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At least 595 records · Page 33Linked to original sources

Study on the bioequivalence of an oral nifedipine formulation and a sustained release reference preparation after single dose and repeated doses.

Pharmacokinetic parameters of an oral formulation of nifedipine (CAS 21829-25-4, Corinfar, test preparation T a dragee with 10 mg nifedipine) were compared with a reference preparation (R, a sustained release tablet with 20 mg nifedipine) in 16 healthy volunteers in a open two-way crossover study under the influence of ingestion of food. A GC/MS method was used to analyse the serum samples. The estimation of bioequivalence was based on a nonparametric statistical procedure of analysis of variance. Both, the test preparation T and the reference preparation R are bioequivalent at steady state. The main pharmacokinetic parameters (mean +/- standard deviation) used for the bioequivalence decision at steady state were AUC0- tau ss (T: 351.4 +/- 161.0 ng.ml-1.h; R: 345.5 +/- 146.8 ng.ml-1.h), Cmaxss (T: 67.3 +/- 29.5 ng.ml-1; 66.9 +/- 33.0 ng.ml-1) and HVDss (T: 3.8 +/- 1.3 h; R: 4.2 +/- 1.8 h). The bioequivalence of rate and extent of absorption was proved for both preparations at steady state by assessing mean serum level curves as well as by statistics (90% confidence intervals) using the main pharmacokinetic parameters AUC0 - tau ss (range: 0.84-1.02 point estimator: 0.92), Cmaxss (0.95-1.33; 1.15) HVDss (0.72-0.98; 0.82). The large interindividual variability of pharmacokinetics is typical of the drug and does not depend on the formulation used. No case of severe disturbance of circulatory function or other adverse events with the duty to treat occurred during the study. No volunteer dropped out.

Administration, Oral↗

Reconstruction of the immune system after unrelated or partially matched T-cell-depleted bone marrow transplantation in children: immunophenotypic analysis and factors affecting the speed of recovery.

We prospectively studied immune reconstitution in 102 children who underwent T-lymphocyte depleted bone marrow transplants using either closely matched unrelated donors or partially matched familial donors by assaying total lymphocyte counts (TLC), T-cell subsets, B cells, and natural killer cells. TLC, CD3+, and CD4+ T-cell counts remained depressed until 2 to 3 years posttransplant, whereas CD8+ T-cell counts normalized by 18 months, resulting in an inverted CD4:CD8 ratio until 12 months posttransplant. Although the percentage of NK cells was elevated early posttransplant, their absolute numbers remained normal. CD20+ B cells were depressed until 12 to 18 months posttransplant. Factors affecting immunophenotypic recovery were analyzed by nonparametric statistics. Younger patients tended to have higher TLC posttransplant. Higher marrow cell doses were not associated with hastened immunophenotypic recovery. Graft-versus-host disease (GVHD) and/or its treatment significantly delayed the immune reconstitution of CD3+, CD4+, and CD20+ cells. The presence of cytomegalovirus was associated with increased CD8+ counts and a decrease in the percentages of CD4+ and CD20+ cells.

Adolescent↗

[The advantages of associating ischemia/reperfusion injury inhibitors with intravenous thrombolysis when treating focal brain ischemia: a description of experiments using rats].

Restoration of blood flow is necessary when treating brain ischemia. However, except in very early cases, this is insufficient to prevent the cascade of mediators of cell damage unleashed by ischemia which, on the other hand, is boosted by the deleterious effects of reperfusion. We therefore consider adequate treatment for brain ischemia ought to associate, early on, reperfusion with pharmacological inhibition of those intermediaries in damage caused by ischemia/reperfusion (cytoprotection), basically an excess of cytosolic calcium and of free radicals. In this way, spreading of the infarct may be avoided more effectively than just with reperfusion alone. Our aim was to demonstrate this hypothesis using an experimental model. In order to do so, we shall embolize the right carotid artery territory of 50 Long Evans rats with autologous blood thrombi and check the location of the embolus using arteriography. Forty rats will receive thrombolytic treatment intravenously (rTPA at a dose of 20 mg/kg) two hours after embolization, while 10 control rats will receive similar treatment with saline serum. The thrombolysis treated animal group will be divided into four subgroups (A, B, C, D, ni = 10). Group A will be considered as the thrombolysis control group; group B will additionally receive calcium antagonists (dihydropyridines); group C will undergo antioxidant treatment (21-aminosteroids) and group D both calcium antagonists and antioxidants in association with thrombolysis. The size of infarct produced in each group, estimated following Cavalieri's principle, will be compared using nonparametric statistical tests (Mann-Whitney test and Willcoxon test). We present the preliminary results so obtained in a group of 14 control rats studied with the aim of assessing the usefulness of the proposed model.

Animals↗

Experiences in the first year. Community hospital pediatric trauma center.

Demographic and outcome variables of children seen in a community hospital Level II pediatric trauma center are described and patterns of injury classified according to different mechanisms. Records were reviewed retrospectively of 184 patients seen over a one year period, 63% were male and the peak age group was 13-15 years (31%). Descriptive and nonparametric statistics were used to analyze the data. Mechanisms of injury included pedestrian vs auto (27%), falls (23%), motor vehicle occupants (18%), bicycle vs auto (17%), sports injuries (3%), motorcycle crashes (2%), gunshot wounds (2%), and stabbings (2%). Penetrating injuries had higher average trauma scores but blunt injuries were associated with higher mortality. Demographics and mechanisms of injury were similar to national studies. Emphasis on the use of pediatric trauma scores by emergency medical personnel is suggested to decrease the over-triage rate. The frequency of bicycle injuries and lack of helmet use prompted a major helmet promotion campaign.

Accidental Falls↗

Detection of structural damage from glaucoma with confocal laser image analysis.

PURPOSE: To determine which structural optic nerve head parameters measured with confocal scanning laser image analysis that best discriminate between normal persons and those with glaucoma. METHODS: One randomly selected eye of 53 patients with early open-angle glaucoma (average visual field mean deviation = -4.8 dB) and of 43 age-, race-, and refractive error-matched normal subjects were studied. The performance of nine structural measures was evaluated with linear multivariate analysis and a neural network: cup area, cup to disc area ratio, rim area, height variation contour, cup volume, rim volume, cup shape measure, mean retinal nerve fiber layer thickness, and retinal nerve fiber layer cross-section area. A discriminant function was derived with two thirds of the sample and its discriminant power tested on the remaining one third. This was repeated twice so that the entire sample was used for training and testing. A neural network was trained and tested in the same way. Stereoscopic color optic nerve photographs of the same eyes were evaluated qualitatively by three experienced, masked observers. Receiver operating characteristic (ROC) curves of discriminant function, neural network results, and qualitative evaluation were plotted. Comparisons of the areas under the ROC curves were performed with nonparametric statistics. RESULTS: There were statistically significant differences between the normal and glaucoma groups for all measures (P < or = 0.007) except for height variation contour, mean retinal nerve fiber layer thickness, and retinal nerve fiber layer cross-section area. Cup shape measure provided the single best measure to distinguish between normal subjects and those with early glaucoma and had a diagnostic precision of 84%. Neural network diagnostic precision, when all measures were used, was 92% and decreased to 82% when cup shape measure was omitted. The area under the ROC curve when all measures were combined was 0.94; it was significantly lower (P = 0.04) when cup shape measure was omitted (area = 0.84). The area under the ROC curve for qualitative optic disc evaluation by experienced observers was 0.93. There was no statistically significant difference between qualitative evaluation and neural network performance (P = 0.80). CONCLUSIONS: Cup shape measure, the statistical third moment of the distribution of depth values of the optic nerve head obtained with confocal laser image analysis, can be used to discriminate between normal persons and those with early glaucomatous damage with high diagnostic precision.

Female↗

[Study of critical values of plasma concentration of cholesterol in hospitalized patients by an enzymatic method].

The concentration of plasma cholesterol was measured in 794 women and 832 men by a method of enzyme analysis. The populations studied were composed of patients in hospital. The critical values were drawn up using parametric and nonparametric statistical methods. The serum cholesterol varied in these populations between 3.0 and 8.5 mmol/l and neither age nor sex modified seriously these values.

Adult↗

(32)P-postlabeling detection of DNA adducts in peripheral white blood cells of greenhouse floriculturists from western Liguria, Italy.

Pesticides are widely used in agriculture to enhance crop yields and to control disease vectors. Floriculturists work frequently in greenhouses and may be exposed to high levels of pesticides, which may result in adverse health effects. To evaluate the relationship between exposure to pesticides and DNA adduct formation in peripheral WBCs of Italian floriculturists, the nuclease P1 modification of a (32)P-postlabeling assay was used to analyze WBC DNA from floriculturists (n = 26) and matched controls (n = 22). DNA adduct-positive samples were more frequent in floriculturists (11/26; 42%) than in matched controls (2/22; 9%) (P < 0.01). Slightly higher frequencies of DNA adduct-positive samples were observed in floriculturists > or = 44 years of age (53%) and in female floriculturists (57%). Floricultural practice was found to be associated with a significantly higher DNA adduct-positive rate in WBCs (rate ratio, 5.12; 95% confidence interval, 1.1-23.7) after allowing for the effects of age and gender. These two latter covariates were not significantly associated with DNA adduct-positive rates. The quantitative levels of DNA adducts were significantly higher in floriculturists than in matched controls according to the Mann-Whitney nonparametric statistic (P = 0.0052). The median adduct level for positive samples among floriculturists was 1.5/10(8) bases. A specific, well-visible spot, named alpha adduct, was detected in 7 out of the 11 DNA adduct-positive samples from floriculturists but in none of the (22 + 20) referent samples (P = 0.0004). The presence of pesticide-related DNA adducts was confirmed clearly using the butanol extraction procedure. Six of 8 floriculturists and 0 of 10 referents were found positive with this method. The median adduct level for positive samples was 6.0/10(8) bases. Two strong spots close to the origin could be identified in all six positive floriculturists, using the butanol extraction procedure. No association between DNA adducts and use of specific pesticides was observed.

Adult↗

Comparative bioavailability of two atenolol tablet formulations in healthy male volunteers after a single dose administration.

The bioavailability of 2 atenolol tablet formulations (Angipress from Laboratórios Biosintética, and Atenol from Wellcome ICI Laboratory, Brazil) were compared in 18 healthy male volunteers who received a single 50 mg dose of each atenolol formulation. The study was conducted following an open randomized 2-period crossover design with a 14-day washout interval between doses. Plasma samples were obtained over a 24-hour interval and atenolol concentrations were determined by HPLC with fluorimetric detection. From the plasma atenolol concentration vs time curves the following pharmacokinetic parameters were obtained: AUC(zero-24) (area under the concentration vs time curves from 0-24 h), ke (terminal elimination constant), t1/2 (terminal first order elimination half-life), AUC (area under the concentration vs time curves extrapolated to infinity), Cmax (maximum achieved concentration), Tmax (time to achieve Cmax) and Cmax/AUC. All these variables were analyzed using both parametric and nonparametric statistics. Geometric mean Angipress/Atenol individual percent ratios were 99.6% for AUC(zero-24), 99.7% for AUC, 98.0% for Cmax, 102.8% for t1/2, 97.2% for ke and 97.8% for Cmax/AUC, with all their 90% confidence intervals within the bioequivalence range 80-125%, thus showing similar patterns of absorption and disposition. Arithmetic mean for individual Tmax differences was 0.8 h, and the 90% confidence interval did not include the zero value. Based on these results and in accordance with the European Union and the US Food and Drug Administration bioequivalence requirements we conclude that both atenolol formulations are bioequivalent for both the extent and the rate of absorption.

Administration, Oral↗

Endothelin-1 as a putative modulator of gene expression and cellular physiology in cultured human corporal smooth muscle cells.

PURPOSE: Increases in cytosolic calcium levels trigger smooth muscle contraction while nuclear calcium increases are thought to regulate gene expression. Endothelin-1 (ET-1) affects both. The goal of these studies was to further investigate the importance of ET-1 to corporal physiology by examining its actions on proliferation and immediate early gene (IEG) expression in cultured human corporal smooth muscle cells. MATERIALS & METHODS: Early passage (1-3) smooth muscle cells were grown in culture and exposed to either phenylephrine (PE) or ET-1 in the absence and presence of serum, the ET(A) or ET(B) selective antagonist BQ123 or IRL1038, or the L-type Ca2+ channel blocker, verapamil. Cell proliferation was assessed with a hemocytometer. The effects of ET-1 on c-myc and c-fos were evaluated using Northern blot analysis. Parametric or nonparametric statistics were used as appropriate. RESULTS: Addition of ET-1 (100 nM) to serum-starved cultured corporal smooth muscle cells was associated with a nearly 2-fold increase in cell number, as well as 2 to 6-fold increases in c-myc and c-fos levels. Cellular proliferation was inhibited by ET(A)- or ET(B)-receptor subtype blockade with BQ123 (1 microM) or IRL1038 (1 microM), respectively, or blockade of Ca2+ channels with verapamil (10 microM). PE (3 microM) had no detectable effect on smooth muscle proliferation. CONCLUSIONS: Cell proliferation was mediated by activation of the ET(A) and ET(B) receptor subtypes, dependent on transmembrane Ca2+ flux, and correlated with significant increases in c-myc and c-fos mRNA levels. These studies extend previous observations to indicate the potential pleotropic actions of this peptide in the regulation of human corporal smooth muscle physiology in vivo.

Adult↗

Cellular adhesion molecules changes in myocardium during first year post heart transplant.

The increased presence of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) in the myocardium after orthotropic heart transplantation (OHT) has been implicated in early and late organ rejection. The aim of this study was to investigate the changes in ICAM-1 and VCAM-1 during the first years post-OHT. Accordingly, we studied multiple endomyocardial biopsy specimens collected from 11 randomly selected patients (all males, mean age 46 +/- 11 years). Qualification criteria for OHT included: ischemic cardiomyopathy in 6 pts (55%) and idiopathic dilated cardiomyopathy in 5 pts (45%). All patients were receiving triple immunosuppressive regimen. The therapy consisted of cyclosporine, azathioprine, and prednisolone. Multiple endomyocardial biopsy specimens were collected at 7, 30, 90 and 360 days post OHT from all patients (pts), and examined routinely for histologic signs of organ rejection. To assess levels of adhesion molecules we used monoclonal antibodies (murine anti-human ICAM-1 and VCAM-1) on frozen sections. Immunoreactivity (IR) was detected using a commercially available kit. Intensity of IR was assessed based on a semiquantitative scoring system. In this study, IR scores > or = 2 + were considered positive for ICAM-1, and scores > or = 1 + were considered positive for VCAM-1. IR scores in specimens obtained from consecutive biopsies were compared with the initial biopsy collected at the day 7. The results were analyzed using nonparametric statistics. The routine evaluation revealed histological signs of organ rejection (> or = 2) in 2 pts at 7 days, in 5 pts at 30 days, in 3 pts at 90 days, and in 1 patient at 360 days. On the other hand, ICAM-1 and VCAM-1 expression were absent in the majority of patients at 7, 30 and 90 days, but their presence was significantly increased at 360 days (p < 0.05). Absence of the early expression of ICAM-1 and VCAM-1 may be related to the protective effect of triple immunosuppressive therapy in these patients. The expression of ICAM-1 and VCAM-1 strongly emerging at 1 year post OHT may reflect chronic rejection in myocardium. In conclusion, the immunohistological monitoring of the adhesion molecules in biopsy specimens during routine biopsy schedule may be helpful for the discovery of chronic rejection.

Adult↗

[Modern methods of medical rehabilitation in traumatic detachment of retina].

The authors analyze the efficacy of treating patients with vitreoretinal diseases using a pathogenetically-based system of comprehensive medical rehabilitation and the results of ophthalmological examination recorded and processed in a special computer case history. Prognostic analysis making use of nonparametrical statistics method distinguished highly informative signs determining the results of medical rehabilitation in traumatic detachment of the retina. Basic methods of surgical rehabilitation are supplemented with preventive YAG laser surgery. Modern scleroplastic materials are offered. The authors emphasize the significance of two staged adequate postoperative rehabilitation during the immediate postoperative period with special emphasis on the agents regulating redox processes; later YAG lasers and other stimulators can be used. Other perspective trends of research are study of electroenesis and pathogenesis of vitreoretinal proliferation for drug development.

Eye Injuries↗

Nonparametric analysis of statistic images from functional mapping experiments.

The analysis of functional mapping experiments in positron emission tomography involves the formation of images displaying the values of a suitable statistic, summarising the evidence in the data for a particular effect at each voxel. These statistic images must then be scrutinised to locate regions showing statistically significant effects. The methods most commonly used are parametric, assuming a particular form of probability distribution for the voxel values in the statistic image. Scientific hypotheses, formulated in terms of parameters describing these distributions, are then tested on the basis of the assumptions. Images of statistics are usually considered as lattice representations of continuous random fields. These are more amenable to statistical analysis. There are various shortcomings associated with these methods of analysis. The many assumptions and approximations involved may not be true. The low numbers of subjects and scans, in typical experiments, lead to noisy statistic images with low degrees of freedom, which are not well approximated by continuous random fields. Thus, the methods are only approximately valid at best and are most suspect in single-subject studies. In contrast to the existing methods, we present a nonparametric approach to significance testing for statistic images from activation studies. Formal assumptions are replaced by a computationally expensive approach. In a simple rest-activation study, if there is really no activation effect, the labelling of the scans as "active" or "rest" is artificial, and a statistic image formed with some other labelling is as likely as the observed one. Thus, considering all possible relabellings, a p value can be computed for any suitable statistic describing the statistic image. Consideration of the maximal statistic leads to a simple nonparametric single-threshold test. This randomisation test relies only on minimal assumptions about the design of the experiment, is (almost) exact, with Type I error (almost) exactly that specified, and hence is always valid. The absence of distributional assumptions permits the consideration of a wide range of test statistics, for instance, "pseudo" t statistic images formed with smoothed variance images. The approach presented extends easily to other paradigms, permitting nonparametric analysis of most functional mapping experiments. When the assumptions of the parametric methods are true, these new nonparametric methods, at worst, provide for their validation. When the assumptions of the parametric methods are dubious, the nonparametric methods provide the only analysis that can be guaranteed valid and exact.

Algorithms↗

[Rank transformations--the connection between nonparametric and parametric statistics].

The purpose of this paper is to present the relationship between nonparametric and parametric analysis by means of rank transformation. It is shown that in case of large sample, the resulting statistics getting from Wilcoxon rank test, Kruskal-Wallis and Friedman rank test are equivalent to the ratio of the sum of squares for treatment divided by mean square for the total variability calculated by ranks in the manner of the analysis of variance. It is also suggested that this method can be extended to factorial design experiments, and a detail procedure is given.

Multivariate Analysis↗

[Examples of pitfalls in statistical analysis--2. Parametric and nonparametric analyses].

When conducting statistical analysis, it is essential to use parametric and nonparametric analyses which properly accord with the attributions of data. What is often overlooked, however, is the need to select the most suitable method of spatistical analysis for the model of the studies. Parametric analysis certainly cannot be relied upon in all situations to yield the best resolutions, and even if we strictly distinguish between the use of parametric and that of nonparametric analyses, we still have done nothing to improve the resolutions themselves. In this article, I discuss several frequently asked questions by presenting an example in which I use parametric analysis on data that should be analyzed by nonparametric analysis.

Drug-Related Side Effects and Adverse Reactions↗

Simple bootstrap statistical inference using the SAS system.

Nonparametric bootstrap statistical inference is a robust computer intensive method for generating estimates of statistical variability for which formulae are not known or asymptotic assumptions are not met. A SAS macro that implements simple nonparametric bootstrap statistical inference is presented with an example. The program code is easily generalized to any SAS procedure which includes a BY statement, and to cases of clustered data.

Data Interpretation, Statistical↗

Introduction to biostatistics: Part 5, Statistical inference techniques for hypothesis testing with nonparametric data.

Specific statistical tests are used when the null hypothesis (H0) is to be tested using nonparametric nominal or ordinal data. With nominal data, experimental results are expressed by proportions or frequencies. Chi-square or related tests (the Fisher's exact test or the rows by columns test) are appropriate for testing H0 with nominal data. Ordinal data permit arrangement of statistical results by rank. Rank-order tests used to test H0 with ordinal data include the Mann-Whitney U, Kolmogorov-Smirnov, Wilcoxon, Kruskal-Wallis, and Friedman tests. The Kruskal-Wallis and Friedman tests permit multiple intergroup comparisons. Other rank-order tests permit only single intergroup comparisons. Specific details to guide the researcher in the proper selection of these tests are presented.

Statistics as Topic↗