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  • 1
    ISSN: 1432-1084
    Keywords: Key words: MR imaging – CT – Rectum – Neoplasms – Comparative studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The aim of this study was to compare three imaging strategies for the diagnosis of local recurrence of rectal cancer: (a) MR imaging; (b) MR imaging after administration of enteral superparamagnetic particles (Ferristene); and (c) contrast-enhanced CT. Seventeen patients with previous surgery for rectal cancer were examined, 12 patients with local tumour recurrence in the pelvis and 5 patients with postoperative changes. Pelvic multi-coil MR imaging before and after oral administration of superparamagnetic contrast medium [Abdoscan (Ferristene USAN), Nycomed-Amersham, Lidingö, Sweden] as well as abdominal and pelvic CT was performed in all patients. The examinations were independently evaluated by three different radiologists. The general effect of the oral MR contrast medium, the delineation of normal and pathological structures as well as confidence in the diagnosis were registered on a visual analog scale (VAS). The diagnosis according to MR before and after oral contrast medium, and CT, was compared, in 16 patients, with the final diagnosis which was verified by biopsy (n = 3), surgery (n = 6), clinical follow-up (n = 4) and by follow-up with MR or CT (n = 3). No significant improvement in MR image quality was found after enteral contrast medium. The post-contrast MR diagnosis was not changed in any of the patients. The diagnosis on MR correlated with the final diagnosis in 12 of 16 patients (sensitivity 91 %, accuracy 62 %) and the diagnosis on CT in 11 of 16 patients (sensitivity 82 %, accuracy 56 %). The radiologists' “confidence” in the diagnosis and the degree of accordance with the final diagnosis did not score higher on MR after than before oral contrast administration; however, the accordance with the final diagnosis scored better on MR than on CT. No advantages of orally administered superparamagnetic contrast medium were observed in the examined patient group. Magnetic resonance is preferable to CT in diagnosing local tumour recurrence.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: Key words Topotecan ; Cytotoxicity assay ; Human tumor cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Combination therapies are important in the treatment of many tumor types. This study was undertaken to find candidates for combination therapy with the novel topoisomerase I inhibitor topotecan. Methods: The cytotoxic effect of topotecan alone and in combination with five standard cytotoxic drugs was studied in 27 primary cultures of human tumor cells from patients with various diagnoses using the fluorometric microculture cytotoxicity assay (FMCA). The combinations were analysed according to the multiplicative concept of drug interaction. Results: The additive model was shown to be a better descriptor than the effect of the most effective agent (Dmax) for all drug combinations tested. Topotecan in combination with cisplatin (CisP) was the drug combination showing synergy in the highest percentage of samples (54%), followed by topotecan in combination with doxorubicin (Dox; 39%), etoposide (P16; 23%), paclitaxel in the formulation Taxol (22%) and cytarabine (AraC; 12%). The high percentage of synergistic interactions was especially pronounced in solid tumors. In 28% of the samples tested, drug sensitivity testing of only single drugs failed to predict response to the drugs in combination. Conclusion: Cisplatin and doxorubicin showed promising effects in combination with topotecan, and clinical trials with these combinations seem warranted. The results also indicate the value of testing drug combinations in in vitro drug sensitivity testing.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Livestock Production Science 12 (1985), S. 279-285 
    ISSN: 0301-6226
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Livestock Production Science 11 (1984), S. 179-184 
    ISSN: 0301-6226
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Sound and Vibration 26 (1973), S. 571-575 
    ISSN: 0022-460X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Tetrahedron Letters 8 (1967), S. 3675-3678 
    ISSN: 0040-4039
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Incidence studies offer a better opportunity to study risk factors for asthma than do prevalence studies. However, regular prospective follow-ups of large cohorts are difficult to perform, and that is why direct measurement of the incidence rate of asthma is almost impossible. Thus, cross-sectional follow-up studies of defined cohorts can be used to provide data on incidence. In 1986, a postal questionnaire survey on respiratory symptoms and diseases was performed in the northernmost province of Sweden. The population sample comprised all subjects born in 1919—20, 1934—5, and 1949—50 in eight representative areas of the province, which comprises 25% of the total area of Sweden. Completed answers were given by 5698 subjects (86%) of the 6610 subjects invited to the study. In 1992, the cohort was invited to a follow-up survey during the same season as in 1986, and 6215 subjects were traced. Of the 5393 subjects who answered the questionnaire, 4932 had participated in the 1986 survey, or 87% of those who participated in 1986. For the period 1986—92, the cumulative incidences of asthma were 4.9 and 5.0%, respectively, as assessed by the questions, “Have you ever had asthma?” and “Have you been diagnosed as having asthma by a physician?” Thus, the results indicate a mean annual cumulative incidence of asthma of 0.8%. After correction of the results for subjects who were diagnosed as having asthma in the clinical part later in the 1986 study, the mean annual cumulative incidence of asthma was found to be 0.5%. Risk factors were family history of asthma (OR 3.46) and current and former smoking, while female sex was a strong trend.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 16 (1999), S. 1260-1265 
    ISSN: 1573-904X
    Keywords: model selection ; mixed effects modeling ; jackknife ; case deletion ; NONMEM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Data from single individuals, or a small group of subjects may influence non-linear mixed effects model selection. Diagnostics routinely applied in model building may identify such individuals, but these methods are not specifically designed for that purpose and are, therefore, not optimal. We describe two likelihood-based diagnostics for identifying individuals that can influence the choice between two competing models. Methods. One method is based on a jackknife of the raw data on the individual level and refitting the model to each new data set. The second method is a calculation which utilises the contribution each individual make to the objective function values under each of the two models. The two methods were applied to model selection during analysis of a real data set. Results. The agreement between the methods was high. Individuals for whom there was a discrepancy between the methods tended to be those for which neither of the contending models described the data appropriately. Both methods identified individuals that influenced the model selection. Conclusions. Two objective, specific and quantitative methods for identifying influential individuals in nonlinear mixed effects model selection have been presented. One of the methods doesn't require additional model fitting and is therefore particularly attractive.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 14 (1997), S. 984-991 
    ISSN: 1573-904X
    Keywords: compliance ; dosing history ; NONMEM ; population pharmacokinetic analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. In population pharmacokinetic studies, the dosing history is sometimes recorded in more than one way. The purpose of this study was to develop and evaluate a procedure for discriminating between rival dosing histories, i.e., for each individual in a data set, identify the dosing history that is the most plausible. Methods. The procedure consists of four steps. In the first step we identify individuals whose dosing histories produce predictions that are consistent. In the second step these individuals are used to build a population pharmacokinetic model which is used, in step three, to select the dosing history for the individuals not identified in step one. In step four the population model is refined using the best available dosing histories for all individuals. The proposed procedure was evaluated using both simulations and a real data set, in which two dosing histories, based on patient diaries and electronic monitoring devices (MEMS) were available. Results. In the real data set, estimated variabilities were almost always lower when the selected dosing histories were used compared to when no selection procedure was used. The diary dosing histories were selected more often than the MEMS dosing histories. In the simulations, the parameter estimates obtained using the selection procedure were closer to the true parameter values compared to when only one of the dosing histories was used. Conclusions. The proposed procedure appears to be robust and should be beneficial in at least two respects: improved parameter estimation of population pharmacokinetic and PK/PD models and objective information by which dosage recording methodologies can be compared and patient dose recording behavior can be assessed.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 15 (1998), S. 1463-1468 
    ISSN: 1573-904X
    Keywords: covariate model building ; NONMEM ; population pharmacokinetic analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. One important task in population pharmacokinetic/pharmacodynamic model building is to identify the relationships between the parameters and demographic factors (covariates). The purpose of this study is to present an automated procedure that accomplishes this. The benefits of the proposed procedure over other commonly used methods are (i) the covariate model is built for all parameters simultaneously, (ii) the covariate model is built within the population modeling program (NONMEM) giving familiar meaning to the significance levels used, (iii) it can appropriately handle covariates that varies over time and (iv) it is not dependent on the quality of the posterior Bayes estimates of the individual parameter values. For situations in which the computer run-times are a limiting factor, a linearization of the non-linear mixed effects model is proposed and evaluated. Methods. The covariate model is built in a stepwise fashion in which both linear and non-linear relationships between the parameters and covariates are considered. The linearization is basically a linear mixed effects model in which the population predictions and their derivatives with respect to the parameters are fixed from a model without covariates. The stepwise procedure as well as the linearization was evaluated using simulations in which the covariates were taken from a real data set. Results. The covariate models identified agreed well with what could be expected based on the covariates that were actually supported in each of the simulated data sets. The predictive performance of the linearized model was close to that of the non-linearized model. Conclusions. The proposed procedure identifies covariate models that are close to the model supported by the data set as well as being useful in the prediction of new data. The linearized model performs nearly as well as the non-linearized model.
    Type of Medium: Electronic Resource
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