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PubMed1997

Linear growth in early treated children with congenital hypothyroidism.

Length/height was studied from birth to 6 years of age in 103 children with congenital hypothyroidism identified by the Norwegian or Swedish screening programs. We used the "infancy-childhood-puberty (ICP) growth model". This model describes normal linear growth during the first 3 years of life by an infancy component with the addition of a childhood component, the latter acting from the second half of the first year. In comparison with reference children, children with hypothyroidism had reduced growth from 6 to 12 months, and increased growth after 12 months of age. Mean onset of the childhood component of growth was delayed from 8.1 months (SD 1.9) to 10.4 months (SD 2.2) in girls, and from 8.9 months (SD 2.0) to 11.0 months (SD 2.1) in boys. Age at onset of the childhood component was correlated with age at start of treatment (r = 0.24), and in children with more severe hypothyroidism (pretreatment serum thyroxine < 40 nmol/l) inversely correlated with the L-thyroxine dose at start of treatment (r = -0.40). Change in height standard deviation score from 1 to 3 years of age was correlated with the serum thyroxine concentration at age 1 year (r = 0.30). The delay in the onset of the childhood component of growth and the association with age at start of treatment and initial L-thyroxine dose indicate that thyroid hormones during the first months of life are essential for normal onset of the childhood component of growth, which otherwise is assumed to be growth hormone-dependent.

Age Factors↗

PubMed2002

Statistical procedures to test for linearity and estimate threshold doses for tumor induction with nonlinear dose-response relationships in bioassays for carcinogenicity.

Sublinear shapes of the dose-response curve in the low-dose range of toxicity testing are often postulated to be indicative of a no-effect threshold. We present statistical procedures to test sublinear dose responses in bioassays for carcinogenicity against the hypothesis of linearity and estimate a lower confidence limit for the dose at the postulated breakpoint. First, a control tumor incidence of 0 is assumed. Tumor incidence at dose 1 is allowed to range from 0 to 4 tumor-bearing animals (TBAs) in groups of 50 animals, dose 2 is assumed to result in a tumor incidence of 5-25 TBAs. The null hypothesis of a linear dose response is tested by (i) the likelihood ratio (LR) test and (ii) the minimum chi(2) (MC) method. Validation by simulation showed the MC method to be more conservative than the LR test. At the 5% level with MC, the following observed numbers of TBAs for the dose sequence 0-1-2 resulted in rejection of the hypothesis of linearity: 0-0-6, 0-1-10, 0-2-13, 0-3-16, 0-4-18. Second, the analysis was adapted to allow for a control tumor incidence of 0-4 TBAs/50 and a tumor incidence of 0-10 TBAs/50 at dose 1, and the minimum number of TBAs at dose 2 to reject linearity at the 5% level was calculated. Third, a program is made available to analyze data derived from protocols that include nonstandard dose span and group size. Internet access to the respective statistics software and source file is provided. Examples for nasal tumor induction by formaldehyde and for the induction of renal adenocarcinoma by ochratoxin A are shown. The proposed analysis may be useful to test sublinear sections of the dose response for the possibility of a threshold for carcinogens and to define dose levels that could be used as a starting point for setting exposure standards.

Adenocarcinoma↗

PubMed1986

Pharmacokinetics and metabolism of hexamethylmelamine in mice after IP administration.

The pharmacokinetics of hexamethylmelamine (HMM) and its first metabolite (hydroxymethylpentamethylmelamine: HMPMM) following IP bolus dose of 200 mg/kg were studied in mice. The drug concentrations were determined by a sensitive reversed-phase HPLC assay. Thus, for the first time, HMM major hydroxylated and demethylated metabolite plasma levels canbedetermined at the same time. Pharmacokinetic data were analyzed by an original method using a nonlinear cost function minimized by a simplex algorithm. An important property of this computer program is that convergence is ensured in contrast to linear or nonlinear least-square regression analysis, which leads to lack of convergence or to false convergence. Both HMM and HMPMM data fit a one-compartment open model. The parameters obtained indicate that the parent drug would probably be rapidly and completely transformed by the human body into HMPMM.

Algorithms↗

PubMed1997

Third order tooth movements with straight wire appliances. Influence of vestibular tooth crown morphology in the vertical plane.

1. The labial surface in the vertical plane was investigated in 3 sections: center, mesial, and distal edge of an ideally positioned bracket. The material consisted of 28 casts taken from 14 female and male individuals with a mean age of 26.8 years. 2. After trimming each cast, the resulting surface was photocopied, enlarged 8 times, then digitized under a 2.0 mm grid (corresponding to 0.25 mm of the original size). 3. Using a statistical computer program, mean curves including standard deviations and non-linear regression curves were calculated from the individual data. In accordance with their anatomy 3 groups of teeth were formed in each jaw: front teeth, premolars, and molars. The curves, including the comparison of the squared regression curves, provide an accurate mathematical description of the labial tooth crown in the above-stated sections. 4. The angle differentials between a reference tangent and 20 other tangents were calculated. From a practical standpoint, information is obtained on the extent to which the torque of a tooth would be changed if a bracket was to be positioned vertically (in 0.5 mm increments) from its ideal position. These changes of torque fluctuate on average between 1.3 degrees (mandibular front teeth) and 3.3 degrees (mandibular molars) for every 0.5 mm of vertical deviation. 5. The calculated comparisons of the curves permitted the construction of bracket bases filling-at least in the vertical dimension-the tooth surface most accurately in the "optimal" position.

Adolescent↗

PubMed1992

Calculation of antibody and antigen concentrations from ELISA data using a graphical method.

A graphical method for determining the concentration of either the antibody or the antigen from ELISA data is presented in the form of a GWBASIC program. In the program, ELISAEQ, optical densities (OD) obtained from a 96-well ELISA plate can be input either directly by interfacing a microplate reader to the computer or manually. The program uses standard sample data, and selects the semilogarithmic linear range. Over this range, a least-squares method is used to determine the concentrations of interest. In addition, a hyperbolic interpolation formula is derived over the entire range for estimating the antibody or antigen concentration of the unknown samples whose OD is beyond the linear range.

Antibodies↗

PubMed1993

High-performance liquid chromatographic separation of biogenic polyamines using 2-(1-pyrenyl)ethyl chloroformate as a new fluorogenic derivatizing reagent.

The application of a new fluorogenic pre-column derivatizing reagent, 2-(1-pyrenyl)ethyl chloroformate (PEOC), is reported for the separation and detection of biogenic polyamines using column liquid chromatography. The development of the method included the optimization of excitation and emission wavelengths, efficient gradient programming, derivatization temperature, time, and pH. Minimum detection limits, linear ranges, reproducibility, and recovery from analyzed samples were determined. The procedure was applied to hydrolyzed serum samples taken from healthy individuals and cancer patients. Separation of PEOC-derivatized polyamines from the serum hydrolysis by-products was successful and detection limits were more favorable than those previously reported for 9-fluorenyl-methyl chloroformate-derivatized polyamines.

Biogenic Amines↗

PubMed1972

Analysis of a calcium ion binding system composed of two different sites.

Using murexide (Mx), a metallochromic indicator, and a dual wavelength spectrophotometer with a high signal-to-noise ratio, the Ca(++) binding in a system containing two classes of binding sites was studied. Solutions with solute containing one or two classes of Ca(++) binding sites and without such solute were titrated with Ca(++) using Mx as an indicator of free Ca(++) concentration. Since curvilinear Scatchard plots are obtained from titration curves of solutes containing two classes of binding sites, a computer program was developed to resolve such plots into two linear partial plots, each corresponding to a single class of binding site. The validity of the procedure was examined with solutions of ethylene glycol bis(beta-aminoethyl)-N-N'-tetraacetic acid, adenosine triphosphate (EGTA, ATP), or a mixture thereof. The method was also applied to biological material and it was found that a protein fraction isolated from rat skeletal muscle sarcotubular membranes, termed Fraction-2 (Fr-2), has two classes of binding sites for Ca(++); the association constants of the high affinity site and low affinity site are 4.3 x 10(5) M(-1) and 9 x 10(3) M(-1), respectively. The advantages and limitations of this methodology are discussed.

Acetates↗

PubMed1999

Cadmium and lead in infant cereals--electrothermal-atomic absorption spectroscopic determination.

Because infant cereals are an important component of the infant diet from the fourth month of life onwards and therefore contribute to the dietetic intake of metals by infants, cadmium and lead were measured in samples of cereals commercially available in Spain. For this purpose an electrothermal atomic absorption (ET-AAS) method for determining cadmium and lead in these products was studied. The ET-AAS instrumental conditions and temperature/time furnace program were selected. The analytical parameters of the method (linearity, detection and quantification limits and precision) show its usefulness in measuring cadmium and lead in infant cereal products. The method was applied to eight different types of infant cereals from four different manufacturers, in all 29 different infant cereal products commercially available in Spain. The cadmium and lead contents of milk-free infant cereals range from 6.6 to 35.8 ng/g and from 36.1 to 305.6 ng/g, respectively, while the ranges corresponding to milk-added infant cereals are 2.9-40.0 ng/g for cadmium and 53.5-598.3 ng/g for lead. The cadmium and lead contents of cereal products of the same type from different manufacturers is responsible for the large confidence intervals and made it impossible to detect significant differences among the different products. Given the values found for lead and the correlation between chronic exposure to low lead doses and neuropsychological damage in early childhood, efforts should be made to reduce lead contamination.

Cadmium↗

PubMed1999

Effect of preflaring on Root ZX apex locators.

The Root ZX apex locator is an example of a generation of apex locators that identify the terminus of the canal by measuring a ratio between two electrical impedances. Studies have shown this device to have a high degree of accuracy. However, the manufacturer warns that the performance of these devices is limited by the presence of calcifications and dentinal shaving obstructions. An in vitro study was designed to determine if preflaring of canals would facilitate the passage of files to the apical foramen by eliminating cervical interferences and to see what effect this would have on the performance of the Root ZX apex locator. Thirty-two canals were divided into two groups. Group 1 was not manipulated before use of the Root ZX apex locator and served as control. In group 2, the canals were preflared before the use of the Root Zx apex locator. The working length files were secured in place and measured with the linear measurement tool used by the Visilog 5 imaging program. Results of this study suggest that preflaring of canals will allow working length files to more consistently reach the apical foramen (p = 0.015), which in turn increases the efficacy of the Root ZX apex locator.

Dental Instruments↗

PubMed1981

A computational procedure for the analysis of electron images of nucleic acid molecules.

A new procedure is described for analyzing electron images of labeled nucleic acid molecules. The method makes use of one-dimensional digital image information and determines the best relative orientation of the linear molecules. The analysis is performed with the computer program CLUSTER, which combines the information from each molecule stepwise in an iterative procedure, so that finally a label distribution is obtained, which is the combination of all information available. The rationale behind the analysis is the calculation of similarity coefficients, which are a measure of the probability for the relative orientation of each molecule pair. The method has been thoroughly tested and compared with other procedures described in the literature in order to indicate its performance and power. A biological application concerning the distribution of the protein RNA-polymerase on DNA of phage Mu is presented.

Bacteriophage mu↗

PubMed2000

Population pharmacokinetics of tiagabine in epileptic patients on monotherapy.

A retrospective study of the population pharmacokinetics of tiagabine was performed from sparse data collected in a multicentre clinical trial in patients with newly diagnosed partial seizures. The purpose was to estimate the inter patient variability and to study the influence of various demographic, environmental and pathophysiological parameters on the pharmacokinetics of tiagabine in patients on monotherapy. A total of 593 plasma concentrations from 130 patients dosed with 2.5, 5, 7.5 or 10 mg tiagabine twice daily were used for modelling. A one-compartment open model with first-order absorption and elimination was fitted to the concentration-time data using the NONMEM program. Selection of covariates was initially performed using stepwise linear regression analyses. The selected covariates were incorporated in the population model and the importance of each covariate was investigated by means of backwards elimination. A one-compartment model with first-order absorption and elimination adequately described the tiagabine concentration-time profile. The apparent clearance as well as the apparent volume of distribution were both significantly correlated to body height in a nonlinear relationship. No other demographic, environmental or clinical chemical parameters were identified as covariates although only a few pathological values of the latter were present in the data. The mean values of CL/f was 6.10 l/h, of V/f was 62.0 l and of k(a) was 1.25 h(-1) for a subject of 170-cm height. The population half-life was 5.72 h. The apparent clearance and volume of distribution of tiagabine in epilepsy patients on monotherapy were both dependent on body height. Prospective studies are required in order to reveal if dose adjustments based on body height will result in improved therapeutic outcome.

Adolescent↗

PubMed2003

Potential of mobile intraoperative radiotherapy technology.

Mobile IORT units have the potential to change the way patients who have cancer are treated. The integration of IORT into cancer treatment programs, made possible by the new technologies of mobile linear accelerators that can be used in unshielded operating rooms, makes IORT significantly less time-consuming, less costly, and less risky to administer. It is now practical for IORT to be used in early-stage disease, in addition to advanced disease, and in sites for which patient transportation in the middle of surgery is considered too risky. Preliminary results of trials for early-stage breast and rectal cancer indicate benefits of IORT. Pediatric patients and patients who have lung cancer, previously underserved by IORT therapies, can be offered potential gains when patient transport issues do not limit IORT. Furthermore, because many of these mobile systems require no shielding, it is now practical for mobile units to be shared between hospitals, making this new mobile technology much more widely available.

Adult↗

PubMed2002

Monte Carlo model of nonlinear chromatography: correspondence between the microscopic stochastic model and the macroscopic Thomas kinetic model.

The Monte Carlo model of chromatography is a description of the chromatographic process from a molecular (microscopic) point of view and it is intrinsically based on the stochastic theory of chromatography originally proposed by Giddings and Eyring. The program was previously validated at infinite dilution (i.e., in linear conditions) by some of the authors of the present paper. In this work, it has been further validated under nonlinear conditions. The correspondence between the Monte Carlo model and the well-known Thomas kinetic model (macroscopic model), for which closed-form solutions are available, is demonstrated by comparing Monte Carlo simulations, performed at different loading factors, with the numerical solutions of the Thomas model calculated under the same conditions. In all the cases investigated, the agreement between Monte Carlo simulations and Thomas model results is very satisfactory. Additionally, the exact correspondence between the Thomas kinetic model and Giddings model, when near-infinite dilution conditions are approached, has been demonstrated by calculating the limit of the Thomas model when the loading factor goes to zero. The model was also validated under limit conditions, corresponding to cases of very slow adsorption-desorption kinetics or very short columns. Different hypotheses about the statistical distributions of the random variables "residence time spent by the molecule in mobile and stationary phase' are investigated with the aim to explain their effect on the peak shape and on the efficiency of the separation.

Journal Article↗

PubMed2005

Observation of a one-dimensional adsorption site on carbon nanotubes: adsorption of alkanes of different molecular lengths.

Three well-defined adsorption sites have been found on opened single-wall carbon nanotubes by temperature-programmed desorption measurements for several alkanes. A series of linear chain alkanes from pentane to nonane, as well as a branched alkane molecule, 2,2,4-trimethylpentane, were used to elucidate the effect of molecular length on the capacity of the adsorption sites. The two highest-energy adsorption sites were assigned as the nanotube interior sites and groove sites on the outside of the nanotube bundles. Hybrid Monte Carlo simulations were performed to probe the molecular-level details of adsorption. Both in experiments and in the simulation, the groove sites were seen to behave as one-dimensional adsorption space, demonstrating an inverse dependence of capacity on the length of the adsorbed molecule. In contrast, the capacity of the internal sites was found to depend inversely on the volume occupied by the molecule.

Journal Article↗

PubMed2004

The treatment effect of mandibular protrusive appliances on the glenoid fossa for Class II correction.

A study was undertaken to determine the contribution of glenoid fossa modification in the correction of skeletal Class II malocclusions. Individually corrected lateral tomograms of 35 patients (18 boys and 17 girls) between the ages of 7.96 and 15.06 years were used. The subjects were selected on the basis of the criteria that they were suitable for treatment with a mandibular protrusive appliance (activator). The mean duration of activator treatment was 1.33 years. Tomograms were taken on a pre- and posttreatment basis. The tomograms were scanned and digitized on screen using a common software program. Points were located on each tomogram and specific linear measurements were used to evaluate any changes in glenoid fossa morphology. Paired t-tests were applied for the left and right sides separately and between the before and after treatment measurements. Paired t-tests were also applied between the left and right sides to test for any difference between the sides. The results of this study demonstrated that there are no positive radiographically depictable contributions from glenoid fossa modification for the correction of skeletal Class II malocclusions treated with mandibular protrusive appliances (activators). In addition, no statistically significant differences were found between right and left sides denoting relative symmetry. It is concluded that, contrary to animal research and magnetic resonance findings, it seems possible that glenoid fossa modeling is not induced by mandibular protrusive appliances during treatment of skeletal Class II problems.

Activator Appliances↗

PubMed2004

Cerebrovascular risk factors and clinical classification of strokes.

Cerebrovascular risk represents a progressive and evolving concept owing to the particular distribution of risk factors in patients with ischemic stroke and in light of the newest stroke subtype classifications that account for pathophysiological, instrumental, and clinical criteria. Age represents the strongest nonmodifiable risk factor associated with ischemic stroke, while hypertension constitutes the most important modifiable cerebrovascular risk factor, confirmed by a host of epidemiological data and by more recent intervention trials of primary (HOT, Syst-Eur, LIFE) and secondary (PROGRESS) prevention of stroke in hypertensive patients. To be sure, a curious relationship exists between stroke and diabetes. Although the Framingham Study, The Honolulu Heart Program, and a series of Finnish studies reported a linear relationship between improved glucose metabolism and cerebral ischemia, the clinical and prognostic profile of diabetic patients with ischemic stroke remains to be fully understood. Our group, on the basis of TOAST classification--a diagnostic classification of ischemic stroke developed in 1993 that distinguishes five different clinical subtypes of ischemic stroke: large-artery atherosclerosis (LAAS), cardioembolic infarct (CEI), lacunar infarct (LAC), stroke of other determined origin (ODE), and stroke of undetermined origin (UDE), and now extensively used in clinical and scientific context--analysed the prevalence of cerebrovascular risk factors and the distribution of TOAST subtypes in more 300 patients with acute ischemic stroke in two consecutives studies that reported the significant association between diabetes and the lacunar subtype and a better clinical outcome for diabetic patients, most likely related to the higher prevalence of the lacunar subtype. Well-confirmed are the roles of cigarette smoking, atrial fibrillation, and asymptomatic carotid stenosis as cerebrovascular risk factors. Particularly interesting seems to be the function of inflammation markers (CRP, TNF-alpha, IL-1 beta, ISPs) as potential risk factors. Still elusive remains the association between cholesterol serum levels and stroke, on the basis of the epidemiological data regarding this causative relationship, confirmed only by the results of intervention trials (4S, LIPID, CARE, HPS, ASCOT). Ultimately, cerebrovascular risk appears peculiar owing to the unique relationship between some modifiable risk factors (mainly diabetes and cholesterol) and the possible preferential association with stroke subtypes and specific cerebrovascular risks.

Albuminuria↗

PubMed1999

Craniofacial morphology in 6-year-old Icelandic children.

The purpose of the study was to describe the craniofacial characteristics of 6-year-old Icelandic children, make a normative standard for children with an Angle Class I molar relationship, and compare them to those with an Angle Class II molar relationship. The material consisted of the radiographs of 363 children, 184 (50.7 per cent) boys and 179 (49.3 per cent) girls with a mean age of 6 years 7 months (range: 5 years 7 months-7 years 8 months). Twenty-two reference points were digitized and processed by standard methods with the Dentofacial Planner computer software program. The 33 variables calculated included both angular and linear. Two sample t-tests were used to study the differences between different groups. Only minimal differences could be noted between sexes in sagittal and vertical angular measurements. Linear measurements, on the other hand, were usually larger for the boys. When compared with Norwegian material of the same age group, similar trends were observed between sexes in both studies, but the Icelandic children showed slightly more mandibular prognathism and a lower mandibular plane angle. When compared with children with an Angle Class I molar relationship, children with an Angle Class II molar relationship did not have a different maxillary prognathism nor a different mandibular length. Cranial base dimensions were all significantly greater and the cranial base flexure was also significantly more obtuse in the distal group.

Case-Control Studies↗

PubMed2004

Craniofacial skeletal and soft tissue morphology in Icelandic adults.

The purpose of the study was to describe the craniofacial characteristics of Icelandic adults on lateral skull cephalograms. The material consisted of 155 (47.8%) males and 169 (52.5%) females. The mean ages were 35.5 and 34.2 years, respectively. Twenty-two skeletal reference points and 11 soft tissue points were digitized and processed by standard methods with the Dentofacial Planner computer software program. The 45 variables calculated were both angular and linear. Two-sample t-tests were used to study the differences between sexes. Mandibular prognathism was significantly greater in males (P < or = 0.05), but the inclination of both the upper and lower jaws was greater in females (P < or = 0.01). Linear measurements were usually larger for males. The lips were less protrusive in males (P < or = 0.01), but the thickness was greater compared with females (P < or = 0.001). The nose was significantly more protrusive in males (P < or = 0.001). When the Icelandic sample was compared with closely related ethnic groups, such as the Swedes and the Danes, it was interesting to note that the Icelanders seem to be more like the Swedes than the Danes.

Adult↗