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PubMed1999

Biomechanical effects of intraspecimen variations in trabecular architecture: a three-dimensional finite element study.

Trabecular architecture is considered important in osteoporosis and has been quantified by a variety of mean parameters characteristic of a whole specimen. Variations within a specimen, however, have been mostly ignored. In this study, the theoretical effects of these intraspecimen variations in architecture on predicted mechanical properties were investigated through a three-dimensional finite element parameter study that simulated variations in trabecular thickness in a controlled manner. An irregularly spaced lattice of different sized rods was used to simulate trabecular bone in three distinct volume fraction ranges, representing young, middle-aged, and elderly vertebral bone. Beta distributions (a type of non-normal distribution) of trabecular thickness with coefficients of variation of either 25%, 40%, or 55% were applied to the rods in each model, and 225 simulations of uniaxial compression tests were performed to obtain modulus values. Percent modulus reductions of 22% and 43% were predicted when the intraspecimen coefficient of variation in trabecular thickness was increased from 25% to 40% and from 25% to 55%, respectively, for models of equal volume fraction. Furthermore, this trend was predicted to be independent of volume fraction. We conclude, therefore, that consideration of the intraspecimen trabecular thickness variation in conjunction with volume fraction may improve the ability to predict trabecular modulus compared with use of volume fraction alone. Further, the model suggests that if age, disease, or drug treatments increase trabecular thickness variation, this may be detrimental to mechanical properties.

Adult↗
PubMed1979

Glucose tolerance and erythrocyte insulin receptors in Friedreich's ataxia.

Detailed in vivo and in vitro studies of glucose and insulin metabolism in Friedreich's ataxia patients and unaffected family members have further defined the extent of the abnormalities in carbohydrate metabolism. The high incidence of glucose intolerance and a hyperinsulinemic response to a glucose challenge in a high percentage of Friedreich's ataxia patients has been confirmed. An increased incidence of glucose intolerance among heterozygotes is suggested, while the siblings show a more normal distribution of diabetes and a nearly normal insulin response to the glucose tolerance test. Human growth hormone patterns are normal for all groups. Preliminary studies of insulin binding to erythrocytes suggest a difference in the binding characteristics among diabetic Friedreich's ataxia patients, while the binding in the non-diabetic Friedreich's ataxia group is similar to that of non-diabetic controls. Results from a small group of non-diabetic siblings suggest a normal insulin binding, while a tendency toward increased binding at low insulin concentrations among diabetic family members is noted.

Diabetes Complications↗
PubMed2003

Correlation of Ki-67, p53, and Adnab-9 immunohistochemical staining and ploidy with clinical and histopathologic features of severely dysplastic colorectal adenomas.

Variations of Ki-67, p53, and Adnab-9 monoclonal antibody reactions in colonic adenomas may be associated with colonic cancer risk. We studied the predictive value of these markers for adverse behavior in severely dysplastic colorectal adenomas, such as an associated carcinoma, multiplicity of adenomas, and subsequent development of adenomas. For this purpose we compared theclinical, gross, and histologic characteristics of highly dysplastic index polyps in 42 patients with Ki 67, p53, and Adnab-9 immunostaining and other molecular markers. Polyps were removed endoscopically, and severely dysplastic polyps were stained immunohistochemically with Ki-67, Adnab-9, and p53 protein by the avidin biotin conjugate (ABC) technique. Quantitative DNA (QDNA) was analyzed by computer-assisted image analysis. Ki-67 immunohistochemistry showed reversal of normal distribution of nuclear staining from the normal basal position to the upper third of the colonic crypts. This abnormality of immunostaining in dysplastic adenomas was the earliest detected by the panel we used. A statistically significant correlation was seen between invasiveness of carcinoma in the index polyp and polyp size (P = 0.003), sessile morphology (P = 0.037), and villous or tubulovillous histology (P = 0.019). In the index adenoma, p53 positivity was correlated with multiplicity at initial examination (P = 0.053), villous histology (P = 0.053), invasiveness of carcinoma (P < 0.003), and recurrence of colorectal adenomas (P = 0.025). Although p53 positivity and aneuploidy were correlated with invasiveness of carcinoma in the index polyp (P = 0.025), Adnab-9 positivity was not. However, Adnab-9 positivity in the index polyp was associated with multiplicity of adenomas (P = 0.04) as well as recurrence of adenomas (P < 0.024). In conclusion, in addition to the morphologic and histologic markers already known, Ki-67, Adnab-9 antibody, and p53 protein may be prognostic indicators useful in follow-up of patients with severely dysplastic colorectal adenomas. Adnab-9 antibody may identify a field defect in above-average-risk adenoma-bearing patients.

Adenomatous Polyps↗
PubMed2006

Design of a sampling plan to detect ochratoxin A in green coffee.

The establishment of maximum limits for ochratoxin A (OTA) in coffee by importing countries requires that coffee-producing countries develop scientifically based sampling plans to assess OTA contents in lots of green coffee before coffee enters the market thus reducing consumer exposure to OTA, minimizing the number of lots rejected, and reducing financial loss for producing countries. A study was carried out to design an official sampling plan to determine OTA in green coffee produced in Brazil. Twenty-five lots of green coffee (type 7 - approximately 160 defects) were sampled according to an experimental protocol where 16 test samples were taken from each lot (total of 16 kg) resulting in a total of 800 OTA analyses. The total, sampling, sample preparation, and analytical variances were 10.75 (CV = 65.6%), 7.80 (CV = 55.8%), 2.84 (CV = 33.7%), and 0.11 (CV = 6.6%), respectively, assuming a regulatory limit of 5 microg kg(-1) OTA and using a 1 kg sample, Romer RAS mill, 25 g sub-samples, and high performance liquid chromatography. The observed OTA distribution among the 16 OTA sample results was compared to several theoretical distributions. The 2 parameter-log normal distribution was selected to model OTA test results for green coffee as it gave the best fit across all 25 lot distributions. Specific computer software was developed using the variance and distribution information to predict the probability of accepting or rejecting coffee lots at specific OTA concentrations. The acceptation probability was used to compute an operating characteristic (OC) curve specific to a sampling plan design. The OC curve was used to predict the rejection of good lots (sellers' or exporters' risk) and the acceptance of bad lots (buyers' or importers' risk).

Coffee↗
PubMed1962

Study of mitochondria in rat liver. Quantitative electron microscopy.

The electron microscope has been used to determine the weight distribution of isolated subcellular particles from normal rat liver. The following results are reported: (1) There exist at least two well defined weight populations of subcellular particles; their respective median weights are 1.3 x 10(-14) and 11 x 10(-14) gm. The lighter fraction is considered to consist of lysosomes, the heavier of mitochondria. (2) The mitochondrial fraction shows a log-normal distribution of the particle weight. (3) By the introduction of morphologic criteria, the mitochondrial fraction is divided into two groups, one consisting of a spherical, the other of an oblong type of particle. The data found support the following concepts: (a) Mitochondria increase their weight from a certain size up by linear growth. (b) Mitochondria divide. The division is not necessarily symmetric; in all cases, however, one part of the division product is a spherical particle. It is felt that these results constitute a valuable demonstration of the general capabilities of quantitative electron microscopy and may stimulate many other useful applications of this technique in cytology, bacteriology, and virology.

Animals↗
PubMed2006

Inhaled azithromycin therapy.

The treatment of pulmonary infectious diseases with pharmaceutical aerosols is an attractive option considering the accessibility of the lungs for topical drug delivery. Aerosols have been targeted to the lungs for the treatment of asthma with great success. Current therapies for other diseases, including Pseudomonas aeruginosa, Pneumocystis jirovecii (formerly Pneumocystis carinii), and mycobacterial infections, remain suboptimal due to the efficacy/safety profile. This may be improved by aerosol targeted pulmonary drug delivery. Azithromycin is a broad spectrum antibiotic that acts by inhibiting protein synthesis. It is associated with side effects that might be avoided by aerosol delivery to the lungs. In the present study three concentrations of azithromycin (10, 50, and 100 mg/mL) were delivered from three nebulizers (Acorn II, Updraft, and LC Plus) operated at 8 L/min. Particles size analyses were conducted by inertial impaction and laser diffraction. In addition, emitted doses were determined. A linear proportionality existed across the concentration range between nominal dose and both fine particle dose/fraction and emitted dose, with R2 > 0.999 in all cases. The mass median aerodynamic diameter increased from 1.4 to 1.9 microm between 10 and 100 mg/mL of azithromycin solution concentration for the Acorn II. The particle size distributions were not all log-normally distributed. The median particle size delivered from the devices was largest for the Updraft (2.8 microm) and smallest for the Acorn II (1.9 microm) for 100 mg/mL azithromycin solution concentrations. The efficiencies of small particle delivery (%<4.7 microm) were as follows, LC Plus = Acorn II (85%) > UpDraft (75%). However, the emitted dose from the LC Plus (55 mg/min) was higher than the Acorn II (31 mg/min) to maximize lung exposure to the aerosol, small median diameters and broad particle size distributions would be most effective. This study demonstrates that the dose delivered to the lungs will be maximized, under the current operating conditions by adopting the LC Plus, and high (100 mg/mL) azithromycin concentrations.

Administration, Inhalation↗
PubMed1982

Total glycosylated haemoglobin (HbA1) levels in diabetic children.

Total glycosylated haemoglobin (HbA1) levels from capillary blood were studied retrospectively during a 1-year period in 148 diabetic children aged between 1.9 and 16.8 years. The clinic range for HbA1 was 6.7 to 22.2% and the results were normally distributed (mean +/- SD 13.2 +/- 2.8%). The normal range in non-diabetics using this method is 4.9 to 8.0%. Results from children who had had diabetes for more than 5 years were higher than those from children with diabetes of 2 to 5 years' duration. Girls had higher average values during the 1-year period than boys. HbA1 measurement serves to identify the deficiencies of current diabetic treatment regimens. It also has more immediate practical benefits in focusing attention on children whose control is deteriorating.

Adolescent↗
PubMed1978

Distribution of pulmonary responsiveness to aerosol histamine in dogs.

Dose-response curves to aerosol histamine in 102 anesthetized, intubated, spontaneously breathing dogs revealed a spectrum of airway responsiveness with a greater than 40-fold difference between the most and the least sensitive animals. The frequency distribution of responses fits a log normal distribution. No correlation was found between sex, age, or control values of dynamic compliance (Cdyn) and lung resistance (RL) and the dose of histamine required to cause a response. Repetitive studies in 17 dogs observed for up to 20 mo showed that the dose at which an individual dog would respond was reproducible within a narrow range and that the differences between dogs were highly significant (P greater than 0.001). The long-term reproducibility of the response to aerosol histamine in individual dogs suggests that short-term reversible airway insults are not responsible for the range in responses noted between animals.

Aerosols↗
PubMed2000

Characterization of obesity phenotypes in Psammomys obesus (Israeli sand rats).

Psammomys obesus (the Israeli sand rat) has been well studied as an animal model of Type 2 diabetes. However, obesity phenotypes in these animals have not been fully characterized. We analyzed phenotypic data including body weight, percentage body fat, blood glucose and plasma insulin concentration for over 600 animals from the Psammomys obesus colony at Deakin University to investigate the relationships between body fat, body weight and Type 2 diabetes using regression analysis and general linear modelling. The body weight distribution in Psammomys obesus approximates a normal distribution and closely resembles that observed in human populations. Animals above the 75th percentile for body weight had increased body fat content and a greater risk of developing diabetes. Increased visceral fat content was also associated with elevated blood glucose and plasma insulin concentrations in these animals. A familial effect was also demonstrated in Psammomys obesus, and accounted for 51% of the variation in body weight, and 23-26% of the variation in blood glucose and plasma insulin concentrations in these animals. Psammomys obesus represents an excellent animal model of obesity and Type 2 diabetes that exhibits a phenotypic pattern closely resembling that observed in human population studies. The obesity described in these animals was familial in nature and was significantly associated with Type 2 diabetes.

Adipose Tissue↗
PubMed1980

Extensive myocardial blood flow distribution through individual coronary artery bypass grafts.

The regional myocardial perfusion distribution of coronary artery bypass grafts were studied in 61 patients who received 162 grafts. Selective intragraft instillations of radioactive-labeled macroaggregated albumin particles were used to study perfusion. The extent of individual graft perfusion was assessed in 100 patent grafts. Regional myocardial blood flow distribution was similar to the blood flow distribution of the native vessel receiving the graft in 64 of 100 grafts and less than that expected of the native vessel in 12 grafts. However, 24 grafts demonstrated a blood flow distribution pattern which extended beyond the normal distribution expected of the native vessel receiving the graft. This extensive perfusion could be attributed to collateral vessels or retrograde flow. A high incidence of both graft and native vessel occlusion was found in areas receiving blood from these distant grafts with extensive distributions (16/24), and left ventricular wall motion was preserved or significantly improved postoperatively in 28/31 segments in such areas. When comparing angiographic and scintigraphic methods of evaluating myocardial perfusion, the angiogram underestimated the full extent of graft blood flow distribution in 13 of 24 instances (54 percent).

Coronary Angiography↗
PubMed1997

Estimated frequency of the RN- allele in Swedish Hampshire pigs and comparison of glycolytic potential, carcass composition, and technological meat quality among Swedish Hampshire, Landrace, and Yorkshire pigs.

The frequency of the dominant RN- allele (Rendement Napole) was estimated in purebred Swedish Hampshire pigs (n = 208) by using the estimated glycogen content in the longissimus muscle at slaughter (glycolytic potential; GP). Carriers (n = 177) and noncarriers (n = 31) of the RN- allele were compared with purebred Swedish Yorkshire (Y, n = 208) and Swedish Landrace (L, n = 114) pigs with respect to GP and carcass composition. Technological meat quality was compared between the RN phenotypes from the Hampshire breed and Yorkshire pigs. The distribution of GP deviated from a normal distribution in all three breeds. Hampshire pigs with GP > or = 183 micromol lactate equivalents per gram wet weight were regarded as carriers of the RN- allele (RN-/RN-, or RN-/rn+), and those constituted 85% of all Hampshire pigs evaluated, giving a frequency of .61 for the dominant allele (RN-). The RN- carriers had higher GP than noncarriers, Landrace, and Yorkshire pigs, but noncarriers and Landrace did not differ regarding GP. The two RN phenotypes did not differ in carcass composition, but the carriers were leaner than Landrace and Yorkshire, with larger proportions of meat plus bone in ham and back. Noncarriers and Yorkshire did not differ in leanness, but both these groups were leaner than Landrace. The RN- carriers had lower Napole yield (cured cooked muscle) and higher drip loss than noncarriers and Yorkshire, but in comparison with noncarriers they also had lower shear force values. In conclusion, the frequency of the RN- allele is high in purebred Swedish Hampshire. Most of the effects of the allele on technological meat quality (i.e., ultimate pH, water-holding capacity, and technological yield) found in crossbred pigs seem also to be consistent for purebred pigs. However, the RN- allele exerted less influence on meat content in purebred pigs.

Alleles↗
PubMed2003

The Li+/Na+ exchange in hypertension.

The red cell membrane Li+/Na+exchange is a heteroexchange that operates in either direction across the cell membrane. It binds either Li+ or Na+ on one side of the membrane and it exchanges the transported species for either Li+ or Na+ on the opposite side in a stoichiometric ratio of 1:1. In the population, Li+/Na+exchange is unimodally distributed but skewed to the right. Such distribution results from superimposition of two normal distributions. Many laboratories have shown that red-cell Li+/Na+ exchange is increased in patients with essential hypertension, compared with normotensive controls. Among the various alterations of cell membrane cation transport reported in hypertension, the increase of red-cell Li+/Na+ exchange has been most widely investigated and confirmed. Moreover, increased Li+/Na+ exchange has been found in some clinical conditions related to hypertension, such as overweight and diabetes. Among diabetic patients, Li+/Na+ exchange is particularly high in patients with nephropathy, hypertension, and microalbuminuria, leading to the hypothesis that it can be considered a cellular marker of the risk of developing diabetic nephropathy. Furthermore, it is associated with severe and drug-resistant hypertension, insulin resistance, vascular and cardiac hypertrophy, hyperlipidemia, obesity, family history of hypertension, and of major cardiovascular accidents suggesting that high Li+/Na+ exchange could be a biochemical marker for increased cardiovascular risk. Regardless of its the pathophysiological significance, its measurement could be of clinical use as an intermediate phenotype of increased cardiovascular risk.

Antiporters↗
PubMed2000

[Analyses of factors prolonging the length of hospital stay in elderly patients beginning hemodialysis].

The aim of the present study is to clarify the factors causing prolongation of the length of hospital stay in elderly patients beginning hemodialysis. Patients aged over 60 years who had newly started hemodialysis (98 cases) were studied. These were 59 men and 39 women. The age was 73 +/- 7 years (mean +/- standard deviation). In each patient, the cause of renal failure (non-diabetes/diabetes), body mass index, comorbid conditions (cerebrovascular disease, ischemic heart disease, etc.), ambulation, cognitive function, urgency of the initiation of dialysis, occurrence of access failure, marital status, younger cohabitants, and the length of stay after initiation of dialysis were surveyed. The median and the mean of the length of stay were 37 and 49 days. Because of this disparity, a normal distribution of the length of stay could not be obtained. However, the distribution was transformed to close to normal by logarithmic conversion of the number of days. We used the log-converted value as the length of stay for statistical analyses. We investigated the influence of the differences of each factor on the length of stay. The subjects were divided into two groups for each factor. The mean and standard deviation of the length of stay was calculated respectively. Comparisons were carried out by unpaired t-test. Multiple regression analysis was also performed using background factors as explanatory variables, and the length of stay as a dependent variable. The factors presented by the nominal scale were converted to dummy variables. Eight variables in the unpaired t-test and seven variables in multiple regression analysis were statistically significant. All but one variable were common to both analyses. The gender was statistically significant only in the unpaired t-test. It could be explained by close correlation of gender with marital status. Access failure and urgent initiation of dialysis were dominant factors for the prolongation of the length of stay. Ischemic heart disease, diabetes, inability to walk, impaired cognitive function, and absence of a partner also prolonged the length of stay.

Aged↗
PubMed2005

Parametric and nonparametric bootstrap methods for meta-analysis.

In a meta-analysis, the unknown parameters are often estimated using maximum likelihood, and inferences are based on asymptotic theory. It is assumed that, conditional on study characteristics included in the model, the between-study distribution and the sampling distributions of the effect sizes are normal. In practice, however, samples are finite, and the normality assumption may be violated, possibly resulting in biased estimates and inappropriate standard errors. In this article, we propose two parametric and two nonparametric bootstrap methods that can be used to adjust the results of maximum likelihood estimation in meta-analysis and illustrate them with empirical data. A simulation study, with raw data drawn from normal distributions, reveals that the parametric bootstrap methods and one of the nonparametric methods are generally superior to the ordinary maximum likelihood approach but suffer from a bias/precision tradeoff. We recommend using one of these bootstrap methods, but without applying the bias correction.

Bias↗
PubMed1975

[A statistical study of the interspike-interval distribution of cortical neurons].

Spontaneous activity was recorded extracellularly by glass microelectrodes from 54 neurons of the Gyrus sigmoideus posterior of unnarcotized and gallamine-immobilazed cats, and the sequential and nonsequential interspike-interval histograms were determined using the multi-channel analyzer CAT 400 C. The interval distributions were characterized by graphic criteria, and it was attempted to describe these distributions mathematically by four biparametric distributions, the Weibull, lognormal, gamma and normal distributions. 80% of the frequency distributions of type I (exponential), II (left skew, gamma-similar) and IV (almost symmetrical) could be assigned to these distributions, namely 43% of the lognormal distribution, 32% of the Weibull distribution, and 5% of the gamma distribution. The interval histograms of the type III (left skew, steep) and V (bimodal) could not be described by any of the distributions selected.

Animals↗
PubMed1992

[Distribution of 70 kD stress protein in the optic nerve. A comparative study between the normal and retinal dystrophic rat].

The immunolocalization of the 70 kD stress protein (SP70) was investigated and compared in the optic nerve of normal Sprague-Dawley (SD) rats and that of the Royal College of Surgeons (RCS) rat with inherited retinal dystrophy. At postnatal day 8, SP70 was present in the maturing glial cell bodies of both rat strains. At postnatal day 22, SP 70 was observed in the glial cell bodies and optic nerve fibers of both rat strains. At postnatal day 40 RCS rat, SP70 was diminished in the optic nerve fibers and glial cell bodies but was increased in the glial cell nuclei. This suggests that axonal transportation of SP70 from the retina may be reduced following retinal degeneration. In the SD optic nerve, the normal distribution of immunostaining for SP70 was preserved. Stress proteins are thought to play an important role in cellular development and survival mechanisms. It was suggested that optic nerve was damaged by the retinal degeneration in the RCS rat.

Animals↗
PubMed1989

[The status of galvanic assessment of equilibrium].

The galvanic test is the only method of localising the site of the disease in the differential diagnosis between a vestibular endorgan or neuronal lesion. The galvanic nystagmus persists even after complete destruction of the inner ear but is impaired as soon as the peripheral vestibular neurone is damaged. We investigated 30 normal subjects, 10 patients with Menière's disease and 20 patients with an acoustic neuroma. The patients had a reduced caloric response on one side. All subjects were stimulated monaural-unipolar. The photoelectronystagmograms were analysed by determining slow phase velocity. For interpretation we used the "relationship of excitability" as described recently by Mulch and Scherer for the thermal test. This procedure seems to be more accurate than the calculation of side difference of excitability as a proportion of total reaction. Furthermore we suggest basing the evaluation of galvanic test by calculating expectation regions for the logarithmic values obtained by right-left stimulation. This method assumes a two dimensional symmetric normal distribution. The parameters lay within the normal range in all patients with Menière's disease whereas they were abnormal in every subject with an acoustic neuroma.

Adult↗