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PubMed1992

Calcitonin gene-related peptide, substance P and GAP-43/B-50 immunoreactivity in the normal and arthrotic knee joint of the mouse.

The aim of this study was to describe the normal distribution of calcitonin gene-related peptide (CGRP) and substance P (SP) containing fibres in the knee joint of the mouse and to obtain insight into the changes in innervation associated with degenerative processes in the joint. Arthrosis was induced by a single subpatellar intra-articular injection of bacterial collagenase. After decalcification in EDTA solutions, the CGRP and SP fibres were visualized by peroxidase-antiperoxidase pre-embedding immunocytochemistry for light microscopy. Control experiments on the mouse brain as a reference for the effect of EDTA on the immunostaining showed that the decalcification procedure with EDTA had not impaired the immunostaining. A rich innervation of thin varicose CGRP and SP immunoreactive fibres was found in most peri- and intra-articular tissue components. The periosteum, synovial tissues, the joint capsule and the intra-articular fat tissues were richly innervated. Less intense innervations were also found in the subchondral bone plates of the tibio-femoral joint and of the patella. Fibres were also found in the soft tissues between the patellar tendon and the femoral groove. No differences could be found between the location of CGRP and SP fibres with respect to the localization in the joint, but generally more CGRP fibres were found. The collagenase-induced osteoarthrosis was characterized by sclerosis of the subchondral bone, patellar dislocation, osteophyte formation, synovial proliferation and by severe cartilage abrasion, particularly on the medial side of the femoro-tibial joint. The overall distribution of CGRP and SP fibres was the same as in the control joints. However, major differences were found in all studied joints at specific locations around the cruciate ligaments, in the synovium around the patella, in the soft tissues lateral of the patella and in plica tissue between the patella and femoral groove. The CGRP and SP innervation was no longer detectable by immunolabelling with the antibodies. With a polyclonal antibody to the growth associated protein GAP-43/B-50, signs of degenerated axonal profiles were observed in these locations. At other peripheral locations, such as the muscles, the GAP-43/B-50 distribution was normal. In conclusion, the present study provides detailed information on the localization of CGRP and SP fibres, which may be involved in pain perception. Knowledge of the changes that occur during arthrosis may give more insight into the clinical symptoms.

Animals↗

PubMed1984

Heavy metals at trace level in edible mussels (Mytilus galloprovincialis Lamarck) from the gulf of Trieste.

The concentration of heavy metals (cobalt, nickel, copper, cadmium, mercury and lead), which are present at trace levels in the edible part of mussels (Mytilus galloprovincialis Lamarck) from hatcheries in the gulf of Trieste, is normally or log-normally distributed, according to a statistical test sensitive to asymmetry of the distribution. A log-normal distribution appears valid for describing nearly all trace metals, in particular toxic heavy metals like cadmium, mercury and lead. The frequency distribution of these metals has nearly the same asymmetry, although the one-way analysis of the variance shows that sample means come from different population means characterising the particular hatchery.

Animals↗

PubMed1998

Illness duration and neuropsychological impairments in schizophrenia.

This study aims to verify whether cognitive disturbances in schizophrenic patients are associated with illness duration, and to examine the influence of other covariates on neuropsychological disturbances. Sixty-nine consecutive admissions of schizophrenic patients (DSM-III-R, APA, 1987) were included to an acute psychiatric unit. Patients were evaluated by a semistructured interview and assessed with the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS). A wide neuropsychological battery, adapted to Spanish, was used. Variables were transformed to z-scores when their distribution was normal, or to log-values in the case of non-normal distributions. Pearson's correlation coefficients with a Bonferroni correction showed strong relationships between illness duration and cognitive performance in neuropsychological tests on visuomotor processes and delayed visual memory. In order to examine the influence of potential covariates on neuropsychological disturbances, stepwise multiple regression procedures were performed with each neuropsychological measure as a dependent variable, and years of education, age, gender, neuroleptic does in chlorpromazine equivalents, biperidene doses and illness duration as independent variables. The longer the illness duration, the poorer the performance on visuomotor process and delayed visual memory tasks. Moreover, the neuropsychological disturbances associated with illness duration were different from those related to aging, educational background, gender and treatment status. These findings suggest the existence of a relationship between cognitive decline in visuomotor and delayed visual memory functions and the length of schizophrenic illness.

Adolescent↗

PubMed2000

Intestinal trehalase activity in a UK population: establishing a normal range and the effect of disease.

Trehalose is a disaccharide, the main dietary source being mushrooms. It has been approved as an additive in the preparation of dried food. Isolated intestinal trehalase deficiency is found in 8% of Greenlanders, but is rare elsewhere. The normal range of trehalase activity and the incidence of isolated trehalase deficiency in the UK have not been reported. Patients (n 400) were investigated for suspected malabsorption. Endoscopic distal duodenal biopsies were taken for histological assessment and maltase, sucrase, lactase and trehalase estimation. Disaccharidase activities were determined by Dahlqvist's technique (Dahlqvist, 1968). Most patients (n 369) had normal duodenal histology. In these, square root transformation of trehalase activity produced a normal distribution. The normal range (mean +/- 2 SD) was 4.79-37.12 U/g protein. One patient had an isolated borderline trehalase deficiency. The thirty-one patients with villous atrophy had significantly reduced disaccharidase activities. With ingestion of a gluten-free diet, maltase, sucrase and trehalase activities recovered to normal in most patients, whereas lactase activity did not. The normal range and very low incidence of isolated enzyme deficiency is comparable with that described in populations from the USA and mainland Europe. Activity is significantly reduced in untreated coeliac disease and recovers with treatment with a gluten-free diet. There is no place for routine determination of trehalase activity in the UK population and there should be no concern over the introduction of trehalose-containing dried foods.

Adolescent↗

PubMed1979

Control chart for urinary oestriol excretion during pregnancy.

Calculations to define the distribution of normal urinary oestriol excretion values during pregnancy are presented. The values had a normal distribution, uniform variance and increased linearly with time after logarithmic conversion. The variance could, therefore, be partitioned and a control chart constructed.

Analysis of Variance↗

PubMed1993

Lung volume changes during relatively fluent speech in stutterers.

We investigated breathing patterns in stutterers during relatively fluent speech and compared these with normal subjects for similar speech tasks. Rib cage and abdominal displacements and esophageal, gastric, and transdiaphragmatic pressures provided indexes of diaphragmatic, rib cage, and abdominal muscle contraction. We found that stutterers spoke either at substantially higher or lower lung volumes than normal subjects, confining their speech to the inspiratory capacity or expiratory reserve volume. During spontaneous speech, stutterers did not cross functional residual capacity (FRC) for most breaths. In addition, stutterers used several different motion pathways from breath to breath. At high lung volumes stutterers used the diaphragm to provide inspiratory braking. At lung volumes below FRC stutterers recruited their abdominals. This contrasted with normal subjects who spoke in the middle part of the vital capacity and who recruited inspiratory and expiratory rib cage muscles above and below FRC, respectively. Breath sizes were log-normally distributed in stutterers compared with a gaussian distribution in normal subjects (P < 0.001). During reading, stutterers tended to cross FRC (P < 0.01), used very similar initiation lung volumes from breath to breath (P < 0.001), and used similar motion pathways to achieve deflation. We conclude that stutterers sustain fluency by speaking at abnormally high or low lung volumes and that this may account for the different muscle patterns observed in stutterers compared with normal subjects.

Diaphragm↗

PubMed1977

Osteoclast counting in crista biopsies.

A description is given of a modified method of counting osteoclasts both per section area and also relative to the remaining trabeculae surface area in crista biopsies. The material consisted of normal individuals, patients with clinical osteoporosis, and patients with chronic renal failure undergoing haemodialysis. The number of osteoclasts in the biopsies from normal and osteoporotic individuals showed a normal distribution with the same mean. In the haemodialysis patients there was a marked skew distribution. In normal individuals, there was a significant decrease in the number of osteoclasts per section area with age, but this was not significant when calculated relative to the bone surface area.

Adolescent↗

PubMed1985

Quantitative analysis of ultradian luteinizing hormone secretion in normal men.

Basal pulsatile secretion of luteinizing hormone (LH) was studied in 8 healthy adult men and analyzed by mathematical and statistical techniques. LH pulses previously defined by semiquantitative criteria resisted the data-smoothing techniques employed. LH values were shown to have normal distribution in normal men. No correlation was found between mean LH and testosterone levels for the same individual. On the basis of analysis of variance it was shown that the individual variability and not the collection time is important in determining each isolated LH value. The LH levels were located within a particular channel for each individual for each collection time.

Activity Cycles↗

PubMedDate not supplied

Fetal hemoglobin biosynthesis in clonal cell culture.

Availability of the clonal erythropoietic cell culture methods provided a unique opportunity to study human hemoglobin biosynthesis under controlled conditions. Observations in several laboratories during the last four years fundamentally agree and can be summarized as follows: (1) Biosynthesis of fetal hemoglobin (HbF) is markedly augmented in cultures of adult erythropoietic precursors. (2) HbF biosynthetic capabilities inversely parallel the maturational stages of adult erythropoietic precursors in the marrow. (3) Adult circulating precursors (BFU-e) are also capable of augmented HbF biosynthesis in culture. (4) The pattern of Hb synthesized by fetal erythropoietic precursors corresponds very closely to the Hb compositions in the mature erythrocytes of the donors. (5) Burst-promoting activities (BPA) rather than erythropoietin (Ep) appear to stimulate HbF biosynthesis by augmentation of proliferation of precursors which are programmed to produce F cells in vivo. (6) Individual BFU-e are heterogeneously committed to HbF biosynthesis and their frequency distributions reveal normal distributions. (7) Increase in HbF production in culture is primarily due to increased production of the number of cells containing Hbf. (8) Commitment to produce HbF continues during subcolony formation in culture. (9)HbF synthesized in culture of adult and umbilical cord blood BFU-e reveal "adult" and "intermediate" values of G gamma:A gamma ratios, respectively. (1)) Frequency distributions of individual bursts varying in relative G gamma synthesis (G gamma/[G gamma+A gamma]) reveal unimodal distributions. (11) Positive correlations exist between gamma/(gamma+beta) and G gamma/(G gamma + A gamma) values in individual bursts.

Bone Marrow↗

PubMed1983

Microregional blood flow and high energy phosphates under conditions of high O2 supply in left ventricular subendocardium.

Blood flow and high energy phosphate (HEP) content were determined simultaneously in multiple microregions of the left ventricular subendocardium in 49 anaesthetized open-chest rabbits, to determine the relationship between the parameters during high O2 supply with hypercapnia and chromonar treatment. ATP and CP content were quantitated in quick-frozen hearts by fluorometry in 1-2 mg sites where perfusion was measured by H2 clearance employing bare-tipped platinum electrodes. Both hypercapnia and chromonar elevated subendocardial tissue perfusion approximately 30% and O2 supply 45% above control. Blood flow was normally distributed with either treatment, but was more homogeneous with hypercapnia. Neither treatment altered absolute levels of either HEP, but the variance of ATP was less than control. CP distribution was normal in both treatments. There was no significant linear correlation between blood flow and HEP under hypercapnia or chromonar treatment. We conclude that tissue HEP content is a variable not only dependent on O2 supply and blood flow, but also on the size of the ATP and CP pool and the energy demand of the local microregion. The variability of ATP in microregions of the rabbit subendocardium is reduced under conditions of high O2 supply.

Adenosine Triphosphate↗

PubMed1983

A simple method for the approximation of the behaviour of marker constituents in density-fractionated red blood cells by means of normalized cumulative distribution functions.

The present paper proposes a mathematical approach for the approximation of the relation between the concentration (or activity) of a cell constituent and the cumulative red cell distribution after density gradient centrifugation by means of normalized cumulative distribution functions (NCDF). With only one parameter (easily obtained on a programmable pocket calculator) and the mean concentration of the substance in the total red cell population this functional relation can be described in good approximation. The goodness of fit expressed by v2 (= square of correlation coefficient) to the experimentally obtained data is demonstrated for the cell constituents creatine (v2 = 0.85-0.97), RNA (v2 = 0.82-0.87) and G-6PD (v2 = 0.60-0.95). The method of NCDF is shown to be superior to an exponential function. It permits the estimation of a concentration (or activity) of a cell constituent for any chosen density-fractionated cell portion and thus gives information on the ratio of standardized portions of young: old cells.

Cell Separation↗

PubMed1995

Antiphospholipid antibodies in a healthy population: methods for estimating the distribution.

OBJECTIVE: To determine the distribution of antibodies to cardiolipin (IgG, IgM and IgA) in a healthy population. To classify subjects according to a cutpoint in order to determine what level of antibody measurement would yield 95% specificity. METHODS: Antiphospholipid (aPL) antibodies were measured using a conventional ELISA technique, with isotype specific antibody, to determine levels of IgG, IgM and IgA binding to cardiolipin. The subjects were 282 Red Cross blood donors, 82 undergraduate medical and nursing students, and 13 laboratory volunteers. RESULTS: The distribution of aPL antibodies measured in units of optical density is significantly skewed, while the distribution of aPL antibodies measured on the log scale is nearly symmetric. Neither distribution is normally distributed. There was no evidence that aPL antibodies differed significantly by age (up to age 50) or sex. We estimate the 90th, 95th, and 99th percentiles for IgG, IgM and IgA antibodies for the optical densities and binding indices. CONCLUSION: For 95% specificity we conclude that an adjusted IgG optical density above 0.386, an adjusted IgM optical density above 0.301, or an adjusted IgA optical density above 0.085 be considered positive.

Adult↗

PubMed1995

Statistical considerations regarding the use of ratios to adjust data.

OBJECTIVE: The use of ratios to adjust data (i.e. 'index' variables) is common in obesity and related research. The rationale for the use of ratios often seems to be the desire to control or eliminate the influence of the variable in the denominator. The purpose of this paper is to gain a greater appreciation of the statistical assumptions underlying ratios and their impact on data interpretation. RESULTS: We demonstrate the limitations of the indiscriminant use of ratios to adjust data. Specifically, we show that: (1) given linearity, a zero intercept between the numerator and denominator are necessary and sufficient conditions for a ratio to remove the confounding effects of the denominator; (2) seemingly minor departures from a zero intercept can have major consequences on the ratio's ability to control for the denominator; (3) the ratio of two normally distributed variables cannot be normally distributed, and this may violate the assumptions of subsequent parametric statistical analyses; (4) the use of ratios affects the error distribution of the data which may also violate the assumptions of subsequent parametric statistical analyses; (5) the use of ratios cannot easily take nonlinear effects between the numerator and denominator into account; (6) the use of ratios can introduce spurious correlations among the ratios and other variables; (7) the use of ratios can create interpretive difficulties. We also clarify that the mean of ratios is not necessarily equivalent to the ratio of the means of the numerator and denominator. Finally, we present and discuss formulae for the reliability of ratios and residuals. CONCLUSION: Because of the above issues, we question the indiscriminant use of ratios and advocate that investigators consider regression-based approaches as alternatives.

Body Constitution↗

PubMed1988

HLA DR and DQ distribution in normal human ocular structures.

HLA DR and DQ distribution was investigated in normal human ocular tissues, together with class I antigens and immunocompetent cell subsets, by immunofluorescence and immunoperoxidase procedures. In the anterior segment, our findings, consistent with those of previous reports, showed the wide distribution of class I antigens, specially in the corneal epithelium, while class II antigens were restricted to very rare cells scattered in the conjunctiva, the peripheral cornea and the stroma of the ciliary processes. Some non pigmented epithelial cells of the ciliary processes were HLA DR and DQ positive. In the posterior segment, class I antigens were abundantly represented in the choroid and the retinal layers. Few HLA DR and DQ positive cells were seen in the choroid, similar to those found in the anterior segment. Normal RPE did not react with any monoclonal antibody, but numerous cells located in the retina were strongly HLA DR and DQ positive, all around the blood vessels, and not at the sites of endothelial cells. The characterization of those cells, which could be hypothetized as pericytes needs further studies but suggests close relationships between neuroretina and the immune system. This study may provide insight in the implication of the immune system in many poorly understood ocular diseases.

Adult↗

PubMed1996

On modeling longitudinal pulmonary function data.

In this paper we have discussed how random effects can be included in linear models to accommodate the analyses of longitudinal pulmonary function (REM) and categorical (GEE) types of respiratory data. It was suggested that REM analysis be used for continuous observations that are normally distributed or that can be transformed to have near normal distributions and that GEE be used for categorical or non-normally distributed data. Two methods were reviewed, parallel plots and within-subject regression fitting, which can assist in determining the order of random effects to be included. Using a sample data set of longitudinal FEV1 measures, we outlined the steps that should be taken for selecting the within-subject error structure, the order of random effects, elements of the between-subject covariance matrix, and selecting the most important or predictive fixed effects. Lastly, two different types of residual plots were illustrated, conditional and marginal, which can be used to detect outliers and possible trends from underfitting the observed data. All options discussed herein are not available in all the programs currently available for doing the REM and GEE modeling.

Computer Simulation↗

PubMedDate not supplied

Theophylline tissue partitioning and volume of distribution in normal and dietary-induced obese rats.

Theophylline tissue distribution was examined in normal and dietary-induced obese Sprague-Dawley rats following constant infusion to steady-state. Theophylline distribution was linear among all tissues and uniform throughout body water spaces. The apparent distribution coefficient, Kd,app (tissue: serum concentration) ranged from 0.55 to 0.69 for all lean tissues, but averaged 0.08 in fat. Obese rats had a consistently higher Kd,app in several tissues including muscle, heart, and liver caused by reduced (from 42 to 33 per cent) serum protein binding. Muscle slice uptake of theophylline from buffer was similar in normal and obese animals, confirming serum binding as the factor altering Kd,app. The conceptual and applied bases of calculating and measuring steady-state volume of distribution (VSS) by various methods were explored. The physiological perturbations of theophylline VSS by obesity can be accounted for by alterations in serum binding and expanded lean and fat tissue masses, rather than changes in tissue partitioning.

Animals↗

PubMed1988

Simulated percentage points for the null distribution of the likelihood ratio test for a mixture of two normals.

We find the percentage points of the likelihood ratio test of the null hypothesis that a sample of n observations is from a normal distribution with unknown mean and variance against the alternative that the sample is from a mixture of two distinct normal distributions, each with unknown mean and unknown (but equal) variance. The mixing proportion pi is also unknown under the alternative hypothesis. For 2,500 samples of sizes n = 15, 20, 25, 40, 50, 70, 75, 80, 100, 150, 250, 500, and 1,000, we calculated the likelihood ratio statistic, and from these values estimated the percentage points of the null distributions. Our algorithm for the calculation of the maximum likelihood estimates of the unknown parameters included precautions against convergence of the maximization algorithm to a local rather than global maximum. Investigations for convergence to an asymptotic distribution indicated that convergence was very slow and that stability was not apparent for samples as large as 1,000. Comparisons of the percentage points to the commonly assumed chi-squared distribution with 2 degrees of freedom indicated that this assumption is too liberal; i.e., one's P-value is greater than that indicated by chi 2(2). We conclude then that one would need what is usually an unfeasibly large sample size (n greater than 1,000) for the use of large-sample approximations to be justified.

Biometry↗

PubMed2001

Hair density, hair diameter and the prevalence of female pattern hair loss.

BACKGROUND: Female pattern hair loss is common but estimates of its prevalence have varied widely. The relationships between the clinical diagnosis of female pattern hair loss and objective measurements of hair density and hair diameter have not previously been evaluated. OBJECTIVES: To determine the prevalence of female pattern hair loss and to relate the clinical findings to hair density and hair diameter. METHODS: We examined 377 women, aged 18--99 years, who presented to a general dermatology clinic with complaints unrelated to hair growth (the unselected sample). A second group of 47 women referred with typical female pattern hair loss was included in analyses of the relationships between hair density, hair diameter and the clinical diagnosis. Hair density was measured using a photographic method. In each subject the major and minor axis diameters were measured in a random sample of 50 hairs. RESULTS: Six per cent of women aged under 50 years were diagnosed as having female pattern hair loss, increasing to 38% in subjects aged 70 years and over. The mean +/- SEM hair density was 293 +/- 61.3 hairs cm(-2) at age 35 years, falling to 211 +/- 55.1 hairs cm(-2) at age 70 years. Hair density showed a normal distribution in the unselected sample. Most women classified as having female pattern hair loss had hair densities within the lower half of the normal distribution. The perception of hair loss was determined mainly by low hair density (ANOVA P < 0.001), but there was overlap in hair density between women classified as having Ludwig I hair loss and the no hair loss group, which was partly accounted for by differences in mean hair diameter (ANOVA P < 0.001). Low hair density was associated with fewer hairs of all diameters. CONCLUSIONS: Hair density in women is distributed as a normal variable, indicating that it is determined as a multifactorial trait. Women with female pattern hair loss have a hair density which falls below the mean but lies within the spectrum of the normal distribution, although other factors, including hair diameter, may affect the subjective impression of hair loss. The hair diameter data suggest that low hair density is not due to progressive diminution in hair follicle size and that follicular miniaturization may occur within the space of a single hair cycle.

Adolescent↗