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Criteria for exchange transfusion in jaundiced newborns.

OBJECTIVE: A widely published set of exchange transfusion criteria lowers critical bilirubin concentrations when the serum albumin falls to < 2.5 g/dL. Although acknowledging the role of bilirubin-albumin binding in bilirubin neurotoxicity, this approach may inadvertently produce two critical bilirubin concentrations. This study investigates using the bilirubin/albumin ratio instead of the single albumin concentration to eliminate this potential ambiguity in the criteria. DESIGN AND PARTICIPANTS: The bilirubin/albumin ratio was defined as a reliable indicator of bilirubin-albumin binding if the frequency curves of specific unbound bilirubin concentrations are normally distributed functions of the ratio. Therefore the bilirubin/albumin ratios at which the unbound bilirubin reached 10, 15, and 20 nmol/L were determined by the peroxidase method in 35 well full-term, 10 ill full-term, and 19 ill preterm neonates. The frequency curves for each unbound bilirubin concentration plotted against the bilirubin/albumin ratio were tested for normality. RESULTS: The frequency of each unbound bilirubin concentration was a normally distributed function of the bilirubin/albumin ratio. Furthermore, the mean ratio at which each unbound bilirubin occurred did not differ significantly among the groups of neonates. CONCLUSION: The bilirubin/albumin ratio is a simple, nonambiguous way of incorporating the serum albumin concentration into exchange transfusion criteria.

Bilirubin↗

Normative sleep data, cognitive function and daily living activities in older adults in the community.

STUDY OBJECTIVES: To present normative data of sleep-wake characteristics and to examine risk factors associated with extreme values (i.e., in the 5 lower and upper percentiles of the distribution) in older adults. DESIGN: Cross-sectional telephone survey SETTING: The metropolitan area of Paris, France. PARTICIPANTS: A total of 7010 randomly selected households were contacted. Among them, 1264 households included at least 1 resident 60 years of age or older; 1026 subjects agreed to participate (participation rate: 80.9%). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Subjects were interviewed with the Sleep-EVAL System about their sleeping habits and sleep and psychiatric disorders. In addition, the system administered to all the participants the Psychological General Well-Being Schedule, the Cognitive Difficulties Scale (Mac Nair-R), and an independent living scale. The median nighttime sleep duration was 7 hours without significant difference between the age groups. Factors positively associated with the 5 percentile (4 hours 30 minutes or less) of nighttime sleep duration were obesity, poor health, insomnia, and insomnia accompanied by daytime sleepiness and cognitive impairment. At the other extremity (95th percentile), long sleep (9 hours 30 minutes or more) was associated with organic disease, lack of physical exercise, and lower education. A daytime sleep duration of 1 hour or more (95th percentile) was associated with being a man, cognitive impairment, high blood pressure, obesity, and insomnia. Long sleep latency (95th percentile at 80 minutes) was associated with anxiety, lower education, poor health, insomnia without excessive daytime sleepiness, and obstructive sleep apnea syndrome. Obesity and loss of autonomy in activities of daily living was associated with both early (9 PM or earlier) and late bedtime (1 AM or later) and early (< or = 5 AM) and late (> or = 9 AM) wake-up time. CONCLUSIONS: This study illustrates the usefulness of normal distributions of sleep parameters in the general population to calculate different risk factors associated with extreme values of the normal distribution.

Activities of Daily Living↗

[Characteristics and distribution of normal human epidural fat].

Epidural fat provides sufficient cushion for the pulsatile movements of the dural sac, protects nerve structures, facilitates the movement of the dural sac over the periosteum of the spinal column during flexion and extension, and forms a pharmacologic reservoir of lipophilic substances. We review epidural fat and related structures, including their development during the fetal period when the epidural space is filled by undifferentiated loose, areolar mesenchymal tissue that surrounds the dural sac. In the adult, epidural fat has a continuous distribution and follows a certain metameric pattern. It is located mainly on the dorsal side of the epidural space, where it is organized in triangular capsules joined to the midline of the ligamentum flavum by a vascular pedicle. We consider the distribution of epidural fat in the axial and sagittal planes; its presence in the anterior, lateral and posterior epidural space; its presence in the cervical, thoracic and lumbar portions of the spinal column; and its characteristics and variations according to differing body habits and sex. Finally, we speculate on the possible anesthetic implications of epidural fat in terms of the pharmacokinetics of drugs injected into the epidural space and the tasks of locating the epidural space and inserting an epidural catheter during anesthetic procedures.

Adipocytes↗

Subcellular distribution of normal and mutant vitamin D receptors in living cells. Studies with a novel fluorescent ligand.

To understand the subcellular localization of the vitamin D receptor (VDR) and to measure VDR content in single cells, we recently developed a fluorescent labeled ligand, 4,4-difluoro-4-bora-3a, 4a-diaza-s-indacene (BODIPY)-calcitriol. This tagged hormone has intact biological activity, high affinity and specific binding to the receptor, and enhanced fluorescent emission upon receptor binding. Using BODIPY-calcitriol, here we monitored the subcellular distribution of VDR in living cultured cells by microscopy. Time course studies showed that an equilibrium between the cytoplasmic and nuclear hormone binding developed within 5 min and was maintained thereafter. We found a substantial proportion of VDR residing in the cytoplasm, colocalized with endoplasmic reticulum, the Golgi complex, and microtubules. Confocal microscopy clarified the presence of VDR within discrete regions of the nucleus and along the nuclear envelope. There was no VDR in the plasma membrane. Low affinity BODIPY-calcitriol binding sites were in the mitochondria. Mutations in the VDR gene selectively and specifically altered BODIPY-calcitriol distribution. Defects in the hormone binding region of VDR prevented both nuclear and cytoplasmic hormone binding. Defects in the DNA binding region decreased the nuclear retention of VDR and prevented localization to nuclear foci. These results with BODIPY-calcitriol reveal cytoplasmic VDR localization in living cells and open the possibility of studying the three-dimensional architecture of intranuclear target sites.

Boron Compounds↗

An examination of the robustness of the empirical Bayes and other approaches for testing main and interaction effects in repeated measures designs.

In a previous paper, Boik presented an empirical Bayes (EB) approach to the analysis of repeated measurements. The EB approach is a blend of the conventional univariate and multivariate approaches. Specifically, in the EB approach, the underlying covariance matrix is estimated by a weighted sum of the univariate and multivariate estimators. In addition to demonstrating that his approach controls test size and frequently is more powerful than either the epsilon-adjusted univariate or multivariate approaches, Boik showed how conventional multivariate software can be used to conduct EB analyses. Our investigation examined the Type I error properties of the EB approach when its derivational assumptions were not satisfied as well as when other factors known to affect the conventional tests of significance were varied. For comparative purposes we also investigated procedures presented by Huynh and by Keselman, Carriere, and Lix, procedures designed for non-spherical data and covariance heterogeneity, as well as an adjusted univariate and multivariate test statistic. Our results indicate that when the response variable is normally distributed and group sizes are equal, the EB approach was robust to violations of its derivational assumptions and therefore is recommended due to the power findings reported by Boik. However, we also found that both the EB approach and the adjusted univariate and multivariate procedures were prone to depressed or elevated rates of Type I error when data were non-normally distributed and covariance matrices and group sizes were either positively or negatively paired with one another. On the other hand, the Huynh and Keselman et al. procedures were generally robust to these same pairings of covariance matrices and group sizes.

Bayes Theorem↗

Quantitative risk assessment of Campylobacter spp. in poultry based meat preparations as one of the factors to support the development of risk-based microbiological criteria in Belgium.

The objective of this study was to do an exercise in risk assessment on Campylobacter spp. for poultry based meat preparations in Belgium. This risk assessment was undertaken on the demand of the competent national authorities as one of the supportive factors to define risk-based microbiological criteria. The quantitative risk assessment model follows a retail to table approach and is divided in different modules. The contamination of raw chicken meat products (CMPs) was represented by a normal distribution of the natural logarithm of the concentration of Campylobacter spp. (ln[Camp]) in raw CMPs based on data from surveillance programs in Belgium. To analyse the relative impact of reducing the risk of campylobacteriosis associated with a decrease in the Campylobacter contamination level in these types of food products, the model was run for different means and standard deviations of the normal distribution of the ln[Camp] in raw CMPs. The limitation in data for the local situation in Belgium and on this particular product and more precisely the semi-quantitative nature of concentration of Campylobacter spp. due to presence/absence testing, was identified as an important information gap. Also the knowledge on the dose-response relationship of Campylobacter spp. was limited, and therefore three different approaches of dose-response modelling were compared. Two approaches (1 and 2), derived from the same study, showed that the reduction of the mean of the distribution representing the ln[Camp] in raw CMPs is the best approach to reduce the risk of Campylobacter spp. in CMPs. However, for the simulated exposure and approach 3 it was observed that the reduction of the standard deviation is the most appropriate technique to lower the risk of campylobacteriosis. Since the dose-response models used in approach 1 and 2 are based on limited data and the reduction of the mean corresponds with a complete shift of the contamination level of raw CMPs, demanding high efforts from the poultry industry, it is proposed to lower the standard deviation of the concentration of Campylobacter spp. in raw CMPs. This proposal corresponds with the elimination of the products that are highly contaminated. Simulation showed that eating raw chicken meat products can give rise to exposures that are 10(10) times higher than when the product is heated, indicating that campaigns are important to inform consumers about the necessity of an appropriate heat treatment of these type of food products.

Animals↗

Clinical and haematological data in 254 cases of beta-thalassaemia trait in Italy.

The haematological and clinical data in 254 Italian subjects with beta-thalassaemia trait are reported. 46% of the patients were anaemic, 40% complained of weakness, 19% showed enlargement of the spleen and 10% enlargement of the liver. The haemoglobin levels ranged from 8 to 15.5 g/dl with a normal distribution and a mean of 12.73 for males, 10.93 for females and 11.34 for children (4-15 years). Reticulocyte counts and serum bilirubin levels were slightly increased and both showed a statistically significant relationship with haemoglobin levels. The serum iron level was increased in 27% and decreased in 6% of the cases. Haemoglobin A2 concentrations ranged from 3.5% to 8% with a normal distribution and a mean of 5.37; Hb F values were less than 1% in 36% and varied from 1 to 14% in the remainder. Red cell osmotic fragility was decreased in all but 6% of the subjects: low MCV, MCH and MCHC values were observed in 75%, 86% and 10% respectively. A comparison is made between the data and those obtained by other workers.

Adolescent↗

Neonatal protein C: molecular composition and distribution in normal term infants.

Protein C (PC) is a vitamin K-dependent serine protease which functions as the central regulatory protein with both anticoagulant and profibrinolytic properties. The PC levels in healthy term newborns are approximately one third of adult levels. Severely decreased levels of PC are seen in sick term and preterm infants. These neonates appear to have an increased incidence of thrombosis. Undetectable levels of PC are found in homozygous PC deficient infants with DIC and purpura fulminans symptoms. In this present study we report the composition and distribution of PC in term newborn and compare the results with adult values. Plasma was obtained from placental cord blood of 20 healthy term (38-42 weeks gestation) infants. PC was immunopurified, run on SDS-PAGE, and immuno-blotted. The composition of the PC molecule in neonatal plasma is identical to that seen in adults. Using densitometry to determine the distribution of the PC components, we observed a 2-fold increase in single chain PC in the neonate as compared to the adult. In the neonate, there was an inverse correlation between the level of total PC antigen and the amount of single chain. These findings suggest the possibility that the processing of PC may be developmentally influenced.

Female↗

Osteonectin mRNA: distribution in normal and transformed cells.

Overlapping cDNA clones encoding bovine osteonectin were isolated from a lambda gt11 expression library constructed from bovine bone cell mRNA. The longest clone, lambda On 17 (insert size 2.0 kb) was studied in detail. The clone was shown to encode osteonectin by hybrid select translation experiments and by DNA sequence analysis. Northern analysis of bone cell RNA showed the length of the osteonectin mRNA to be 2.0 kb. Osteonectin message was found in bone but not in soft tissue (liver and brain) preparations consistent with the distribution of the protein in these tissues. On the other hand, osteonectin message was observed in tendon, a tissue in which little or no osteonectin protein is found in vivo. Hybridization of osteonectin cDNA was detected in cells from a number of species including human, rat, mouse and chick. The level of osteonectin mRNA was drastically decreased in chick embryo fibroblasts transformed by Rous sarcoma virus.

Animals↗

Single coronary artery: a familial clustering.

A 59 year old man undergoing investigation for chest pain was found at elective coronary angiography to have a single coronary artery; the left coronary had a normal distribution, with the right coronary originating as a continuation of the atrioventricular circumflex. His 30 year old daughter was admitted for elective coronary angiography for further investigation of a dilated cardiomyopathy. She was also found to have a single coronary artery. However, in her case, the right and left coronary arteries arose from the right sinus of Valsalva; the right coronary had a normal distribution, the left coronary passed anterior to the pulmonary trunk and aorta.

Adult↗

Utility of TICS-M for the assessment of cognitive function in older adults.

BACKGROUND: Routine screening of high-risk elderly people for early cognitive impairment is constrained by the limitations of currently available cognitive function tests. The Telephone Interview of Cognitive Status is a novel instrument for assessment of cognitive function that can be administered in person or by telephone. OBJECTIVE: To evaluate the determinants and utility of TICS-M (13-item modified version) for assessment of cognitive function in healthy elderly people. METHODS: The utility of TICS-M was compared with more widely used MMSE and CAMCOG in a cross-sectional survey of 120 older (62 to 89 years) UK adults. RESULTS: The TICS-M cognitive test scores (27.97, SD 4.15) were normally distributed in contrast with those for MMSE and CAMCOG that had a negatively skewed distribution. TICS-M scores were inversely correlated with age (r = -0.21) and with the NART fullscale IQ (r = -0.35), but were independent of years of education in this cohort. TICS-M was highly correlated with MMSE (r = 0.57) and with CAMCOG (r = 0.62) scores. The time required to complete the test is comparable to MMSE and substantially less than CAMCOG. CONCLUSIONS: The normal distribution of TICS-M test scores suggest that this test is less constrained by the ceiling effect which limits the utility of MMSE and CAMCOG test scores in detecting early cognitive impairment. TICS-M is an appropriate instrument to assess cognitive function in both research and in clinical practice.

Aged↗

[Frequency distribution of birth weight and gestational age in Taiwan].

Perinatal mortality rate is closely related to birth weight. We collected data on 35919 single liveborn babies at a teaching hospital in central Taiwan between 1977 and 1987, excluding 1980. The average birth weights of the two sexes combined, and of male and female live births separately, were 3163 +/- 486 gm, 3211 +/- 499 gm (N = 18865) and 3110 +/- 466 gm (N = 17054), respectively. The average gestational age of these live births was 39.7 +/- 2.1 weeks. The skewness and kurtosis of birth weight and gestational age distribution were -0.86 and 3.13, and -2.11 and 10.29, respectively. The two distributions indicated high kurtosis and left skewness, and were approximately normally distributed. Because birth weight and gestational age are highly associated, the skew-to-left residual distribution of birth weight might have been induced by low gestational age. Babies of low gestational age might not be able to develop mature organs and tissues, which, thus, results in high perinatal mortality. The distribution of birth weight intersects the normal curve within the region between 1500 gm and 2000 gm, which means that we may divide it into a predominant part and a residual part. Many articles have shown that the residual part is highly correlated to perinatal mortality rate and deserves further analysis. The average birth weight with gestational age at 40 weeks was 3239 +/- 385 gm, skewness and kurtosis were 0.16 and 0.75, respectively. The birth-weight distribution for a given number of gestational weeks is closer to the normal distribution. This paper provides standard figures and tables of birth weight with specific gestational age as a norm for related medical research.

Birth Weight↗

Comparison of epidermal growth factor binding and receptor distribution in normal human epidermis and epidermal appendages.

To localize epidermal growth factor (EGF) receptors in normal human epidermis and other skin structures, two different light microscopic methods were used. EGF binding [( 125I]EGF/R) to the extracellular portion of the EGF receptor was studied by incubating intact skin samples with [125I]EGF, sectioning the tissues, and performing autoradiography. Immunoreactive EGF receptor molecules (IR-EGF/R) were localized with a mono-specific anti-EGF receptor antibody using a 2-step indirect immunocytochemical method (horseradish peroxidase) and detergent permeabilized tissues. This latter method measured the total pool of EGF receptors: occupied and/or internalized forms, precursor forms, and partially degraded forms of the EGF receptor that retain immunoreactivity. Both the [125I]EGF/R and IR-EGF/R localization studies indicated that EGF receptors were present in basal epidermal keratinocytes, sebocytes, outer root sheath cells in hair follicles, smooth muscle cells of arrector pili muscles, and dermal arteries. The highest levels of [125I]EGF/R and IR-EGF/R were found in the dermal ducts of eccrine sweat glands. The distribution of both [125I]EGF/R and IR-EGF/R was not consistent with the concept that EGF exclusively is involved in cellular division and proliferation in normal human epidermis and its appendages, i.e., EGF receptors were also found in tissues that do not undergo rapid proliferation. The present study indicates that EGF may have a more complex regulatory role in the skin than was previously thought.

Autoradiography↗

Exhaled nitric oxide measurements in a population sample of young adults.

In epidemiologic studies of asthma there is a group with recent wheeze, but with no airway hyperresponsiveness (AHR), in whom it is unclear whether any significant airway abnormality exists. Exhaled nitric oxide (NO) has been proposed as a measure of airway inflammation. We measured exhaled NO in a population sample of 306 young adults who also underwent bronchial challenge with histamine or a bronchodilator test. Subjects blew into a 3-L Tedlar bag against a 2-mm-diameter resistance to close the soft palate and exclude nasal air. The NO content of expired gas from a single breath was analyzed by chemiluminescent analyzer. Exhaled NO was log-normally distributed in the population sample and duplicate measurements were highly reproducible (intraclass correlation coefficient = 0.98). Exhaled NO correlated significantly with airway responsiveness, measured as the dose-response ratio to histamine (r = 0.39, p < 0.001) and with peripheral blood eosinophils (r = 0.35, p < 0.001). Exhaled NO was significantly greater in asthmatic subjects (geometric mean, 22.2; 95% confidence intervals, 16.1 to 30. 7 ppb) than in normal subjects (7.8, 7.1 to 8.4, p < 0.001) or in subjects with wheeze but no AHR (8.8, 7.5 to 10.3, p < 0.001). We conclude that exhaled NO is log-normally distributed, is highly reproducible and discriminates well among subjects, suggesting that it is both a feasible and useful measurement for epidemiologic studies of asthma. The findings suggest that wheeze in the absence of AHR is unlikely to be associated with airway inflammation.

Adult↗

Comparing decision bound and exemplar models of categorization.

The performance of a decision bound model of categorization (Ashby, 1992a; Ashby & Maddox, in press) is compared with the performance of two exemplar models. The first is the generalized context model (e.g., Nosofsky, 1986, 1992) and the second is a recently proposed deterministic exemplar model (Ashby & Maddox, in press), which contains the generalized context model as a special case. When the exemplars from each category were normally distributed and the optimal decision bound was linear, the deterministic exemplar model and the decision bound model provided roughly equivalent accounts of the data. When the optimal decision bound was non-linear, the decision bound model provided a more accurate account of the data than did either exemplar model. When applied to categorization data collected by Nosofsky (1986, 1989), in which the category exemplars are not normally distributed, the decision bound model provided excellent accounts of the data, in many cases significantly outperforming the exemplar models. The decision bound model was found to be especially successful when (1) single subject analyses were performed, (2) each subject was given relatively extensive training, and (3) the subject's performance was characterized by complex suboptimalities. These results support the hypothesis that the decision bound is of fundamental importance in predicting asymptotic categorization performance and that the decision bound models provide a viable alternative to the currently popular exemplar models of categorization.

Adult↗

Normal FDG distribution patterns in the head and neck: PET/CT evaluation.

PURPOSE: To retrospectively evaluate the distribution of fluorine 18 fluorodeoxyglucose (FDG) in the head and neck region with combined positron emission tomography-computed tomography (PET/CT) in patients with no known abnormality in this region. MATERIALS AND METHODS: The institutional review board allowed a retrospective review of PET/CT images obtained in 78 patients with non-head and neck cancer and waived the requirement for informed consent. The accumulation of FDG in 11 normal head and neck structures was visually and quantitatively assessed retrospectively. Positive rate percentage (PRP) was defined as the sum of the percentages of patients with grade 2 and grade 3 tracer uptake intensity. Standardized uptake values (SUVs) were calculated for quantitative analysis. Mean SUVs were compared between the male and female patients by using the unpaired t test, and the correlation between FDG uptake and patient age was assessed by using the Pearson correlation coefficient test. RESULTS: Intense tracer uptake was usually seen in the palatine tonsils (PRP, 98%; mean SUV, 3.48), soft palate (PRP, 96%; mean SUV, 3.13), and lingual tonsils (PRP, 96%; mean SUV, 3.11). In the inferior concha (PRP, 4%; mean SUV, 1.56), thyroid gland (PRP, 3%; mean SUV, 1.31), and tongue (PRP, 1%; mean SUV, 1.39), uptake was typically minimal. FDG accumulation was variable in the sublingual glands (PRP, 72%; mean SUV, 2.93), spinal cord (PRP, 64%; mean SUV, 2.12), submandibular glands (PRP, 53%; mean SUV, 2.11), parotid glands (PRP, 51%; mean SUV, 1.90), and vocal cords (PRP, 19%; mean SUV, 1.77). The mean normal-tissue SUV in the soft palate was higher in male than in female patients (P <.01). A negative correlation between age and physiologic FDG uptake was seen in the palatine tonsils (r=-0.51, P <.001) and sublingual glands (r=-0.70, P <.001). CONCLUSION: Intense FDG uptake was usually observed in the palatine tonsils, lingual tonsils, and soft palate, whereas uptake in the major salivary glands was variable.

Adolescent↗

An accurate method for estimating an approximate lethal dose with few animals, tested with a Monte Carlo procedure.

A reliable but not necessarily precise indication of the toxicity of a chemical product is frequently needed for the determination of its class of toxicity. Estimations of the LD50 carried out for this purpose often have a precision which is higher than necessary and so is the number of laboratory animals used. Alternative methods estimating an approximate lethal dose (ALD) have been proposed, but too little is known about their accuracy and precision. The method of Deichmann and LeBlanc (1943) for estimating an ALD has a systematic error, dependent upon the magnitude of the unknown variance of the log tolerance. A new method was developed in which this systematic error was removed. Its performance was tested in a model with Monte Carlo techniques. The model is based on the log-normal distribution of individual tolerance, i.e. the lowest dose that is lethal for an individual of the species under study. A hypothetical substance was created with a mean tolerance between 1 and 5,000 mg per kg and a standard deviation of log tolerance between 0.1 and 1.5 (in natural logarithms). This substance was then subjected to a sequential test, by repeatedly drawing a random element from the population of normally distributed log tolerance values and testing whether this element is smaller or greater than the dose administered according to the method's protocol. The method of Lorke (1983) was tested with a similar simulation model. In series of 100 simulations no systematic error was found. For a standard deviation of log tolerance exceeding 0.85 the new method was less precise than that of Lorke, but for smaller values the new method was more precise; it required on average less than ten animals, against 13 required in Lorke's method.

Animals↗

Distribution and correlation of events during thermal inactivation of Bacillus megaterium spores.

Aqueous suspensions of Bacillus megaterium QM B1551 spores were heated at temperatures from 75 to 85 C. The rapid initial viability loss, followed by a more gradual, almost exponential decline, was not due to mixed populations with discrete heat resistances. The slight "tailing" below 0.01% survival was not the result of heat adaptation. Loss of viability was more rapid than loss of dipicolinic acid (DPA) and germinability and, although these events could not be correlated by use of simple kinetic plots, they had similar activation energies (80 to 90 kcal/mole). Probability (probit) plots of per cent survival as a function of logarithmic time yielded not the single line expected, if the heat resistances of individuals in the population were log-normally distributed, but two straight lines intersecting at a survival level of 1 to 6%. Probit-intersects occurred at times ranging from 8 min for spores heated at 85 C, to 310 min at 75 C. Probit-intersects for DPA release and loss in germinability occurred at the same time as for survival, but at much higher levels of retention. There appeared to be two subpopulations, both log-normally distributed but with different mechanisms of kill. Ninety-four to 99% of the spores died via injury to the cell-division process but retained germinability; the remaining smaller subpopulation (1 to 6%) was nonviable because of loss of the ability to germinate.

Bacillus megaterium↗