at least 3 swollen and 3 tender joints and active psoriasis were randomly assigned to receive subcutaneous injections of placebo (n = 113), golimumab 50 mg (n = 146), or golimumab 100 mg (n = 146) every 4 weeks through week 20. Efficacy assessments through week 24 included the American College of Rheumatology 20% improvement criteria (ACR20), the Psoriasis Area and Severity Index (PASI) in patients in whom at least 3% of the body surface area was affected by psoriasis at baseline, the Short Form 36 Health Survey (SF-36), the disability index of the Health Assessment Questionnaire (HAQ), the Nail Psoriasis Severity Index (NAPSI), the physician's global assessment of psoriatic nail disease, and enthesitis (using the PsA-modified Maastricht Ankylosing Spondylitis Enthesitis Score [MASES] index). Results At week 14, 48% of all patients receiving golimumab, 51% of patients receiving golimumab 50 mg, and 45% of patients receiving golimumab 100 mg achieved an ACR20 response (the primary end point), compared with 9% of patients receiving placebo (P < 0.001 for all comparisons). Among the 74% of patients in whom at least 3% of the body surface area was affected by psoriasis at baseline, 40% of those in the golimumab 50 mg group and 58% of those in the golimumab 100 mg group had at least 75% improvement in the PASI at week 14 (major secondary end point), compared with 3% of placebo-treated patients (P < 0.001 for both doses). Significant improvement was observed for other major secondary end points (the HAQ and the SF-36), the NAPSI, the physician's global assessment of psoriatric nail disease, and the PsA-modified MASES index in each golimumab group compared with placebo. This efficacy was maintained through week 24. Golimumab was generally well tolerated. Conclusion Treatment with golimumab at doses of 50 mg and 100 mg significantly improved active PsA and associated skin and nail psoriasis through week 24. [source] Safety, tolerability and efficacy of a rapid dose escalation of quetiapine in bipolar I mania: the FATIMA studyACTA NEUROPSYCHIATRICA, Issue 3 2009Eric Constant Objective: The FATIMA study (FAst TItration of quetiapine fumarate in bipolar I MAnia) evaluated the safety, tolerability and efficacy of a rapid dose escalation of quetiapine in acutely ill bipolar I patients experiencing a manic episode. Methods: In an open-label, phase II pilot study, 29 patients aged 18 years or older, hospitalised with a bipolar I manic episode, received quetiapine twice daily for 21 days. Quetiapine was administered at 200, 400, 600, then 800 mg/day on the first 4 days, with flexible dosing (400,800 mg/day) subsequently. The primary endpoint was the proportion of patient dropouts because of adverse drug reactions during the first 7 days. Secondary safety assessments included incidences of adverse drug reactions and significant changes in vital signs. Efficacy assessments included Young Mania Rating Scale (YMRS) and Clinical Global Impressions Severity of Illness (CGI-S) score changes from day 1 to day 21. Results: Twenty patients (69%) completed the study. No patients withdrew as a result of drug-related adverse events (AEs) during the first 7 days. Twenty-three patients reported 58 adverse events, and most of the adverse events were mild or moderate. No clinically relevant abnormalities in vital signs were reported. Mean YMRS and CGI-S scores decreased significantly from baseline to day 21 (p < 0.001). Response and remission rates were 78 and 70%, respectively, at the end of the study. Conclusion: Rapid dose escalation of quetiapine to 800 mg/day over 4 days was well tolerated and effective in reducing symptoms within 5 days in acutely ill bipolar I patients with a manic episode. [source] Interictal Psychoses in Comparison with Schizophrenia,A Prospective StudyEPILEPSIA, Issue 12 2007Yukari Tadokoro Summary Purpose: To prospectively investigate the incidence of interictal psychoses of epilepsy patients, and make a comparison between those with interictal psychoses and patients with schizophrenia in respect to their responses to antipsychotic drugs, as well as psychotic states. Methods: We undertook a two-part prospective investigation. In Part I, the psychotic episodes of 619 epilepsy patients were investigated, while 182 patients with psychotic syndromes were followed in Part II, of whom 59 were diagnosed with schizophrenia and 13 with epilepsy with interictal psychoses. The Positive and Negative Syndrome Scale was used for efficacy assessment. Results: The average annual incidence of interictal psychosis was 0.42% during the 56-month study period. A significant difference was found between patients with schizophrenia and epilepsy patients with interictal psychoses in respect to results on the negative subscale of the PANSS at the initial examination (mean scores of 18.1 and 13.2, respectively, p = 0.004). The response rates one year later for these groups were 27.1% and 53.8%, respectively, which showed a trend of better response to the antipsychotic medication by the epilepsy group (p = 0.098). Initial and maximum doses of antipsychotic drugs used for epilepsy patients with interictal psychoses were significantly lower than those used for patients with schizophrenia (p = 0.008 and p = 0.006, respectively). Conclusions: Schizophrenia and epileptic psychosis showed different symptom profiles. On average, epilepsy patients with interictal psychoses achieved higher remission rates with lower doses of antipsychotic drugs as compared to patients with schizophrenia in the present 1-year follow-up study. [source] Assessment of visibility of facial wrinkle reduction by various types of observersINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 3 2004J. H. D. M. Westerink The prime objective of many facial wrinkle-reduction treatments is to achieve visible improvement. The visibility of before/after treatment differences is therefore often part of the efficacy assessment. This paper investigates whether the background knowledge of the people acting as observers in such assessments has an impact on the results, e.g., the subjects themselves are familiar with their faces, skin professionals have much experience in judging skin quality, and thus both might be more sensitive to small changes. In a clinical study, 44 female subjects were regularly treated during a period of 12 weeks with one of three wrinkle-reduction treatments: K, L and M (placebo). Photographs were taken before treatment and after 6 and 12 weeks. Three different types of observers judged the photographs: ,Observer type I: Twenty-four lay observers were given the 0- and 6-week and the 0- and 12-week pairs of photographs of all subjects to indicate the one with the least wrinkles in a two-alternative forced-choice procedure; ,Observer type II: The subjects themselves were given the 0- and 6-week and the 0- and 12-week pairs of their own photographs (eight replications) to indicate the photograph with the least wrinkles (two-alternative forced-choice); ,Observer type III: A trained panel of skin professionals (n = 3) each gave a 9-point Fitzpatrick wrinkle-severity score for all individual 0- and 12-week photographs. It was found that the lay observers perceived the same differences as the subjects themselves: significant improvements after 12 weeks for treatment K (P < 0.0005 and P = 0.005, respectively). No visible effects were seen for treatments L and M, but, most importantly, a significant difference between treatments K and M (placebo) (P = 0.015 and P = 0.01 for independent observers and the subjects themselves, respectively). The trained panel also identified this difference between K and M (P = 0.013) in favor of K, but here it was due to a significant deterioration over time of the ,placebo-treated' wrinkles (M, P = 0.03). Thus, in conclusion, no indications were found that extra knowledge , in the form of familiarity with the own face or in the form of professional training , results in the identification of more treatments that show significantly visible wrinkle reduction. [source] Atopic xerosis: employment of noninvasive biophysical instrumentation for the functional analyses of the mildly abnormal stratum corneum and for the efficacy assessment of skin care productsJOURNAL OF COSMETIC DERMATOLOGY, Issue 2 2006Hachiro Tagami MD Summary The subtle dryness of the skin surrounding the lesions of atopic dermatitis (AD) is called atopic dry skin or atopic xerosis (AX). AX is more susceptible to the development of AD skin lesions under various environmental stimuli than the clinically normal skin of the people who have or have had or will have AD, which might be called normal atopic skin (NAS) that shows no functional differences as compared to the skin of normal individuals. Routine histopathologic studies of AX that involve the invasive procedures of biopsy are not so helpful in clarifying the underlying pathogenesis. Modern, noninvasive biophysical instrumentation provides rich and quantitative information about various functional aspects of skin. The stratum corneum (SC) of AX reveals not only decreased hydration but also mildly impaired barrier function demonstrable as an increase in transepidermal water loss, elevated pH values, and an increased turnover rate of the SC consisting of thick layers of smaller-sized corneocytes. These data suggest that AX is related to mildly increased epidermal proliferation as a result of the presence of subclinical cutaneous inflammation. Although AX skin does not display any impairment in the recovery of barrier function after physical skin irritation by tape-stripping, it produces a much more severe, long-lasting inflammatory response together with a delay in barrier repair after chemical irritation such as that induced by sodium lauryl sulphate. The SC of AX is biochemically characterized by reduction in the amounts of ceramides, especially ceramide I, sebum lipids, and water-soluble amino acids. None of these changes in SC functions are seen in NAS, which includes not only the normal-looking skin of AD patients long after regression of all active lesions but also of latent atopic skin such as neonates who later develop AD. This suggests that all of the observed functional as well as biochemical abnormalities of AX are a reflection of subclinical inflammation. The presence of the underlying inflammation in AX also differentiates it from senile xerosis. The mildly impaired SC functions of AX can be improved by daily repeated applications of effective moisturizers, i.e., corneotherapy, which is effective in preventing the exacerbating progression of AX to AD resulting from inadvertent scratching of the skin that facilitates the penetration of environmental allergens into the skin. The biophysical confirmation of such efficacy of moisturizers, including cosmetic bases on the mildly impaired barrier function and decreased water-holding capacity of the SC of AX, definitely substantiates the importance of skin care for the cosmetic skin problems that affect every individual in the cold and dry season ranging from late autumn to early spring. [source] Importance of specimen type in detecting human papillomavirus DNA from the female genital tractJOURNAL OF MEDICAL VIROLOGY, Issue 9 2009Christine C. Roberts Abstract HPV testing is a valuable tool in cervical cancer screening and efficacy assessment of HPV vaccines. Concordance of specimens from three sites for detection of HPV DNA in the female genital tract was evaluated. At a single visit, the following specimens were collected: an endo-ecto-cervical swab (EEC), labial/vulvar/perineal/perianal swab (LVPP) and cervicovaginal lavage (CVL). Specimens were evaluated with HPV6, HPV11, HPV16, and HPV18 type- and gene-specific PCR assays. Of the 898 women evaluated at baseline, 232 were HPV PCR positive in at least one specimen. Of these, for HPV6, HPV11, HPV16, and HPV18, respectively, throughout: (a) 70.4%, 40.0%, 65.3%, and 64.1% tested three-site positive; (b) 13.6%, 30.0%, 19.7%, and 18.8% tested two-site positive; and (c) 16.4%, 30.0%, 15.0%, and 17.2% tested single-site positive. For patients who tested single-site positive for HPV6, HPV11, HPV16, or HPV18, respectively, the specimen was: LVPP in 92.3%, 33.3%, 68.2%, and 72.7%; EEC in 0.0%, 33.3%, 18.2%, and 9.1%; and CVL in 7.7%, 33.3%, 13.6%, and 18.2%. Combining results of swab specimens together increases detection of HPV6, HPV11, HPV16, and HPV 18, respectively, to 98.7%, 90.0%, 97.9%, and 96.9%. HPV DNA is detectable from all three sites using type-specific PCR assays; most women who tested positive for a given HPV type were positive for that type in all three specimens. J. Med. Virol. 81:1620,1626, 2009. © 2009 Wiley-Liss, Inc. [source] Rapid production of a plasmid DNA encoding a malaria vaccine candidate via amino-functionalized poly(GMA- co -EDMA) monolithAICHE JOURNAL, Issue 11 2008Michael K. Danquah Abstract Malaria is a global health problem; an effective vaccine is urgently needed. Due to the relative poverty and lack of infrastructure in malaria endemic areas, DNA-based vaccines that are stable at ambient temperatures and easy to formulate have great potential. While attention has been focused mainly on antigen selection, vector design and efficacy assessment, the development of a rapid and commercially viable process to manufacture DNA is generally overlooked. We report here a continuous purification technique employing an optimized stationary adsorbent to allow high-vaccine recovery, low-processing time, and, hence, high-productivity. A 40.0 mL monolithic stationary phase was synthesized and functionalized with amino groups from 2-Chloro-N,N-diethylethylamine hydrochloride for anion-exchange isolation of a plasmid DNA (pDNA) that encodes a malaria vaccine candidate, VR1020-PyMSP4/5. Physical characterization of the monolithic polymer showed a macroporous material with a modal pore diameter of 750 nm. The final vaccine product isolated after 3 min elution was homogeneous supercoiled plasmid with gDNA, RNA and protein levels in keeping with clinical regulatory standards. Toxicological studies of the pVR1020-PyMSP4/5 showed a minimum endotoxin level of 0.28 EU/mg pDNA. This cost-effective technique is cGMP compatible and highly scalable for the production of DNA-based vaccines in commercial quantities, when such vaccines prove to be effective against malaria. © 2008 American Institute of Chemical Engineers AIChE J, 2008 [source] A randomized, multicentre, open-label, parallel-group trial to compare the efficacy and safety profile of daming capsule in patients with hypercholesterolemiaPHYTOTHERAPY RESEARCH, Issue 7 2009Ai Jing Abstract To study the efficacy and tolerability of Daming capsule (DMC) in Chinese patients with hyperlipidemia, a randomized, multi-centre, open-label, parallel-group trial was conducted. Sixty enrolled patients with hyperlipidemia allocated to six medical centers were randomly divided into two groups of 30 individuals each. One group received DMC 2 g b.i.d. for 6 weeks, and the other received pravastatin 10 mg o.d. for 6 weeks. For efficacy assessment, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were measured before and after drug treatment. Serum TC and LDL-C levels in the DMC-treatment group were significantly decreased compared with those before treatment (p < 0.05), while TG and HDL-C levels did not change much. Tolerability was assessed by heart rate (HR), blood pressure (BP), body mass index (BMI), alanine aminotransferase (ALT) and creatinine (Cr), which were not changed in either the DMC or pravastatin groups at 3 and 6 weeks (p > 0.05). Besides, eight patients experienced diarrhea during DMC treatment and two experienced myalgia and epigastric discomfort during pravastatin treatment. Based on the above results, it was concluded that DMC may be a good candidate for the treatment of hyperlipidemia and further clinical trials are warranted. Copyright © 2009 John Wiley & Sons, Ltd. [source] Agreement of efficacy assessments for five-grass pollen sublingual tablet immunotherapyALLERGY, Issue 1 2009A. Didier Background:, The optimal dose of five-grass pollen sublingual tablet immunotherapy (SLIT) was established recently by the primary criteria Rhinoconjunctivitis Total Symptom Score (RTSS) from the first treatment season. Secondary and exploratory criteria, such as RTSS at peak pollen season, exploratory combined symptom and rescue medication use score, quality of life and immunological markers are calculated and described in this analysis. Methods:, Six hundred and twenty-eight patients with grass pollen rhinoconjunctivitis (,2 years duration) were randomized in a double-blind, placebo-controlled trial conducted in Europe. Patients received once-daily SLIT (Stallergenes, Antony, France) of 100IR, 300IR, 500IR or placebo, starting 4 months before grass pollen season and throughout the 2005 season. Patients were instructed to take rescue medication only if symptoms were severe and record symptom severity on using the RTSS. Results:, Both 300IR and 500IR doses significantly reduced mean RTSS at pollen peak (P = 0.0005 and P = 0.0014, respectively) and the exploratory combined score (P = 0.0001 and P = 0.0026, respectively) compared with placebo. Compared with patients in the placebo group, those who were taking the 300IR and 500IR doses reported significantly improved quality of life using the mean Rhinoconjunctivitis Quality of Life Questionnaire scores during the peak of the pollen season (P < 0.0001) and at the end of the pollen season (P = 0.0031 and P , 0.0001, respectively). Specific immunoglobulin G4 increased significantly depending on the SLIT dose (P < 0.0001). Conclusions:, All secondary efficacy criteria, including efficacy at pollen peak, combined score, quality of life and immunological changes, indicate that 300IR tablets represent the optimal dose and suggest it is appropriate for use in clinical practice. [source] Disease remission and sustained halting of radiographic progression with combination etanercept and methotrexate in patients with rheumatoid arthritis,ARTHRITIS & RHEUMATISM, Issue 12 2007D. van der Heijde Objective The Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO) is a 3-year, double-blind, multicenter study evaluating the efficacy and safety of etanercept, methotrexate, and the combination of etanercept plus methotrexate in patients with active rheumatoid arthritis (RA). The results after 1 and 2 years of the study have been previously reported. Here we provide the 3-year clinical and radiographic outcomes and safety of etanercept, methotrexate, and the combination in patients with RA. Methods In this randomized, double-blind, multicenter TEMPO study, 682 patients received etanercept 25 mg twice weekly, methotrexate ,20 mg weekly, or the combination. Key efficacy assessments included the Disease Activity Score (DAS) and the DAS in 28 joints. Results Combination therapy resulted in significantly greater improvement in the DAS and in more patients with disease in remission than either monotherapy. This finding was confirmed by longitudinal analysis; patients receiving combination therapy were more than twice as likely to have disease in remission than those receiving either monotherapy. Independent predictors of remission included male sex, lower disease activity, lower level of joint destruction, and/or better physical function. Combination and etanercept therapy both resulted in significantly less radiographic progression than did methotrexate (P < 0.05). Etanercept and combination treatment were well tolerated, with no new safety findings. Conclusion Etanercept plus methotrexate showed sustained efficacy through 3 years and remained more effective than either monotherapy, even after adjustment for patient withdrawal. Combination therapy for 3 years led to disease remission and inhibition of radiographic progression, 2 key goals for treatment of patients with RA. [source] | |||||||||||||||||||||||||