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PubMed1989

Heterogeneity of growth hormone (GH) release by individual pituitary adenoma cells from acromegalic patients, as determined by the reverse hemolytic plaque assay: effects of SMS 201-995, GH-releasing hormone and thyrotropin-releasing hormone.

We used the reverse hemolytic plaque assay to study the dynamics of GH secretion by individual pituitary adenoma cells from eight acromegalic patients. There was a considerable variation between the adenomas with respect to the percentages of GH-secreting cells (25-78.5%) and also with respect to the amount of GH released per individual pituitary adenoma cell (mean plaque areas varying from 901-3559 micron 2). The GH plaque area frequency distributions from the adenoma cells were not normally distributed, but revealed a preponderance of small plaques, defined as those with areas smaller than the mean plaque area. The large plaques, that is those with areas larger than the mean plaque area, constituted 24-38% of the total cell population from different tumors and accounted for a large fraction (63-80%) of the total plaque area (the total amount of GH released by the adenoma cells). The somatostatin analog SMS 201-995 caused a shift in the GH plaque area frequency distributions toward smaller plaques, but had no effect on the overall percentages of GH plaque-forming cells in three of the five adenomas in which it was studied. This finding suggests that the adenoma cells from these patients that formed large plaques were preferentially inhibited by SMS 201-995. GHRH (studied in two adenomas) and TRH (studied in one adenoma) had no preferential effect on any subpopulation of adenoma cells. We conclude that GH secretion by individual somatotroph adenoma cells is highly variable both within and between adenomas and that SMS 201-995 has a preferential inhibitory effect on a subpopulation of adenoma cells in some adenomas.

Acromegaly↗
PubMed2004

Probabilistic uncertainty analysis of the European Union system for the evaluation of substances multimedia regional distribution model.

The European Union System for the Evaluation of Substances (EUSES) is a computerized model system to facilitate and harmonize health and environmental risk assessment of previously notified and new substances. For calculation of regional background exposure, a multimedia distribution model is used. In the present study, the uncertainty of this regional model is analyzed. Environmental parameters were collected for North Rhine Westphalia (Germany), which resembles the standard region of EUSES. Probability distribution functions of various types (uniform, triangular, normal, log normal) depending on data availability were derived for environmental input parameters, including geometric parameters. Generic log-normal distribution functions with fixed standard deviations were chosen for solubility in air, water, and n-octanol as well as for degradation half-lives. Monte Carlo simulations were carried out for 10 reference substances having different properties. Contribution of environmental parameter uncertainty to total output uncertainties is higher than that of substance parameters. Range of output uncertainty, defined as the ratio of the logarithms of the 90th and 10th percentiles of the cumulative probability distribution function, shows an increase from air and water to soil. The highest-occurring range is 1.4 orders of magnitude, which means that total uncertainty of the regional model is relatively low and, usually, is lower than the range of measured values. The median of output probability distributions lies above the point estimate. Influence of input parameters was estimated as their rank correlation coefficients to output uncertainty. Substance and environmental parameters contribute differently to output variance depending on individual substance properties and environmental compartment. Hence, the present study underlines the need to perform uncertainty analyses instead of either using a set of simple rules or just looking at certain parameters.

Environment↗
PubMed2003

Delta-aminolevulinic acid dehydratase activity in the general population of southern Minas Gerais, Brazil.

Blood samples were collected from 113 subjects (56 males and 57 females) living in the district of Alfenas, in southern Minas Gerais state, Brazil, to establish reference values for delta-aminolevulinic acid dehydratase activity (ALA-D, EC 4.2.1.24). The state of health of the population was confirmed by hematological and biochemical parameters analyzed in blood and urine samples. ALA-D determination was performed according to the Berlin & Schaller spectrophotometric method. Distribution may be regarded as according to normal distribution and reference values obtained, in micromol x min(-1) x L(-1) erythrocytes, were: mean (+/- SD) = 54.5 (+/- 9.8); 95% confidence interval = 52.7-56.4; lower reference value (mean-2 SD) = 34.9. Mean ALA-D activity was higher than any other published elsewhere and the reference values established are useful as a baseline for evaluating ALA-D activity when monitoring persons exposed to lead. Age, gender, drinking, or smoking did not significantly alter (Student t-test, p < or = 0.05) the reference values for ALA-D.

Adolescent↗
PubMedDate not supplied

Ultrastructural morphometric study of follicular center lymphocytes: I. Nuclear characteristics and the Lukes-Collins' concept.

A combined ultrastructural and morphometric image analysis study was carried out on the nuclear profiles of follicular center and mantle zone lymphocytes of six cases of reactive hyperplasia in human lymph node biopsies. For accuracy of morphological observations and sampling at low magnifications, sections were mounted on formvar-covered slot grids. Measurements of nuclear profile features of small (untransformed) lymphocytes in mantle zones served as the standard for a supposed unimodal population in each case. Analysis of nuclear profile area values indicated that during lymphocyte transformation in follicular centers nuclei had a gradual and progressive increase in size and that the sampled nuclear profiles in both the mantle zone and follicular center were unimodal. Lymphocyte nuclear shape (contour index) was a more complex, and likely biologically independent, feature than nuclear area in both the mantle zone and follicular center. Nuclear profile contour indexes of mantle zone lymphocytes were more irregular than suspected and in some cases had mean values greater than those of follicular center lymphocytes. Furthermore, the frequency distribution of nuclear contour index was not normally distributed in either the follicular center or mantle zone due to the presence of a small proportion of highly irregularly shaped nuclear profiles in both sites. The results indicated that some premises of existing concepts of follicular center cells and the process of lymphocyte transformation in follicular centers were incorrect and should not be directly extrapolated to the nuclear profile characteristics in non-Hodgkin's lymphoma.

Cell Nucleus↗
PubMed1975

[Measurement of nuclear size in cells from embryonic mouse brain in monolayer culture using automatic image analysers].

Size analyses and size classifications were made of the nuclei of embryonal mouse brain cells in monolayer culture. Measurements were made by surface analysis, using the Quantimet (1,299 nuclei), and linear analysis, using the Digiscan (1,887 nuclei). Despite the different methods of measurement and different logarithmic classification, similar distribution curves were obtained, approaching the Gaussian normal distribution. The methodical problems of karyometry as well as the problems of statistical data processing are discussed.

Animals↗
PubMed2002

An example of complex modelling in dentistry using Markov chain Monte Carlo (MCMC) simulation.

BACKGROUND: In the usual regression setting one regression line is computed for a whole data set. In a more complex situation, each person may be observed for example at several points in time and thus a regression line might be calculated for each person. Additional complexities, such as various forms of errors in covariables may make a straightforward statistical evaluation difficult or even impossible. OBJECTIVE AND METHOD: During recent years methods have been developed allowing convenient analysis of problems where the data and the corresponding models show these and many other forms of complexity. The methodology makes use of a Bayesian approach and Markov chain Monte Carlo (MCMC) simulations. The methods allow the construction of increasingly elaborate models by building them up from local sub-models. The essential structure of the models can be represented visually by directed acyclic graphs (DAG). This attractive property allows communication and discussion of the essential structure and the substantial meaning of a complex model without needing algebra. EXAMPLE: After presentation of the statistical methods an example from dentistry is presented in order to demonstrate their application and use. The dataset of the example had a complex structure; each of a set of children was followed up over several years. The number of new fillings in permanent teeth had been recorded at several ages. The dependent variables were markedly different from the normal distribution and could not be transformed to normality. In addition, explanatory variables were assumed to be measured with different forms of error. Illustration of how the corresponding models can be estimated conveniently via MCMC simulation, in particular, 'Gibbs sampling', using the freely available software BUGS is presented. In addition, how the measurement error may influence the estimates of the corresponding coefficients is explored. It is demonstrated that the effect of the independent variable on the dependent variable may be markedly underestimated if the measurement error is not taken into account ('regression dilution bias'). CONCLUSION: Markov chain Monte Carlo methods may be of great value to dentists in allowing analysis of data sets which exhibit a wide range of different forms of complexity.

Bayes Theorem↗
PubMed1991

Body temperature in apparently healthy African children under 10 years of age.

Body temperature was determined weekly for a period of 3 weeks in 346 healthy children aged 5 months to 10 years. Individual axillary temperatures in the 346 children ranged from 35.05 degrees C to 37.28 degrees C and fell into normal distribution curve. This study has thus determined normal body temperatures in Nigerian children and will serve as reference data for future comparison.

Axilla↗
PubMed1988

[Application of logistic curve fitting to cell-mediated cytotoxicity tests].

Blood mononuclear cells from 6 healthy adults were examined for LAK activity against 16 cell lines derived from human malignant tumors. The cytotoxicity curves obtained from a linear plot of the log of E/T ratio versus the percentage of the target cells killed were found to well fit the logistic curves. As the logistic distribution is known to approximate to the normal distribution, and the K/2 value is the function value for the representative, the K/2 value is reasonably selected as the % lysis value for the lytic unit calculation. Values of the three parameters, K as the maximum cytotoxicity, A as the scale parameter and B as the shape parameter, were analyzed using the experimental data. Eleven targets had three or more significantly fitted curves. Six among them were selected as highly sensitive cell lines to LAK activity, because the average values for K were higher than 80% (coefficients of variation were from 0.02 to 0.11) and analyzed further. The average values for B were relatively constant (range: 1.09-1.56) and the average values for A varied from 3.5 to 20.3 (conefficients of variation were from 0.26 to 0.71). The shape of the curves were nearly the same. These results indicate that the 6 cell lines are useful as the targets for the LAK activity.

Cytotoxicity Tests, Immunologic↗
PubMed1984

Plasminogen activator activity in human breast cancer cytosols.

Plasminogen activators are an enzyme complex which first appears in the trophoblast and may contribute to the invasive and metastatic process in neoplastic growth. In this study, 102 cytosols from human breast cancer biopsies were analyzed for PAA (with the chromogenic tripeptide S2251 KABI), steroid receptors (ER and PR), age, nodal and menopausal status. The data were submitted to log (X + 1) transformation and the raw and transformed data were analyzed for distribution. Because of the largely non-normal distribution of the data, Spearman's rank order correlation coefficients were generated to test for relationships between these differentiation markers and the clinical data. Nodal and menstrual status groups were compared for PAA and receptor levels using the Wilcoxon rank sum test. We found significant positive correlations between net PAA and ER (p = 0.0001), net PAA and PR (p = 0.0001), and net PAA and age (p less than 0.05). PAA levels for nodal status groups were found to be significantly different (negative at p less than 0.05). Nodal metastases predict poor prognosis while higher receptor levels indicate a better prognosis. As PAA levels correlate with the above biologic properties of breast tumors, they may provide additional prognostic information, especially in cases in whom auxiliary node status is unknown.

Breast Neoplasms↗
PubMed1998

[Use of the Purdue Non-verbal Test in a group of candidates for a driving license].

The Purdue nonverbal test (PNT) was used to analyze intellectual abilities of 500 candidates for a driving license. The candidates were divided in five age groups of 100 subjects in each: 16-19, 20-24, 25-39, 40-54, and over 54. The distribution of result differs greatly from the normal distribution (P < 0.01) for all age groups of candidates. The distribution of the results of the candidates over 54 is positively asymmetric, while the distribution of the results of all other age groups is negatively asymmetric. These results suggest that the PNT is poor in discrimination. The percentage of candidates categorized according to the PNT as "capable for handling a motor vehicle" was higher than expected, while the percentage of candidates categorized as of "limited capability" was below expectations. According to these criteria, no candidate was found "incapable", which is in sharp nonconformity with the expected 5 per cent (5%). The above results indicate that the screening of candidates according to the criteria of intellectual ability is inadequate because of inadequate criteria, especially those which are supposed to determine borderline and lower intellectual ability. The results of the research show that admission of candidates whose intellectual ability borders or is below intellectual insufficiency parameters renders inadequate the prevention of risks in traffic. The risk in traffic is expected to increases with every single driving license issued to a person whose intellectual ability is inadequate for safe driving.

Adolescent↗
PubMed1991

Estimating departure from normality.

Departure of a sample from a normal distribution should be assessed by a quantity that is meaningful in terms of the data, rather than merely by the P-value from a test statistic. Indices of departure based on the Shapiro-Francia W' and the Shapiro-Wilk W statistics are derived, and shown to have a natural interpretation in relation to the normal probability plot. A new diagnostic plot is proposed. An example is given which shows the relationship between one of the new indices and errors in calculated reference ranges due to non-normality of the data.

Adult↗
PubMed2000

[Normal and abnormal daily variability of urinary excretion of albumin].

Urinary albumin excretion (UAE) is very variable from day to day. We analyzed day-to-day UAE in 207 elderly (60-75 years) inpatients (134 with and 73 without diabetes mellitus) attending the department of internal medicine of the Angers University hospital. Twenty-four-hour urine was collected 3 times during a 5-10 day hospitalization period. One-hundred-fifty-one patients (73%) displayed normoalbuminuria (UAE < 30 mg/24 h in 2 or 3 measures) while 56 patients (27%) had microalbuminuria (UAE within 30-300 mg/24 h in 2 or 3 measures). As the raw data of UAE was not normally distributed, we transformed UAE into the variable z = log(log(k+ UAE)) where k is an integer. We found that z has a gaussian distribution for k = 2. Mean value and coefficient of variation of z in the 3 measurements were used to define the level and the temporal intra-individual variability of UAE. Expressed in term of z, the day-to-day intra-individual variability of UAE showed a potent change (from large variability to small variability) at the particular level z = 1.25, corresponding to UAE = 30.8 mg/24 h, which is precisely the level currently used to define microalbuminuria in diabetic subjects.

Aged↗
PubMed1994

On a truncation-flexible repeated significance test.

A repeated significance test for the mean of a normal distribution with guaranteed Type I error rate not depending on the truncation point is presented. The type of design has the advantage that it may be applied to define a sequential test based on accumulating data, applicable to a wide range of variables of which the fixed-sample-size test would have been based on the standard normal, without the requirement that the covariance structure of the sequence by computed explicitly. The test is shown to be especially convenient for certain types of ongoing survival studies, and for the problem of testing for differences in means or proportions, and appears to have operating characteristics similar to those of standard repeated significance tests with corresponding truncation points.

Biometry↗
PubMed1997

Precise gaussian distribution functions of maternal serum alpha-fetoprotein and free beta-subunit of human chorionic gonadotropin for trisomy 21 screening: improved accuracy for patient counseling.

OBJECTIVE: Gaussian equation curves are used to generate baseline curves against which a priori maternal age Down syndrome risks are adjusted to develop likelihood ratios for individual patients. We sought to evaluate the accuracy of these calculations, minimize the affects of outliers, and to make improvements. STUDY DESIGN: Gaussian distribution functions were used to investigate the best model for alpha-fetoprotein and free beta-human chorionic gonadotropin multiples of the median with use of nonlinear regressions. Parameters from distribution functions can be used to compute a more precise likelihood ratio for the decision logic for trisomy 21. A total of 58,297 normal cases and 348 cases of trisomy 21 were computed. RESULTS: Log normal distribution functions generated by nonlinear regression produced excellent but exaggerated goodness of fit R2 to the frequency distributions of the data. For normal cases values were as follows (in mean, SD, and R2, respectively): log alpha-fetoprotein -0.07199, 0.15681, and 0.9970; log beta-human chorionic gonadotropin -0.15203, 0.24284, and 0.9987. For trisomy 21 cases the values were (in mean, SD, and R2, respectively) for log alpha-fetoprotein -0.19303, 0.15802, and 0.9828 and for log beta-human chorionic gonadotropin 0.19996, 0.29760, and 0.9669. Distributions reconstructed with use of statistical means and SDs generated goodness of fit R2 from 0.585 to 0.914. Use of means and SDs derived from distribution functions increased the R2 to 0.855 and 0.999. The change in the model produces, at a 5% false-positive rate, a sensitivity of 57.18% (199/348). A 1 in 113 cutoff point risk is obtained and is tighter than the 1 in 251 without the distribution functions, as versus 1 in 270 by age calculations alone. CONCLUSIONS: Our data suggest that (1) normality of log transforms of alpha-fetoprotein and normality of log transforms of beta-human chorionic gonadotropin are reasonable models, (2) distribution functions can minimize the effect of outliers, which produces more realistic risk estimates, and (3) the effect of distribution functions versus standard mean and SDs cannot automatically be extrapolated to other parameters, which must be tested individually.

Chorionic Gonadotropin, beta Subunit, Human↗
PubMedDate not supplied

A simulation model to estimate a distribution of lipid intake from breast milk during the first year of life.

This article brings together data on the proportion of mothers who breastfed their newborn infants, the duration of breastfeeding, infants' intake of breast milk, and the lipid content of breast milk, and presents a simulation model that estimates a distribution of lipid intake from breast milk during the first year of life. The simulation results may be translated into two assumptions useful for public health risk assessments. First, at any given time, approximately 22% of infants under one year are being breastfed; the remaining 78% have no exposure to chemicals via their mothers' breast milk. Second, lipid intake for the nursing infants may be characterized by a normal distribution with a mean of 26.81 g/day and a standard deviation of 7.39 g/day. In combination with measured or estimated concentrations of chemicals in the fat of breast milk, this distribution is suitable for estimating nursing infants' exposures to lipophilic chemicals. These results are based on data for probability and duration of breastfeeding which were standardized to the United States population, and on data for lipid intake from a sample of white, middle- to upper-income, highly educated women living in or near Davis, California.

Breast Feeding↗
PubMed1992

Intrahepatic portal venous variations: prevalence with US.

A prospective ultrasound study was undertaken to determine the prevalence of variants of the intrahepatic branching of the portal venous system. Of the 507 patients examined, 55 (10.8%) had trifurcation, 24 (4.7%) had a right posterior segmental branch arising from the main portal vein, 22 (4.3%) had a right anterior segmental branch originating from the left portal vein, and one (0.2%) had absence of the horizontal segment of the left portal vein. Not one patient had complete absence of the right portal vein in this series. The remaining 405 (79.9%) patients had normal distribution of the portal venous system; some patients of the normal group had minor variations in distribution.

Humans↗
PubMed2002

[Distribution of rat facial motoneurons and its reorganization following nerve reinnervation].

OBJECTIVE: To examine the distribution of rat facial motoneurons contributing different branches under normal situation and when nerve reinnervation occurred following facial nerve axotomy. METHODS: The normal distribution of motoneurons innervated both buccal and marginal mandibular branches and its reorganization after facial nerve reinnervation was observed using retrograde labeling with fluorescein. RESULTS: Under normal situation, the motoneurons contributing buccall and marginal mandibular branches were primarily distributed in the intermedial and lateral subnucleus in facial nucleus and almost completely overlapped. The two types labeled neurons organized closely, but there were no double-labeled neurons. Although the motoneurons contributing buccall and marginal mandibular branches were primarily overlapped 4 month post-anastomosis, the number of the labeled neurons obviously decreased and the organization got more scattered. There were 10% of buccall branches, 5% of marginal mandibular motoneurons in the dorsal subnuleus, 1% of buccall and 4% of marginal mandibular in dorsal ventral and medial subnucleus. The distribution pattern of the motoneurons 6 month post-anastomosis was similar to that of 4 month post-anastomosis, but the number of the labeled neurons increased, and there were 1%-2% double-labeled neurons. CONCLUSION: The distribution pattern of motoneurons innervated both buccal and marginal mandibular branches indicates that it should exist wide-spread communicating branches, and its reorganization after facial nerve reinnervation suggests that misdirected regeneration occurs among motoneurons innervating different branches.

Animals↗