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PubMed1990

Tenascin distribution in the normal human breast is altered during the menstrual cycle and in carcinoma.

Tenascin is a novel extracellular matrix glycoprotein which appears to have a major role in tissue development. Previous studies have stated that tenascin is absent from the normal human, rat and mouse breast, its distribution being restricted to embryonic and malignant mammary tissues. No previous studies have investigated tenascin distribution as a function of the normal menstrual cycle. Therefore this study addresses the cyclical appearance of tenascin in the normal breast and associated changes in distribution in preinvasive cancer (carcinoma-in-situ) and invasive infiltrating ductal carcinoma. Tenascin is present in the normal human adult mammary gland, principally in the basement membrane, sub-basement-membrane zone and delimiting layer of fibroblasts around the ductules. Both the distribution and quantity of tenascin change during the menstrual cycle. In carcinoma-in-situ (preinvasive cancer) tenascin is present in the attenuated basement membrane/sub-basement-membrane zone around the expanded ductules and in small amounts in the stroma. In infiltrating ductal carcinoma, tenascin is absent from the remnants of the basement membrane and sub-basement-membrane zone but greatly increased in the adjacent intralobular and interlobular stroma. Therefore, if tenascin is used as a basement membrane/sub-basement-membrane marker for distinguishing carcinoma-in-situ from invasive ductal carcinoma, the time of the menstrual cycle is of importance in interpreting the biopsy appearance. This study suggests that the optimal time for biopsy is between weeks 3 and 4 of the cycle, to avoid confusion between the normal low levels of tenascin (due to hormonal status) and those due to microinvasive disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1987

PFK inhibition test for cancer detection: clinical applications and mechanisms of PFK inhibition.

A newly established cancer marker, the PFK inhibition test, has been further examined for its capacity to detect malignant neoplasms irrespective of the organs in which cancer cells start proliferating. We tested 1,160 sera from cancer patients and compared them with 756 normal sera, using histograms and normal paper for analysis of accumulated frequency. PFK activity through the influence of normal sera showed normal distribution, and cancerous sera shifted to the inhibitory site with an irregular shape. From these analyses, the patients were classified into the following types: normal range: PFK greater than SD (standard deviation of PFK activity in normal sera); suspicious range: SD greater than PFK greater than 2SD, must be given the PFK test again; and dangerous range: PFK less than 2SD, further examination must be carried out to detect cancer. Fifty percent of the sera from all the cancer patients inhibited PFK beyond 2 SD of normal sera. We also analyzed organ-associated PFK distribution, eg, gastric, colorectal, and mammary cancer. In gastric cancer, PFK inhibition was stronger in accordance with how far a particular stage of cancer had progressed. However, 50% of sera from stage I gastric cancer patients was positive beyond the cut-off line of 2 SD. We examined 104 sera from patients diagnosed as benign prostatic hypertrophy and found malignant cells in 10 patients whose sera tended to be positive in PFK inhibition. The PFK inhibitory factor in the body fluids of cancer patients was fractionated by Sephadex G-75 gel filtration and DEAE ion exchange chromatography. The approximate molecular weight of this factor was 13,000 daltons. The factor was resistant to heat and acid (0.1 N HCl and H2SO4) and was sensitive to 0.1 N NaOH and phosphate buffer. Diluted sulfuric acid and ammonium sulfate made an inactive NaOH-treated sample active when lyophilized following dialysis against distilled water. PFK inhibition by cancerous sera was eliminated by fructose-2,6-bisphosphate (the strongest activator of PFK) in a dose-dependent manner. PFK attached to agarose beads was found to be reversible even after being inhibited by cancerous body fluids and ATP water solution. Although PFK is apt to decay in a low pH range, the established procedure did not destroy PFK, but induced a direct inhibition of PFK by ATP through the ATP inhibition site on the PFK molecule. The PFK inhibitor may possibly function as a proton carrier and release protons to activate the ATP inhibition site.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

PubMed1985

A general noninteractive multiple toxicity model including probit, logit, and Weibull transformations.

A multiple toxicity model for the quantal response of organisms is constructed based on an existing bivariate theory. The main assumption is that the tolerances follow a multivariate normal distribution function. However, any monotone tolerance distribution can be applied by mapping the integration region in the n-dimensional space of transforms on the n-dimensional space of normal equivalent deviates. General requirements to noninteractive bivariate tolerance distributions are discussed, and it is shown that bivariate logit and Weibull distributions, constructed according to the mapping procedure, meet these criteria. The univariate Weibull dose-response model is given a novel interpretation in terms of reactions between toxicant molecules and a hypothetical key receptor of the organism. The application of the multiple toxicity model is demonstrated using literature data for the action of gamma-benzene hexachloride and pyrethrins on flour beetles (Tribolium castaneum). Nonnormal tolerance distributions are needed when the mortality data include extreme response probabilities.

Analysis of Variance↗

PubMed1999

Development of interstitial cells of Cajal and pacemaking in mice lacking enteric nerves.

BACKGROUND & AIMS: Development of interstitial cells of Cajal (ICC) requires signaling via Kit receptors. Kit is activated by stem cell factor (SCF), but the source of SCF in the bowel wall is unclear and controversy exists about whether enteric neurons express the SCF required for ICC development. METHODS: Glial cell line-derived neurotrophic factor (GDNF) knockout mice, which lack enteric neurons throughout most of the gut, were used to determine whether neurons are necessary for ICC development. ICC distributions were determined with Kit immunofluorescence, and function of ICC was determined by intracellular electrical recording. RESULTS: ICC were normally distributed throughout the gastrointestinal tracts of GDNF-/- mice. Intracellular recordings from aganglionic gastrointestinal muscles showed normal slow wave activity at birth in the stomach and small intestine. Slow waves developed normally in aganglionic segments of small bowel placed into organ culture at birth. Quantitative polymerase chain reaction showed similar expression of SCF in the muscles of animals with and without enteric neurons. Expression of SCF was demonstrated in isolated intestinal smooth muscle cells. CONCLUSIONS: These data suggest that enteric neurons are not required for the development of functional ICC. The circular smooth muscle layer, which develops before ICC, may be the source of SCF required for ICC development.

Animals↗

PubMed1997

Quantitative and qualitative immunohistochemistry of T cell subsets and MHC class II expression in the canine small intestine.

In man and rodents, cells of the gastrointestinal immune system include B and T lymphocytes, granulocytes, macrophages and dendritic cells. Abnormalities in leucocyte numbers and function have been described in diseases of humans, such as coeliac disease and inflammatory bowel disease. The purpose of this study is to describe the normal distribution of T cells and MHC Class II expression in the small intestine of clinically normal dogs, to allow subsequent comparison with disease states. Full-thickness sections of duodenum, jejunum and ileum from seven young adult beagle dogs were immediately snap-frozen following euthanasia. Avidin-biotin-enhanced immunocytochemistry was used to detect expression of canine CD3, CD4, CD8 and MHC Class II antigens. Positively stained lamina propria cells were quantified using an eyepiece graticule, and positively stained intraepithelial cells by counts per 100 epithelial cells. In the lamina propria, the density of all leucocyte subsets was significantly increased towards the villus tip for all regions (p < 0.05). There was no apparent difference in the distribution of CD3+, CD4+ and CD8+ leucocytes between the three portions of the small intestine. The ratios of CD4+ cells to CD8+ cells in the lamina propria and epithelium were 59:41 and 15:85, respectively. Subtractive analysis suggested that 50-55% of CD3+ intraepithelial cells were CD4-CD8-. MHC Class II expression was apparent upon lamina propria cells with a dendritic morphology, as well as round cells. Epithelial MHC Class II expression was apparent in 7/7 ileal sections, compared with only 1/7 duodenal and 1/7 jejunal sections. This study shows that the small intestinal mucosa of the dog contains similar leucocyte populations to those found in other species, and suggests that these cells may play similar roles in gastrointestinal immunity.

Animals↗

PubMed2004

Decreased interstitial cells of Cajal in the sigmoid colon of patients with slow transit constipation.

BACKGROUND AND AIMS: Slow transit constipation (STC) is a colonic motor disorder that is characterized by measurably delayed movement of materials through the colon. Although abnormalities in the neuronal networks of the colon have been demonstrated in patients with STC, the etiology of STC remains unclear. Interstitial cells of Cajal (ICC) have been shown to be the pacemaker cells of the intestine and have been implied in the pathogenesis of a number of gastrointestinal motility dysfunctions, including idiopathic STC. This study aimed to determine the normal distribution of ICC within the colon of the Chinese and also to determine if ICC are decreased in Chinese STC patients. PATIENTS AND METHODS: Twelve patients with STC and eight age-matched normal controls were studied. Specimens of sigmoid colon were obtained immediately after resection. ICC were identified with a monoclonal antibody to c-kit by an indirect immunofluorescence method. Immunostained tissues were examined with a laser scanning confocal microscope and the area occupied by ICC was calculated with an image analysis system. RESULTS: ICC were located in the external muscle layers including myenteric plexus (MP) and submucosal border (SMB). Two types of Kit-positive ICC were observed: bipolar cells characterized by one or two long processes and multipolar cells characterized by long stellate processes extending in various directions. A higher percentage of ICC was present in the MP regions and circular muscle (CM) layers compared with the SMB and longitudinal muscle (LM) layers. Tissues from STC patients showed a considerable decrease in the number of ICC located in the four regions (ICC-LM, ICC-MP, ICC-CM, ICC-SMB), especially the ICC-SMB, in which ICC almost completely disappeared. CONCLUSIONS: Similar distribution of ICC was observed in the normal sigmoid colon of the Chinese. Decreased area of c-kit+ ICC may play an important role in the pathophysiology of STC. It remains to be determined whether the loss of ICC is primary or secondary to another lesion.

Adult↗

PubMed2006

Ramsay-curve item response theory (RC-IRT) to detect and correct for nonnormal latent variables.

Popular methods for fitting unidimensional item response theory (IRT) models to data assume that the latent variable is normally distributed in the population of respondents, but this can be unreasonable for some variables. Ramsay-curve IRT (RC-IRT) was developed to detect and correct for this nonnormality. The primary aims of this article are to introduce RC-IRT less technically than it has been described elsewhere; to evaluate RC-IRT for ordinal data via simulation, including new approaches for model selection; and to illustrate RC-IRT with empirical examples. The empirical examples demonstrate the utility of RC-IRT for real data, and the simulation study indicates that when the latent distribution is skewed, RC-IRT results can be more accurate than those based on the normal model. Along with a plot of candidate curves, the Hannan-Quinn criterion is recommended for model selection.

Area Under Curve↗

PubMed1998

Expression of ras, c-myc, and p53 proteins in cervical intraepithelial neoplasia.

BACKGROUND: The development of cervical carcinoma is influenced by multiple factors, including the presence of certain high risk types of human papillomavirus. The purpose of the current study was to investigate possible cooperating genetic changes by examining the expression of p53, p62 myc, and p21 ras in cervical biopsy specimens. METHODS: Three hundred and ninety-five cervical biopsy specimens representing normal through high grade cervical intraepithelial neoplasia (CIN) were screened by immunohistochemistry for expression of p53, p62myc, and p21ras. RESULTS: Neither the proportion of tissues staining positive for a given protein nor the staining patterns within the epithelial layers differed significantly among normal or CIN biopsy samples. However, grade specific nuclear staining of p21ras was found in the cells of 10 lesions that were classified as CIN I by histology. CONCLUSIONS: These results established the normal distribution and expression patterns of p53, p62myc, and p21ras within 395 cervical biopsy samples representing normal through CIN III histology. The expression of these proteins (e.g., staining intensity and layer of epithelium staining positive) is similar in normal tissues and those demonstrating all grades of CIN.

Carcinoma in Situ↗

PubMed2002

Ginkgo biloba for cognitive impairment and dementia.

BACKGROUND: Extracts of the leaves of the maidenhair tree, Ginkgo biloba, have long been used in China as a traditional medicine for various disorders of health. A standardized extract is widely prescribed in Germany and France for the treatment of a range of conditions including memory and concentration problems, confusion, depression, anxiety, dizziness, tinnitus and headache. The mechanisms of action are thought to reflect the action of several components of the extract and include increasing blood supply by dilating blood vessels, reducing blood viscosity, modification of neurotransmitter systems, and reducing the density of oxygen free radicals. OBJECTIVES: The aim of the review is to assess the efficacy and safety of Ginkgo biloba for the treatment of patients with dementia or cognitive decline. SEARCH STRATEGY: Trials were identified on 26 June 2002 through a search of the CDCIG Specialized Register which contains records from all main medical databases (MEDLINE, EMBASE, CINAHL, PsycINFO, SIGLE,LILACS), from ongoing trials databases such as Clinicaltrials.gov and Current Controlled Trials and many other sources. The search terms used were ginkgo*, tanakan, EGB-761, EGB761 and "EGB 761". SELECTION CRITERIA: All relevant, unconfounded, randomized, double-blind controlled studies, in which extracts of Ginkgo biloba at any strength and over any period were compared with placebo for their effects on people with acquired cognitive impairment, including dementia, of any degree of severity. DATA COLLECTION AND ANALYSIS: Data for the meta-analyses are based on reported summary statistics for each study. For the intention-to-treat analyses we sought data for each outcome measure on every patient randomized, irrespective of compliance. For the analyses of completers we sought data on every patient who completed the study on treatment. For continuous or ordinal variables, such as psychometric test scores, clinical global impression scales, and quality of life scales, there are two possible approaches. If ordinal scale data appear to be approximately normally distributed, or if the analyses reported by the investigators suggest that parametric methods and a normal approximation are appropriate, then the outcome measures will be treated as continuous variables. The second approach, which may not exclude the first, is to concatenate the data into two categories which best represent the contrasting states of interest, and to treat the outcome measure as binary. For binary outcomes, the endpoint itself is of interest and the Peto method of the typical odds ratio is used. MAIN RESULTS: Overall, there are no significant differences between Ginkgo and placebo in the proportion of participants experiencing adverse events. Most studies report the analyses of data from participants who completed the treatment, there are few attempts at ITT analyses. Therefore we report completers analyses only. The CGI scale, measuring clinical global improvement as assessed by the physician, was dichotomized between participants who showed improvement and those who were unchanged or worse. There are benefits associated with Ginkgo (dose less than 200mg/day) compared with placebo at less than 12 weeks (54/63 showed improvement compared with 20/63, OR 15.32, 95% CI 5.90 to 39.80, P=<.0001), and Ginkgo (dose greater than 200mg/day) at 24 weeks (57/79 compared with 42/77, OR 2.16, 95% CI 1.11 to 4.20, P=.02). Cognition shows benefit for Ginkgo (dose less than 200mg/day) compared with placebo at 12 weeks (SMD -0.57, 95% CI -1.09, -0.05, P=0.03, random effects model), Ginkgo (greater than 200 mg/day) at 12 weeks (SMD -0.56, 95% CI -1.12 to -0.0, P=0.05), at 12 weeks (Ginkgo any dose) (SMD -0.71, 95% CI -1.23 to -0.19 P=0.008, random effects model) at 24 weeks (Ginkgo any dose) (SMD -0.17, 95% CI -0.32 to -0.02 P=0.03) and at 52 weeks (Ginkgo less than 200 mg/day) (SMD -0.41, 95% CI -0.71 to -0.11, P=<.01). Activities of Daily Living (ADL) shows benefit for Ginkgo (dose less than 200mg/day) compared with placebo at 12 weeks (SMD -1.10, 95% CI -1.79, -0.41, P=0mg/day) compared with placebo at 12 weeks (SMD -1.10, 95% CI -1.79, -0.41, P=<.01), Ginkgo (dose less than 200 mg/day ) at 24 weeks (SMD -0.25, 95% CI -0.49 to -0.00, P=.05), and at 52 weeks (Ginkgo less than 200 mg/day) (SMD -0.41, 95% CI -0.71 to -0.11, P=<.01). Measures of mood and emotional function show benefit for Ginkgo (dose less than 200 mg/day) compared with placebo at less than 12 weeks (SMD -0.51, 95% CI -0.99 to -0.03, P=.04) and Ginkgo (dose less than 200mg/day) at 12 weeks (SMD -1.94, 95% CIs -2.73, -1.15 P=<.0001). There are no significant differences between Ginkgo and placebo in the proportion of participants experiencing adverse events. There are no data available on Quality of Life, measures of depression or dependency. REVIEWER'S CONCLUSIONS: Ginkgo biloba appears to be safe in use with no excess side effects compared with placebo. Many of the early trials used unsatisfactory methods, were small, and we cannot exclude publication bias. Overall there is promising evidence of improvement in cognition and function associated with Ginkgo. However, the three more modern trials show inconsistent results. Our view is that there is need for a large trial using modern methodology and permitting an intention-to-treat analysis to provide robust estimates of the size and mechanism of any treatment effects.

Cognition Disorders↗

PubMed2004

The MTT assays of bovine retinal pericytes and human microvascular endothelial cells on DLC and Si-DLC-coated TCPS.

MTT (Tetrazolium)-assay suggests that diamond-like carbon (DLC) and silicon-doped DLC (Si-DLC) films obtained under appropriate deposition parameters are not toxic to bovine retinal pericytes, and human microvascular endothelial cells (HMEC). The observed frequency distributions of the optical density (OD) values indicative of cell viability are near Gaussian-normal distribution. One-way ANOVA indicates that at 0.05 levels the population means are not significantly different for the coated and control samples. The observed OD values depend on the cell line (cell growth/metabolic rate), possibly cell cycle stage, the deposition parameters-bias voltage, ion energy, pressure, argon precleaning, and the dopant. For colored thin films like DLC with room temperature photoconductivity and photoelectric effects, it is important to account for the OD contribution from the coating itself. MTT assay, not surprisingly, seems not to be highly sensitive to interfacial cellular interaction resulting from the change in the film's nanostructure, because the tetrazolium metabolism is mainly intracellular and not interfacial. The thin films were synthesized by 13.56 MHz RF-PECVD using argon and acetylene as source gases, with tetramethylsilane (TMS) vapor introduced for silicon doping. This study could be relevant to biomedical application of the films in the eye, peri-vascular, vascular compartments, and for cell-tissue engineering.

Animals↗

PubMed2006

Addressing the issues that arise in analysing multicentre cost data, with application to a multinational study.

Differences in the mean, spread and skewness of cost data collected from different countries present problems for analysis and interpretation. Here we develop generalised linear multilevel models to estimate the effects of patient and national characteristics on costs. Using gamma distributions and multiplicative effects for patient characteristics fitted the data better than models which assumed normal distributions or estimated additive effects. A multilevel gamma model is employed to allow for heterogeneity in the effects of patient case-mix across centres. Analysis of multinational cost data must recognise differences in mean, spread and skewness across centres, as well as the data's hierarchical structure.

Costs and Cost Analysis↗

PubMed1999

Gonadal function in young women with Down syndrome.

OBJECTIVE: Investigations suggest an increased incidence of gonadal dysfunction in patients with Down syndrome. New features, Alzheimer disease and osteoporosis emerge in these individuals. Therefore, hormonal investigation in persons with Down syndrome is pursued. METHODS: Thirteen females with trisomy 21 (23.65 +/- 3.23 years old) participated in the study. Ultrasound studies were performed to explore the internal genitals. Blood samples were taken for the determination of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin (PRL), dehydroepiandrosterone sulfate (DHEA-S), testosterone (T) and 17-hydroxyprogesterone (17-OHP). RESULTS: The patients were at stage V of sexual development. Ultrasonography demonstrated normal uterine and ovarian size and endometrial thickness as well. The ovaries of all patients contained follicles of normal distribution and various sizes. The mean concentrations of FSH, DHEA-S and E2 were normal. The level of PRL was significantly higher than that of the controls, but within the normal lab range. The levels of LH, T and 17-OHP were significantly elevated, compared to those of the control group (P < 0.05, P < 0.01, P < 0.001, respectively). CONCLUSIONS: Our data produce new information on the gonadal function of Down syndrome women. Specific studies on pituitary-gonadal and pituitary-adrenal axis function are needed.

Adult↗

PubMed1976

Mucosal recovery in treated childhood celiac disease (gluten-sensitive enteropathy).

Follow-up studies on 36 children, in whom celiac disease (gluten-sensitive enteropathy) was established by gluten challenge, were carried out after management on gluten-free diets for a mean of six years. Evaluations included measurement of height and weight, which for the group approximated normal distributions, and histologic examination of the duodenal or jejunal mucosa. Mucosal morphology was regarded as normal in 16, and there were minimal changes in 20. Epithelial cell height was within the normal range in all the children. Interepithelial lymphocytes were within normal range in the majority and lymphoid cells in the lamina propria were not different from those in control subjects. Mucosal lactase was significantly lower in patients than in control subjects in the duodenum and the jejunum, whereas sucrase and alkaline phosphatase values were significantly lower in the jejunum but not in the duodenum. Low content of mucosal lactase and increased numbers of interepithelial lymphocytes may be sensitive indicators of persisting ingestion of gluten in mucosa that is otherwise normal or approximately so in appearance.

Adolescent↗

PubMedDate not supplied

A database for environmental contaminants in traditional foods in northern and Arctic Canada: development and applications.

The potential health effects of environmental contaminants in traditional food has become a concern among northern communities because of the presence of environmental contaminants in the Arctic ecosystem. Exposure assessments are needed but they require comprehensive dietary information and contaminant data. Over the last 10 years, there has been considerable effort to monitor the level of contaminants in fish and wildlife collected from different regions in northern and Arctic Canada. The development of a database and its application for dietary contaminant exposure assessment are described. We conducted an extensive literature review on levels of environmental contaminants in northern and Arctic Canada. The ranges of levels of four contaminants of major concern (chlordane, mercury, polychlorinated biphenyls and toxaphene) in 81 species of marine mammals, terrestrial mammals, birds, fish and plants are summarized. These data represent 69% of the 117 species of fish, wildlife and plants mentioned in our dietary interviews conducted in the northern communities. A significant percentage of the foods had contaminant levels exceeding the guidelines used by Health Canada for market food consumed by the 'southern' populations. Mathematic modelling of the distributions of the data showed that contaminant levels in most food groups are log-normally distributed and have a typical coefficient of variation of about 100%. Examples are presented to demonstrate the use of the data for contaminant exposure assessment. Average contaminant exposure levels estimated using the database for two communities are comparable to those obtained previously using community specific data. With the current knowledge of environmental contaminant levels in the northern traditional food system, it may be feasible to conduct preliminary risk assessment of dietary exposure of environmental contaminants when some diet information for a community is available. Further sampling and analysis may be needed only for confirmation purposes.

Animals↗

PubMed1977

National study of health and growth: standards of attained height, weight and triceps skinfold in English children 5 to 11 years old.

The National Study of Health and Growth (NSHG) was set up in 1972 to monitor growth in primary schoolchildren. Each year 8000 children in England (most parts except the south-east) and 2500 in Scotland are measured. Data from the first year have been used to obtain standards of height, weight and triceps skinfold for ages 5 to 11 inclusive, and ellipse contours of weight by height for each year of age. The distributions of weight and triceps skin fold were positively skew; logarithmic transformations led to satisfactory Normalized distributions. Centiles within each age group, calculated from the mean and standard deviation of the transformed variables, were closely similar to the observed centiles. Scottish children were lighter and shorter than English children in all age-sex groups. The heights and weights of English children in the NSHG were very similar to those published by Tanner, Whitehouse and Takaishi (1966). Triceps skinfold agreed closely with the data of Tanner and Whitehouse (1975) for the 50th and 97th centiles in boys, but our 3rd centile was well above its counterpart. Girls had higher skinfolds than girls in Tanner's data at the 3rd and 50th centiles. The triceps skinfolds of Scottish children were lower than those of English children throughout the age range and for all the centiles in both sexes. An example is given of the use of our ellipse contours of height and weight for surveillance of a population of children. Children's height is discussed in relation to variability over time and between different parts of the country.

Arm↗

PubMed2002

Early faecal excretion of inhaled plutonium.

Special individual monitoring has been performed for suspected cases of inhalation of plutonium at the Tokai Works of the Japan Nuclear Cycle Development Institute (JNC). Some experimental data obtained from this special individual monitoring during the past 20 years are presented and discussed in this paper. Our experience suggests the following conclusions. The daily plutonium excretion rate, normalised to the total excretion for the first 5 days after inhalation, was approximately in agreement with the latest ICRP 78 dosimetric model. Maximum faccal excretion is observed on the second day after inhalation of plutonium compounds. On the other hand, the activity ratio for total alpha activity observed in early faeces to that detected in nasal swabs showed a wide distribution range, and it was proven that variations in this ratio followed a log-normal distribution. The logarithmic mean probability is about 2.1 for PuO2 and about 15.7 for Pu(NO3)4. In practice, a conservative dose assessment from nasal swabs can be performed on the basis of these experimental ratios.

Feces↗

PubMed1988

Comparison of three lithium dosing methods in 950 "subjects" by computer simulation.

This study compared the accuracy of the one-point method (OPM) of Cooper et al., the repeated one-point method (ROPM) using a 12 h initial dosage interval (ROPM-12), and the ROPM using a 24 h initial dosage interval (ROPM-24) for predicting lithium steady-state concentrations after lithium carbonate 600 mg every 12 h. Pharmacokinetic values for elimination rate constant (k), volume of distribution (V), and absorption rate constant (ka) were generated randomly for 950 subjects to produce normally distributed values of the parameters with target means and standard deviations in accordance with values reported in the literature. Errors with a mean of zero and a standard deviation of +/- 5% (SD5%) and +/- 10% (SD10%) were added to the calculated lithium concentrations used in the prediction methods to simulate assay and timing errors. The mean (+/- SD) values generated for k, ka, and V were 0.035 +/- 0.008 (h-1), 0.897 +/- 0.059 (h-1), and 40.97 +/- 5.27 (L), respectively. Prediction errors were smallest with the OPM (SD5%, SD10%) and ROPM-24 (SD5%). There was a significant correlation between k and the prediction error for the OPM (SD5%, SD10%) and the ROPM-24 (SD5%). The OPM was the most accurate of the methods studied; however, it tended to underpredict actual concentrations in subjects with long half-lives.

Computer Simulation↗

PubMed1994

Gliding-window fast Fourier transform analysis of the entire QRS complex and the distribution of area ratio peaks in healthy subjects and patients with myocardial infarction.

BACKGROUND: The high-frequency contribution (i.e. 60-120 Hz) within the QRS complex of the surface ECG is supposed to be related to the arrhythmogenic substrate underlying sustained ventricular tachycardia in patients with coronary artery disease. One of the factors that prevents a wider clinical application of spectral analysis based on the fast Fourier transform is the considerable intra-individual variability of its results. This study presents a novel alternative approach of frequency-domain analysis, aimed at minimizing this methodological drawback. METHODS: The proposed method uses gliding-window fast Fourier transform analysis of the signal-averaged ECG to provide values expressing the area ratio for two predefined frequency ranges (60-120 Hz divided by 0-120 Hz). The term gliding window is derived from the methodological principle by which the window analyzed is moved from the onset of the QRS complex into the ST segment. Values of area ratios obtained for every time instant of the interval of gliding are the basis for construction of curves. These are further analyzed in order to find patterns that characterize abnormal ventricular activation, with special emphasis on the identification of arrhythmogenic correlates. RESULTS: In a group of 30 healthy subjects, the distribution of area ratio peaks was characterized according to their value and timing. The distribution of area ratio peaks in 43 patients with myocardial infarction differed substantially from the normal distribution in the control group. The amplitude of the peaks and their timing was not related to the occurrence of late ventricular potentials. CONCLUSION: The method of gliding-window fast Fourier transform analysis eliminates the variability of results obtained by traditional spectral analysis of the ECG signal. A higher number and a different distribution of high-frequency peaks during the QRS complex in postmyocardial infarction patients reflect abnormal ventricular activation. However, late ventricular potentials are not related to a higher proportion of high frequencies in the corresponding time interval within the terminal QRS complex.

Adult↗

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