Phase III (phase + iii)

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Distribution within Medical Sciences

Terms modified by Phase III

  • phase iii clinical trial
  • phase iii clinical trials
  • phase iii studies
  • phase iii study
  • phase iii trial
  • phase iii trials

  • Selected Abstracts


    Statistical behavior of complex cancer karyotypes

    GENES, CHROMOSOMES AND CANCER, Issue 4 2005
    Mattias Höglund
    Epithelial tumors commonly show complex and variable karyotypes that obscure the identification of general patterns of the karyotypic evolution. To overcome some of these problems, we previously systematically analyzed the accumulated cytogenetic data from individual tumor types by using various statistical means. In the present study, we compare previous results obtained for nine tumor types and perform several meta-analyses of data obtained from a number of epithelial tumors, including head and neck, kidney, bladder, breast, colorectal, ovarian, and lung cancer, as well as from malignant melanoma and Wilms tumor, with the specific aim of discovering common patterns of karyotypic evolution. We show that these tumors frequently develop through a hypo- or a hyperdiploid pathway and progress by an increasing number of alternative imbalances through at least two karyotypic phases, Phases I and II, and possibly through a third, Phase III. During Phase I, the karyotypes exhibited a power law distribution of both the number of changes per tumor and the frequency distribution at which bands were involved in breaks. At the transition from Phase I to Phase II/III, the observed power law distributions were lost, indicating a transition from an ordered and highly structured process to a disordered and chaotic pattern. The change in karyotypic orderliness at the transition from Phase I to Phase II/III was also shown by a drastic difference in karyotypic entropy. © 2005 Wiley-Liss, Inc. [source]


    Adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis: Efficacy and safety results from a Phase II/III randomized controlled study

    THE JOURNAL OF DERMATOLOGY, Issue 4 2010
    Akihiko ASAHINA
    Abstract Incidence of psoriasis vulgaris in Asians is estimated at 0.05,0.3%. Studies in North America and Europe demonstrated that adalimumab, a fully human, recombinant, immunoglobulin G1 monoclonal antibody, was efficacious and well-tolerated in patients with chronic plaque psoriasis. This 24-week, placebo-controlled study evaluated the efficacy and safety of three different dosing regimens of adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis (n = 169). Patients were randomized to receive adalimumab 40 mg every other week (eow), adalimumab 80-mg loading dose at week 0 followed by adalimumab 40 mg eow starting at week 2, adalimumab 80 mg eow, or placebo eow given as s.c. injections. The primary efficacy endpoint was the percentage of patients achieving a 75% or greater improvement in Psoriasis Area and Severity Index (PASI 75) score at week 16. At week 16, PASI 75 response rates were significantly greater for all three adalimumab groups (40 mg eow: 57.9%, P < 0.001; 40 mg eow plus loading dose: 62.8%, P < 0.001; 80 mg eow: 81.0%, P < 0.001) versus placebo (4.3%). As early as week 4, the 40-mg eow plus loading dose and 80-mg eow groups achieved significantly greater PASI 75 response rates compared with placebo. Injection-site reactions and hepatic events occurred in greater percentages of adalimumab-treated patients compared with placebo. Adalimumab therapy demonstrated efficacy and safety at all three dosage regimens. Rapid response rate in patients receiving 40 mg eow plus loading dose supports using an 80-mg loading dose in the treatment of psoriasis. [source]


    Indirect evidence for increased mechanosensitivity of jejunal secretomotor neurones in patients with idiopathic bile acid malabsorption

    ACTA PHYSIOLOGICA, Issue 2 2009
    A. Bajor
    Abstract Aim:, The interdigestive motor rhythm, the migrating motor complex (MMC), is accompanied by active secretion of chloride during periods of distally propagating maximal motor activity (MMC phase III). We studied the behaviour of this system in bile acid malabsorption (BAM), a relative common cause of chronic diarrhoea. We measured motor activity and transmucosal potential difference (PD, reflecting active chloride secretion), in the proximal jejunum in healthy controls (n = 18) and in a group of patients with BAM (n = 11). The phase III-generated voltage was related to the degree of BAM quantified by the 75SeHCAT test. Methods:, We used a multi-channel intestinal infusion system to simultaneously measure jejunal pressure and PD. Saline passing calomel half-cells was infused into the jejunum and subcutaneously. Pressure and PD were recorded in the fasting state and after a test meal. Results:, In the absence of motor activity, jejunal PD was not significantly different from zero in either group. During MMC phase III, PD reached significantly higher mean and peak levels in BAM patients. The product of MMC phase III length multiplied by voltage, over 3 h, was also significantly higher in BAM patients (controls: median 307 mV × cm, range 70,398; BAM: median 511, range 274,2271, P < 0.01). This value was also significantly correlated with the degree of BAM as reflected by the 75SeHCAT test (P < 0.05). Conclusion:, Phase III induced jejunal secretion may be upregulated in BAM patients, resulting in overload of colonic reabsorption capacity. [source]


    ADAPTATION AND SPECIES RANGE

    EVOLUTION, Issue 2 2004
    Joel R. Peck
    Abstract Phase III of Sewall Wright's shifting-balance process involves the spread of a superior genotype throughout a structured population. However, a number of authors have suggested that this sort of adaptive change is unlikely under biologically plausible conditions. We studied relevant mathematical models, and the results suggest that the concerns about phase III of the shifting-balance process are justified, but only if environmental conditions are stable. If environmental conditions change in a way that alters species range, then phase III can be effective, leading to an enhancement of adaptedness throughout a structured population. [source]


    Do phytoplankton communities correctly track trophic changes?

    FRESHWATER BIOLOGY, Issue 10 2005
    An assessment using directly measured, palaeolimnological data
    Summary 1. Measurements of total phosphorus (TP) concentrations since 1975 and a 50-year time series of phytoplankton biovolume and species composition from Lake Mondsee (Austria) were combined with palaeolimnological information on diatom composition and reconstructed TP-levels to describe the response of phytoplankton communities to changing nutrient conditions. 2. Four phases were identified in the long-term record. Phase I was the pre-eutrophication period characterised by TP-levels of about 6 ,g L,1 and diatom dominance. Phase II began in 1966 with an increase in TP concentration followed by the invasion of Planktothrix rubescens in 1968, characterising mesotrophic conditions. Phase III, from 1976 to 1979, had the highest annual mean TP concentrations (up to 36 ,g L,1) and phytoplankton biovolumes (3.57 mm3 L,1), although reductions in external nutrient loading started in 1974. Phases II and III saw an expansion of species characteristic of higher nutrient levels as reflected in the diatom stratigraphy. Oligotrophication (phase IV) began in 1980 when annual average TP concentration, Secchi depth and algal biovolume began to decline, accompanied by increasing concentrations of soluble reactive silica. 3. The period from 1981 to 1986 was characterised by asynchronous trends. Annual mean and maximum total phytoplankton biovolume initially continued to increase after TP concentration began to decline. Reductions in phytoplankton biovolume were delayed by about 5 years. Several phytoplankton species differed in the timing of their responses to changing nutrient conditions. For example, while P. rubescens declined concomitantly with the decline in TP concentration, other species indicative of higher phosphorus concentrations, such as Tabellaria flocculosa var. asterionelloides, tended to increase further. 4. These data therefore do not support the hypotheses that a reduction in TP concentration is accompanied by (i) an immediate decline in total phytoplankton biovolume and (ii) persistence of the species composition characterising the phytoplankton community before nutrient reduction. [source]


    Statistical behavior of complex cancer karyotypes

    GENES, CHROMOSOMES AND CANCER, Issue 4 2005
    Mattias Höglund
    Epithelial tumors commonly show complex and variable karyotypes that obscure the identification of general patterns of the karyotypic evolution. To overcome some of these problems, we previously systematically analyzed the accumulated cytogenetic data from individual tumor types by using various statistical means. In the present study, we compare previous results obtained for nine tumor types and perform several meta-analyses of data obtained from a number of epithelial tumors, including head and neck, kidney, bladder, breast, colorectal, ovarian, and lung cancer, as well as from malignant melanoma and Wilms tumor, with the specific aim of discovering common patterns of karyotypic evolution. We show that these tumors frequently develop through a hypo- or a hyperdiploid pathway and progress by an increasing number of alternative imbalances through at least two karyotypic phases, Phases I and II, and possibly through a third, Phase III. During Phase I, the karyotypes exhibited a power law distribution of both the number of changes per tumor and the frequency distribution at which bands were involved in breaks. At the transition from Phase I to Phase II/III, the observed power law distributions were lost, indicating a transition from an ordered and highly structured process to a disordered and chaotic pattern. The change in karyotypic orderliness at the transition from Phase I to Phase II/III was also shown by a drastic difference in karyotypic entropy. © 2005 Wiley-Liss, Inc. [source]


    Tectono-sedimentary evolution of the northernmost margin of the NE German Basin between uppermost Carboniferous and Late Permian (Rotliegend)

    GEOLOGICAL JOURNAL, Issue 1 2001
    H. Rieke
    Abstract The tectono-sedimentary evolution of the Rotliegend deposits of the northernmost margin of NE German Basin (NEGB) has been analysed on the basis of detailed sedimentary logs of 300,m of core material together with the re-evaluation of 600,km of seismic lines. Three distinct phases were recognized. During the initial Phase I, basin geometry was largely controlled by normal faulting related to deep-seated ductile shearing leading to a strong asymmetric shape, with a steep fault-controlled eastern margin and a gently, dipping western margin. The results of forward modelling along a cross-section fit the basin geometry in width and depth and reveal a footwall uplift of c. 1000,m. Adjacent to the steep faults, local sedimentation of Lithofacies Type I was confined to non-cohesive debris flow-dominated alluvial fans, whereas the gently dipping western margin was dominated by alluvial-cone sedimentation. During the post-extensional period (Phase II), cooling of the lithosphere generated additional accommodation space. The sediments of Lithofacies Type II, comprising mainly clast-supported conglomerates, are interpreted as braided ephemeral stream flow-surge deposits. Tectonic quiescence and an increase in flood events resulting from wetter climate led to progradation of this facies over the entire region. At the end of this period, the accommodation space was almost completely filled resulting in a level topography. Phase III was controlled by the thermal-induced subsidence of the southerly located NEGB in post-Illawarra times. The formerly isolated region tilted towards the SW, thus forming the northern margin of the NEGB during uppermost Havel and Elbe Subgroup times. The sediments of Lithofacies Type III were divided into a marginal sandstone-dominated environment and a finer-grained facies towards the SW. The former consists of poorly-sorted coarse-grained sandstones of a proximal and medial ephemeral stream floodplain facies. The latter comprise mud flat fines and fine-grained distal ephemeral stream deposits. The end of the tectono-sedimentary evolution is marked by the basinwide Zechstein transgression. Copyright © 2001 John Wiley & Sons, Ltd. [source]


    Spending on new drug development,

    HEALTH ECONOMICS, Issue 2 2010
    Christopher Paul Adams
    Abstract This paper replicates DiMasi et al. (J. Health Econ. 2003; 22: 151,185; Drug Inf. J. 2004; 38: 211,223) estimates of expenditure on new drug development using publicly available data. The paper estimates that average expenditure on drugs in human clinical trials is around $27m per year, with $17m per year on drugs in Phase I, $34m on drugs in Phase II and $27m per year on drugs in Phase III of the human clinical trials. The paper's estimated expenditure on new drug development is somewhat greater than suggested by the survey results presented in DiMasi et al. (J. Health Econ. 2003; 22: 151,185; Drug Inf. J. 2004; 38: 211,223). The paper combines a 12-year panel of research and development expenditure for 183 publicly traded firms in the pharmaceutical industry with panel of drugs in human clinical trials for each firm over the same period. The paper estimates drug expenditure by estimating the relationship between research and development expenditure and the number of drugs in development for 1682 company/years (183 firms multiplied by the number of years for which we have financial and drug development information). The paper also estimates expenditure on drugs in various therapeutic categories. Copyright © 2009 John Wiley & Sons, Ltd. [source]


    Safety and tolerability of once-daily extended release quetiapine fumarate in acute schizophrenia: pooled data from randomised, double-blind, placebo-controlled studies

    HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2010
    Didier Meulien
    Abstract Introduction Extended release quetiapine fumarate (quetiapine XR) is a new formulation that allows once-daily dosing and a titration regimen that is simpler than that of immediate release quetiapine (quetiapine IR) and may potentially increase patients' adherence to their prescribed medication. Methods The tolerability of quetiapine XR was examined in an analysis of pooled data from three Phase III, double-blind, placebo-controlled, randomised studies with quetiapine IR as a reference treatment. Results The overall incidence of adverse events (AEs) was similar for quetiapine XR (69.5%) and quetiapine IR (72.5%). Most AEs were mild to moderate in severity and in line with those observed with quetiapine IR. The more rapid dose titration of quetiapine XR did not produce any new safety concerns and was as well tolerated as the regimen for quetiapine IR. Conclusions The results of this pooled analysis show that quetiapine XR administered once daily is generally as well tolerated as quetiapine IR given twice daily. These data, together with the simpler dose-titration of quetiapine XR that allowed therapeutically effective doses to be reached by Day 2, suggest that this formulation potentially may improve adherence in patients with schizophrenia. Copyright © 2010 John Wiley & Sons, Ltd. [source]


    Further testing of the Integrated Hydrology Model (InHM): event-based simulations for a small rangeland catchment located near Chickasha, Oklahoma

    HYDROLOGICAL PROCESSES, Issue 7 2005
    Keith Loague
    In the paper that is the foundation for this study, VanderKwaak and Loague (2001. Water Resources Research37: 999,1013) reported a demonstration of a fully coupled comprehensive physics-based hydrologic-response model, InHM (Integrated Hydrology Model), for two rainfall-runoff events from the small rangeland catchment known as R-5. The InHM simulations reported herein address (in three phases) limitations in the VanderKwaak and Loague (2001. Water Resources Research37: 999,1013) simulations. In Phase I, a new finite-element mesh was selected to represent R-5. In Phase II, with the new mesh in place, evaporation was considered for the R-5 events. In Phase III, with the new mesh in place and evaporation considered, the geology of R-5 was approximated. Each phase, compared with the results reported by VanderKwaak and Loague (2001. Water Resources Research37: 999,1013), shows a change in the simulated near-surface response. The performance of InHM for 15 R-5 events is also reported herein. The results from two stages of model calibration are presented. The uncertainty in initial soil-water content estimates for event-based simulation is shown to be a major limitation for physics-based models. The performance of InHM, relative to past event-based simulation efforts with a quasi-physically based rainfall-runoff model, is better for both peak stormflow and the time to peak stormflow, but worse for stormflow depth. The InHM simulations reported here set the stage for continuous simulation of near-surface response for the R-5 catchment with InHM. Copyright © 2004 John Wiley & Sons, Ltd. [source]


    Development of Geriatric Competencies for Emergency Medicine Residents Using an Expert Consensus Process

    ACADEMIC EMERGENCY MEDICINE, Issue 3 2010
    Teresita M. Hogan MD
    Abstract Background:, The emergency department (ED) visit rate for older patients exceeds that of all age groups other than infants. The aging population will increase elder ED patient utilization to 35% to 60% of all visits. Older patients can have complex clinical presentations and be resource-intensive. Evidence indicates that emergency physicians fail to provide consistent high-quality care for elder ED patients, resulting in poor clinical outcomes. Objectives:, The objective was to develop a consensus document, "Geriatric Competencies for Emergency Medicine Residents," by identified experts. This is a minimum set of behaviorally based performance standards that all residents should be able to demonstrate by completion of their residency training. Methods:, This consensus-based process utilized an inductive, qualitative, multiphase method to determine the minimum geriatric competencies needed by emergency medicine (EM) residents. Assessments of face validity and reliability were used throughout the project. Results:, In Phase I, participants (n = 363) identified 12 domains and 300 potential competencies. In Phase II, an expert panel (n = 24) clustered the Phase I responses, resulting in eight domains and 72 competencies. In Phase III, the expert panel reduced the competencies to 26. In Phase IV, analysis of face validity and reliability yielded a 100% consensus for eight domains and 26 competencies. The domains identified were atypical presentation of disease; trauma, including falls; cognitive and behavioral disorders; emergent intervention modifications; medication management; transitions of care; pain management and palliative care; and effect of comorbid conditions. Conclusions:, The Geriatric Competencies for EM Residents is a consensus document that can form the basis for EM residency curricula and assessment to meet the demands of our aging population. ACADEMIC EMERGENCY MEDICINE 2010; 17:316,324 © 2010 by the Society for Academic Emergency Medicine [source]


    The CONSORT statement checklist in allergen-specific immunotherapy: a GA2LEN paper

    ALLERGY, Issue 12 2009
    P. J. Bousquet
    The methodology of randomized clinical trials is essential for the critical assessment and registration of therapeutic interventions. The CONSORT (Consolidated Standards of Reporting Trials) statement was developed to alleviate the problems arising from the inadequate reporting of randomized controlled trials. The present article reflects on the items that we believe should be included in the CONSORT checklist in the context of conducting and reporting trials in allergen-specific immunotherapy. Only randomized, blinded (in particular blinding of patients, health care providers, and outcome assessors), placebo-controlled Phase III studies in this article. Our analysis focuses on the definition of patients' inclusion and exclusion criteria, allergen standardization, primary, secondary and exploratory outcomes, reporting of adverse events and analysis. [source]


    Omalizumab (Xolair) in children with seasonal allergic rhinitis: Leukotriene release as a potential in vitro parameter to monitor therapeutic effects

    PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 6 2007
    Matthias Volkmar Kopp
    To investigate the effect of omalizumab, a humanized monoclonal antibody, in addition to specific immunotherapy (SIT) on in vitro sulfidoleukotriene release (SLT) (A) before, (B) directly after, and (C) 1 yr after treatment with omalizumab. Children and adolescents (6.3,17.6 yr) with sensitization to birch and grass pollens and suffering from seasonal allergic rhinitis were included in a Phase III, placebo-controlled, multicenter clinical study. Within the four-arm study, patients were randomly chosen to receive SIT for either birch or grass pollen and either subcutaneous omalizumab or placebo for 24 wk during the pollen season. Thereafter, omalizumab or placebo treatment ended, but SIT therapy continued. Blood samples were collected from 92 (A, B) and 78 children (C), respectively. Leukocytes were isolated and stimulated with grass and birch pollen allergens. In the supernatants, SLT (LTC4, LTD4, LTE4) were measured using ELISA [cellular allergen stimulation test, DPC-Biermann, Germany]. At the end of treatment the combination of omalizumab + SIT-grass [median SLT-release: 2125 (before) and 416 ng/ml (after omalizumab treatment); p < 0.001] as well as omalizumab + SIT-birch [1404 and 207 ng/ml; p < 0.001] resulted in significantly lower SLT release after stimulation with the corresponding allergen compared to placebo + SIT-grass [2231 and 2490 ng/ml] or placebo + SIT-birch [1324 and 2489 ng/ml]. One year after omalizumab or placebo treatment, there was no significant difference in SLT release between the 4 groups (omalizumab + SIT-grass: 2855; SIT-grass + placebo: 2543; omalizumab + SIT-birch: 2417; SIT-birch + placebo: 2573 ng/ml). These results strongly suggest that the observed effects of decreased SLT release after omalizumab treatment were attributable to the treatment with omalizumab, rather than to SIT therapy. [source]


    Structural phases of hexamethylenetetramine,pimelic acid (1/1): a unified description based on a stacking model

    ACTA CRYSTALLOGRAPHICA SECTION B, Issue 4 2003
    Gervais Chapuis
    The thermotropic phase diagram of 1:1 co-crystals of hexamethylenetetramine and pimelic acid (heptanedioic acid) is investigated. Three crystalline phases are identified at ambient pressure. Phase I is disordered, as revealed by diffuse rods in its diffraction pattern. When the temperature is lowered the diffuse streaks disappear in Phase II, but superstructure reflections emerge indicating an ordering process of the structure through a non-ferroic, or at least non-ferroelastic, phase transition. Phase II is mainly characterized by an unusual distribution of its reflection intensities. Phase III is reached through a ferroelastic phase transition that induces twinned domains. A model based on the stacking of an elementary layer is proposed with the aim of describing the structures in a unified framework. Depending on the value of the unique stacking parameter ,, each of the different structures observed can be reproduced by this model. Its validity is then tested by a series of simulations reproducing the main features of the diffraction patterns such as the diffuse scattering streaks, the occurrence of superstructure peaks at lower temperature and twinning. [source]


    AL01 PACIFIC ISLANDS PROJECT , PAST PRESENT AND FUTURE

    ANZ JOURNAL OF SURGERY, Issue 2007
    D. A. K. Watters
    The Pacific Islands Project began in 1995 and in its early years had a focus on providing specialist services that were not available in the 10 island nations visited. In 2002 Nauru was added and PIP Phase III will end its 9 month bridging/extension phase in September 2007. During the last 12 years Fiji School of Medicine has commenced a postgraduate medical training program in surgery similar to that has been in existence in PNG since 1975. There are now a growing number of Pacific-trained surgeons who can select suitable cases, do some of the surgery, and supervise the postoperative care. Increasingly visiting teams have focused on transferring skills and building local capabilities (capacity building). The RACS, the Project Director and the speciality coordinators have managed the first three phases of the project in Australia. Phase III had on-going evaluation by an internal RACS committee under the chairmanship of Professor Hamish Ewing. AusAid also externally reviewed the project late in 2006. That review was generally complimentary as to what has been achieved but also points to some new goals for the future. At the time of writing this abstract the future direction of PIP is yet to be decided and designed. This will be done mid 2007. However, it is to be hoped there will be a new program, focused on capacity building, that is managed in the Pacific and employs the skills of Pacific Island Specialists wherever possible. RACS is likely to continue to play an important role in sourcing visiting specialists, organising training positions, arranging courses. We have much expertise to offer but there is no longer any need for us to set the agendas. [source]


    PHYSICOCHEMICAL COMPOSITIONAL ANALYSIS OF CERAMICS: A CASE STUDY IN KENTING, TAIWAN,

    ARCHAEOMETRY, Issue 4 2006
    MAA-LING CHEN
    The composition of ceramics does not just reflect the component of some specific, unprocessed, geological, raw material source, but also certain forms of human behaviour involved in its manufacture. The purpose of this research project is to apply the acid-extraction chemical method, complemented by a thin-section petrographic study, to the compositional analyses of certain local ceramic collections (mainly from several sites in the southern Taiwan area). The results present the raw materials that the ceramic manufacturers of the two cultural traditions (O-laun-pi Phase II and Phase III,IV), which overlapped temporally, used. These materials came from the same sources, but the ceramics were manufactured in different ways. Particularly, the people of O-laun-pi Phase III,IV also procured certain materials from either local sources or from somewhere in eastern Taiwan to make their pots. The results also indicate that there might have been a variation in terms of their manufacture among sites of the same cultural tradition. [source]


    An evaluation of dermoscopy fluids and application techniques

    BRITISH JOURNAL OF DERMATOLOGY, Issue 1 2003
    A.J. Gewirtzman
    SummaryBackground Dermoscopy, a noninvasive technique used to help physicians better visualize pigmented skin lesions, is becoming widely used by dermatologists. Yet despite its popularity, to our knowledge basic aspects such as the best immersion fluid (IF) to use and proper procedures for applying the IF and dermatoscope have never been the subject of a systematic investigation. Objectives To determine the best techniques for application of IF and the dermatoscope; to discover which IF results in the least amount of air inclusions; to determine which IF provides the best image quality. Methods and materials This study was divided into three phases. Phase I examined several techniques of taking digital dermoscopic photographs in an attempt to eliminate air bubbles. Phase II tested seven IFs to analyse quantitatively the number of air inclusions for each IF. Phase III investigated these same IFs to judge the image quality for each. Results Phase I: in our hands, the best technique to apply an IF is to use an eyedropper and place the IF directly onto the skin in combination with a ,roll-on technique': the dermatoscope's edge is placed on the skin first and is then rotated until the glass plate lies flat against the skin. Phase II: the alcoholic IF resulted in the least amount of air bubble inclusions (70% ethanol, 90% isopropanol and alcoholic disinfectant), while liquid paraffin (a mineral oil) resulted in the most air bubbles. Phase III: dermoscopic structures were equally clear with alcohols and liquid paraffin, but slightly blurry with ultrasound gel and water. Conclusions Although 90% isopropanol performed slightly better in terms of air inclusions, we prefer to use 70% ethanol in most circumstances because it has the advantage of being odourless, unlike its counterpart. Additionally, ethanol will not stain clothing, does not crystallize on the dermatoscope, disinfects and evaporates immediately (does not need to be wiped off). For certain local considerations, such as dermoscopy on mucosa or the nail, we prefer to use ultrasound gel because it will not flow. [source]


    HER-2/neu expression as a predictor of response to neoadjuvant docetaxel in patients with operable breast carcinoma

    CANCER, Issue 11 2005
    Peter A. Learn M.D.
    Abstract BACKGROUND The use of biologic markers to predict response to neoadjuvant chemotherapy may permit tailoring regimens to achieve maximal tumor response. Taxanes have demonstrated excellent activity in breast carcinoma; however, tumor-specific factors that predict clinical response have not been characterized thoroughly. METHODS The authors performed a historic review evaluating the association of tumor prognostic factors and response to neoadjuvant cyclophosphamide and doxorubicin (AC) with or without docetaxel (D) (AC vs. AC+D) in 121 women who previously were enrolled in a Phase III, randomized, clinical trial. Using pretreatment biopsy materials, immunohistochemical studies were performed for estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, p53, and Ki-67. Outcome variables were pathologic complete response (pCR) and positive clinical response (cPOS), which was defined as a , 50% regression in clinical tumor size prior to surgery. RESULTS In a multivariate analysis that controlled for tumor size and lymph node status, improved cPOS rates were observed with the addition of docetaxel in women with HER-2/neu -negative tumors (81% vs. 51%; P < 0.05), yielding an adjusted odds ratio of 3.5 (95% confidence interval, 1.2,13.0) in favor of docetaxel. Women who had HER-2/neu -negative tumors appeared to have a lower response rate with AC alone compared with women who had HER-2/neu -positive tumors (51% vs. 75%; P = 0.06), but response rates were matched when docetaxel was added (81% vs. 78%; P = 0.99). ER, PR, p53, and Ki-67 results were not associated significantly with response rates. CONCLUSIONS HER-2/neu status may predict improved clinical response rates from the addition of docetaxel to anthracycline-based neoadjuvant chemotherapy. Docetaxel may "rescue" the response in women who have HER-2/neu -negative tumors to match that observed in women who have HER-2/neu -positive tumors treated with AC alone. Cancer 2005. © 2005 American Cancer Society. [source]


    Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion

    CANCER, Issue 1 2004
    Lee S. Rosen M.D.
    Abstract BACKGROUND Treatment with zoledronic acid (Zol) was compared with a dose of 90 mg of pamidronate (Pam) in breast carcinoma (BC) patients with at least 1 osteolytic lesion based on data from a Phase III, randomized trial. METHODS Overall, 1130 patients with breast carcinoma who had all types of bone metastases (osteolytic, mixed, or osteoblastic by radiology) were randomized to receive treatment with either 4 mg of Zol or 8 mg of Zol as a 15-minute infusion or 90 mg of Pam as a 2-hour infusion every 3,4 weeks for 12 months. A skeletal-related event (SRE) was defined as a pathologic fracture, spinal cord compression, radiotherapy, or surgery to bone. RESULTS Among all patients with BC, the proportion of those who had an SRE (primary endpoint) was comparable between treatment groups (43% of patients who received 4 mg of Zol vs. 45% of patients who received Pam). Among patients who had breast carcinoma with at least 1 osteolytic lesion (n = 528 patients), the proportion with an SRE was lower in the 4-mg Zol group compared with the Pam group (48% vs. 58%), but this did not reach statistical significance (P = 0.058). The time to first SRE was significantly longer in the 4-mg Zol group compared with the Pam group (median, 310 vs. 174 days; P = 0.013). Moreover, multiple-event analysis demonstrated significant further reductions in the risk of developing SREs over the reduction achieved with Pam (30% in the osteolytic subset [P = 0.010] and 20% for all patients with BC [P = 0.037]). CONCLUSIONS The current data indicate that treatment with 4 mg of Zol was more effective than 90 mg of Pam in reducing skeletal complications in a subset of patients with breast carcinoma who had at least 1 osteolytic lesion at study entry. Cancer 2004;100:36,43. © 2003 American Cancer Society. [source]


    Indirect evidence for increased mechanosensitivity of jejunal secretomotor neurones in patients with idiopathic bile acid malabsorption

    ACTA PHYSIOLOGICA, Issue 2 2009
    A. Bajor
    Abstract Aim:, The interdigestive motor rhythm, the migrating motor complex (MMC), is accompanied by active secretion of chloride during periods of distally propagating maximal motor activity (MMC phase III). We studied the behaviour of this system in bile acid malabsorption (BAM), a relative common cause of chronic diarrhoea. We measured motor activity and transmucosal potential difference (PD, reflecting active chloride secretion), in the proximal jejunum in healthy controls (n = 18) and in a group of patients with BAM (n = 11). The phase III-generated voltage was related to the degree of BAM quantified by the 75SeHCAT test. Methods:, We used a multi-channel intestinal infusion system to simultaneously measure jejunal pressure and PD. Saline passing calomel half-cells was infused into the jejunum and subcutaneously. Pressure and PD were recorded in the fasting state and after a test meal. Results:, In the absence of motor activity, jejunal PD was not significantly different from zero in either group. During MMC phase III, PD reached significantly higher mean and peak levels in BAM patients. The product of MMC phase III length multiplied by voltage, over 3 h, was also significantly higher in BAM patients (controls: median 307 mV × cm, range 70,398; BAM: median 511, range 274,2271, P < 0.01). This value was also significantly correlated with the degree of BAM as reflected by the 75SeHCAT test (P < 0.05). Conclusion:, Phase III induced jejunal secretion may be upregulated in BAM patients, resulting in overload of colonic reabsorption capacity. [source]


    Cell surface analysis of the lipid-discharging obligate hydrocarbonoclastic species of the genus Alcanivorax

    EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 6 2010
    Alvin Brian Lange
    Abstract This study presents novel information useful for addressing the question how species of the genus Alcanivorax discharge triacylglycerols (TAG) and/or wax esters (WE). The observed structures were referred as "blebs" according to Gauthier et al.1 to avoid confusion with other discharging phenomena. The cells were aerobically cultivated on solid media and not in liquid media to maintain the cells in the native state, and were investigated by transmission electron microscopic (TEM) and scanning electron microscopic (SEM) methods to document the surface structures of the cells. The phenomenon of lipid export could be allocated to three phases: phase I: protrusion formation of the cell membrane occurred; phase II: discharging progressed further with blebs becoming larger; and phase III: the blebs at the cell surface were separated from the cells. Using freeze-fracture micrographs by TEM, vesicle experiments and TLC, we have shown that the blebs contained TAGs and WEs. The results shown in this study will support further research to unravel the unknown discharging mechanism. In addition, the formation of an extensive extracellular matrix was observed by SEM. [source]


    ADAPTATION AND SPECIES RANGE

    EVOLUTION, Issue 2 2004
    Joel R. Peck
    Abstract Phase III of Sewall Wright's shifting-balance process involves the spread of a superior genotype throughout a structured population. However, a number of authors have suggested that this sort of adaptive change is unlikely under biologically plausible conditions. We studied relevant mathematical models, and the results suggest that the concerns about phase III of the shifting-balance process are justified, but only if environmental conditions are stable. If environmental conditions change in a way that alters species range, then phase III can be effective, leading to an enhancement of adaptedness throughout a structured population. [source]


    Intratumoral cisplatin/epinephrine gel in advanced head and neck cancer: A multicenter, randomized, double-blind, phase III study in North America,

    HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2003
    Dan J. Castro MD
    Abstract Background. The objective was to evaluate the efficacy and safety of a novel intratumoral cisplatin/epinephrine injectable gel (CDDP/epi gel) for local control and palliation of tumor-related symptoms in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Patients and Methods. Eighty-seven patients were randomly assigned to either CDDP/epi or placebo gel in this phase III, double-blind study. Tumors were ,20 cm3; most recurrences (88%) were in a previously irradiated field. The most symptomatic or threatening tumor was designated as the target tumor. Dose: 0.25 mL CDDP/epi gel/cm3 tumor volume. Treatments: ,6 weekly intratumoral injections in an 8-week period. Primary outcomes: target tumor response and symptom relief. Results. During the blinded phase, 34% (21 of 62) of patients achieved an objective response (CR or PR) in the target tumor treated with CDDP/epi gel vs 0% (0 of 24) treated with placebo gel (p < .001). Responses occurred within a median of four treatments (range, 2,6) and were durable (median, 95 days; range, 34,168+ days). More patients treated with CDDP/epi gel achieved palliative benefit than did those treated with placebo gel (37% vs 12%, p = .036). Most frequent side effects were local pain and local cutaneous reactions, which resolved over 3,12 weeks. Renal and hematologic toxicities were rare. Conclusions. This phase III trial showed that CDDP/epi gel significantly reduces tumor burden, palliates tumor-related symptoms, and is an effective local treatment for recurrent tumors. © 2003 Wiley Periodicals, Inc. Head Neck 25: 717,731, 2003 [source]


    Effectiveness of hepatitis C treatment with pegylated interferon and ribavirin in urban minority patients,

    HEPATOLOGY, Issue 4 2010
    Paul Feuerstadt
    Randomized controlled trials of hepatitis C virus (HCV) therapy with pegylated interferon and ribavirin have demonstrated sustained viral response rates (SVRs) of 54%-63% (efficacy). Treatment results in clinical practice (effectiveness) may not be equivalent. The goal of this study was to assess the effectiveness of HCV treatment with pegylated interferon and ribavirin in a treatment-naïve, human immunodeficiency virus (HIV)-negative, United States urban population with many ethnic minority patients. We evaluated 2,370 outpatients for HCV therapy from 2001 to 2006 in the Faculty Practice of the Albert Einstein College of Medicine or the attending-supervised Montefiore Medical Center Liver Clinic. Care was supervised by one experienced physician under conditions of everyday clinical practice, and appropriate ancillary resources were made available to all patients. Two hundred fifty-five patients were treated with a mean age of 50 years (60% male, 40% female; 58% Hispanic, 20% African American, 9% Caucasian, 13% other; 68% genotype 1, the remainder genotypes 2 or 3). Patients had at least one liver biopsy. Intention-to-treat analysis (ITT) showed SVR in 14% of genotype 1 patients and 37% in genotype 2/3 patients (P < 0.001). SVR was significantly higher in faculty practice (27%) than in clinic patients (15%) by intention-to-treat (P = 0.01) but not per-protocol analysis (46% faculty practice, 34% clinic). 3.3% of 1,656 treatment-naïve, HIV antibody,negative individuals ultimately achieved SVR. Current hepatitis C therapies may sometimes be unavailable to, inappropriate for, and ineffective in United States urban patients. Treatment with pegylated interferon and ribavirin was less effective in this population than is implied by multinational phase III controlled trials. New strategies are needed to care for such patients. (HEPATOLOGY 2010.) [source]


    Effect of extended MMX mesalamine therapy for acute, mild-to-moderate Ulcerative Colitis

    INFLAMMATORY BOWEL DISEASES, Issue 1 2009
    Michael A. Kamm MD
    Abstract Background: Many patients with ulcerative colitis (UC) respond to mesalamine therapy within 8 weeks. Those not achieving remission after 8 weeks are often treated with steroids or other immunosuppressive therapies. This study aimed to determine the effect of 8 weeks' high-dose MMX mesalamine extension therapy in patients with active, mild-to-moderate UC who had previously failed to achieve complete remission in 2 phase III, double-blind, placebo-controlled studies of MMX mesalamine (SPD476-301 and -302). Methods: Patients with active, mild-to-moderate UC who did not achieve clinical and endoscopic remission after ,8 weeks' treatment with MMX mesalamine (2.4 or 4.8 g/day), ASACOL® (mesalamine) delayed-release tablets 2.4 g/day, or placebo in the phase III studies received MMX mesalamine 4.8 g/day for 8 weeks. The aim was to assess remission at week 8, defined as a total modified UC Disease Activity Index score of ,1, calculated as: scores of 0 for rectal bleeding and stool frequency, a combined Physician's Global Assessment score and sigmoidoscopy score of ,1, no mucosal friability, and a ,1 point reduction from baseline in sigmoidoscopy score. Results: Overall, 304 patients who entered this acute extension study were evaluated; 59.5% achieved remission at week 8. Remission rates were similar irrespective of prior treatment in the initial acute phase III studies. Conclusions: Most patients with mild-to-moderate UC who fail to achieve remission with up to 8 weeks' initial mesalamine therapy can achieve clinical and endoscopic remission following a further 8 weeks' treatment with high-dose MMX mesalamine therapy, thereby avoiding step-up therapy. (Inflamm Bowel Dis 2008) [source]


    Antiadhesion molecule therapy in inflammatory bowel disease

    INFLAMMATORY BOWEL DISEASES, Issue 4 2002
    Dr. Gert Van Assche
    Abstract Adhesion molecules regulate the influx of leukocytes in normal and inflamed gut. Some of these molecules such as MadCAM-1 are specific for the gastrointestinal endothelium, but in inflammatory bowel diseases most of the adhesion factors are up-regulated. Adhesion molecules also are involved in local lymphocyte stimulation and antigen presentation within the intestinal mucosa. Recently, therapeutic compounds directed against trafficking of lymphocytes toward the gut mucosa have been designed, and are being developed as a novel class of drugs in the treatment of Crohn's disease (CD) and ulcerative colitis. This review deals with the immunological aspects of leukocyte trafficking focused on gut homing of T cells. Secondly, the changes in adhesion molecules and T-cell trafficking during intestinal inflammation are discussed. Finally, we review the clinical data that have been gathered in trials of biological therapies directed against adhesion molecules. Both antiintercellular adhesion molecule-1 (ICAM-1) and anti-,4 integrin strategies are being developed. Trials with the anti-ICAM-1 antisense oligonucleotide, ISIS-2302, in steroid-refractory CD have provided conflicting efficacy data. The anti-,4 integrin antibodies natalizumab (Antegren) and LDP-02 are in phase III and phase II trials, respectively. In the near future, these novel biological agents may prove valuable therapeutic tools in the management of refractory IBD. [source]


    Restoration of body mass in King Penguins after egg abandonment at a critical energy depletion stage: early vs late breeders

    JOURNAL OF AVIAN BIOLOGY, Issue 4 2001
    Jean-Patrice Robin
    In fasting-incubating seabirds, it has been proposed that egg abandonment and refeeding should be induced when a low body mass (BM) threshold is attained, thus ensuring adult survival at the expense of immediate breeding. In the context of life-history trade-offs in long-lived birds, we have tested this hypothesis by comparing short-term survival and restoration of BM in King Penguins Aptenodytes patagonicus that abandoned their egg to those that were relieved normally by their mate at the end of the first incubation shift. Since King Penguins have an extended laying period, the possible influence of seasonal factors was also examined by comparing early and late breeders. Forty incubating males were experimentally forced to fast until egg abandonment by preventing relief by the female. At egg abandonment of both early and late breeding males, BM was below the BM threshold, fasting duration was eight days (about 30%) longer than for relieved birds, and plasma uric acid level was elevated (signature of increased body protein catabolism, phase III of fasting). All abandoning birds survived and came back from sea at a BM similar to that of relieved penguins. The duration of the foraging trip of abandoning early breeders was the same as that of relieved birds, and some abandoning birds engaged in a new breeding attempt. Abandoning late breeders, however, made foraging trips twice as long as those of relieved males. This difference can be explained by time constraints rather than nutritional constraints, abandoning early breeders having enough time left in the breeding season to engage in a new breeding attempt in contrast to abandoning late breeders. These observations lend support to the suggestion that not only BM but also an internal clock intervene in the decision to engage in breeding or not. By preventing a lethal energy depletion ashore and by acting at a fasting stage where the capacity to restore BM at sea is unaffected, abandonment at a low body condition threshold plays a major role in the trade-off between adult penguin survival and reproduction. [source]


    Monthly Oral Ibandronate Therapy in Postmenopausal Osteoporosis: 1-Year Results From the MOBILE Study

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2005
    Paul D Miller MD
    Abstract Once-monthly (50/50, 100, and 150 mg) and daily (2.5 mg; 3-year vertebral fracture risk reduction: 52%) oral ibandronate regimens were compared in 1609 women with postmenopausal osteoporosis. At least equivalent efficacy and similar safety and tolerability were shown after 1 year. Introduction: Suboptimal adherence to daily and weekly oral bisphosphonates can potentially compromise therapeutic outcomes in postmenopausal osteoporosis. Although yet to be prospectively shown in osteoporosis, evidence from randomized clinical trials in several other chronic conditions shows that reducing dosing frequency enhances therapeutic adherence. Ibandronate is a new and potent bisphosphonate with antifracture efficacy proven for daily administration and also intermittent administration with a dose-free interval of >2 months. This report presents comparative data on the efficacy and safety of monthly and daily oral ibandronate regimens. Materials and Methods: MOBILE is a 2-year, randomized, double-blind, phase III, noninferiority trial. A total of 1609 women with postmenopausal osteoporosis were assigned to one of four oral ibandronate regimens: 2.5 mg daily, 50 mg/50 mg monthly (single doses, consecutive days), 100 mg monthly, or 150 mg monthly. Results: After 1 year, lumbar spine BMD increased by 3.9%, 4.3%, 4.1%, and 4.9% in the 2.5, 50 /50, 100, and 150 mg arms, respectively. All monthly regimens were proven noninferior, and the 150 mg regimen superior, to the daily regimen. All monthly regimens produced similar hip BMD gains, which were larger than those with the daily regimen. All regimens similarly decreased serum levels of C-telopeptide, a biochemical marker of bone resorption. Compared with the daily regimen, a significantly larger proportion of women receiving the 100 and 150 mg monthly regimens achieved predefined threshold levels for percent change from baseline in lumbar spine (6%) or total hip BMD (3%). All regimens were similarly well tolerated. Conclusions: Monthly ibandronate is at least as effective and well tolerated as the currently approved daily ibandronate regimen in postmenopausal osteoporosis. [source]


    Advances in mechanisms of postsurgical gastroparesis syndrome and its diagnosis and treatment

    JOURNAL OF DIGESTIVE DISEASES, Issue 2 2006
    Ke DONG
    Postsurgical gastroparesis syndrome (PGS) is a complex disorder characterized by post-prandial nausea and vomiting, and gastric atony in the absence of mechanical gastric outlet obstruction, and is often caused by operation at the upper abdomen, especially by gastric or pancreatic resection, and sometimes also by operation at the lower abdomen, such as gynecological or obstetrical procedures. PGS occurs easily with oral intake of food or change in the form of food after operation. These symptoms can be disabling and often fail to be alleviated by drug therapy, and gastric reoperations usually prove unsuccessful. The cause of PGS has not been identified, nor has its mechanism quite been clarified. PGS after gastrectomy has been reported in many previous studies, with an incidence of approximately 0.4,5.0%. PGS is also a frequent complication of pylorus-preserving pancreatoduodenectomy (PPPD), and the complication occurs in the early postoperative period in 20,50% of patients. PGS caused by pancreatic cancer cryoablation (PCC) has been reported about in 50,70% of patients. Therefore, PGS has a complex etiology and might be caused by multiple factors and mechanisms. The frequency of this complication varies directly with the type and number of gastric operations performed. The loss of gastric parasympathetic control resulting from vagotomy contributes to PGS via several mechanisms. It has been reported that the interstitial cells of Cajal (ICC) may play a role in the pathogenesis of PGS. Recent studies in animal models of diabetes suggest specific molecular changes in the enteric nervous system may result in delayed gastric emptying. The absence of the duodenum, and hence gastric phase III, may be a cause of gastric stasis. It was thought that PGS after PPPD might be attributable, at least in part, to delayed recovery of gastric phase III, due to lowered concentrations of plasma motilin after resection of the duodenum. The damage to ICC might play a role in the pathogenesis of PGS after PCC, for which multiple factors are possibly responsible, including ischemic and neural injury to the antropyloric muscle and the duodenum after freezing of the pancreatoduodenal regions or reduction of circulating levels of motilin. As the treatment of gastroparesis is far from ideal, non-conventional approaches and non-standard medications might be of use. Multiple treatments are better than single treatment. This article reviews almost all the papers related to PGS from various journals published in English and Chinese in recent years in order to facilitate a better understanding of PGS. [source]


    A quality assurance audit: Phase III trial of maximal androgen deprivation in prostate cancer (TROG 96.01)

    JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 1 2000
    A Steigler
    SUMMARY In 1997 the Trans-Tasman Radiation Oncology Group (TROG) performed a quality assurance (QA) audit of its phase III randomized clinical trial investigating the effectiveness of different durations of maximal androgen deprivation prior to and during definitive radiation therapy for locally advanced carcinoma of the prostate (TROG 96.01). The audit reviewed a total of 60 cases from 15 centres across Australia and New Zealand. In addition to verification of technical adherence to the protocol, the audit also incorporated a survey of centre planning techniques and a QA time/cost analysis. The present report builds on TROG's first technical audit conducted in 1996 for the phase III accelerated head and neck trial (TROG 91.01) and highlights the significant progress TROG has made in the interim period. The audit provides a strong validation of the results of the 96.01 trial, as well as valuable budgeting and treatment planning information for future trials. Overall improvements were detected in data quality and quantity, and in protocol compliance, with a reduction in the rate of unacceptable protocol violations from 10 to 4%. Audit design, staff education and increased data management resources were identified as the main contributing factors to these improvements. In addition, a budget estimate of $100 per patient has been proposed for conducting similar technical audits. The next major QA project to be undertaken by TROG during the period 1998,1999 is an intercentre dosimetry study. Trial funding and staff education have been targeted as the key major issues essential to the continued success and expansion of TROG's QA programme. [source]