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PubMed1980

Variation of ethinylestradiol blood levels among healthy women using oral contraceptives.

Data concerning ethinylestradiol (EE) blood levels among 93 healthy women using oral contraceptives are presented. Seventy-two per cent of the observed variation in EE blood levels was unexplainable on the basis of time since ingestion of the last oral contraceptive, day of menstrual cycle, race, age, weight, height, blood pressure, cigarette consumption, alcohol consumption, diurnal variation, or lifetime use of oral contraceptives.

Adult↗

PubMed2006

Variation in the diagnosis of child abuse in severely injured infants.

OBJECTIVE: Diagnosis of child abuse is difficult and may reflect patient, practitioner, and system factors. Previous studies have demonstrated potential lethal consequences if cases of abuse are missed and suggested a role for continuing medical education in improving the accuracy of diagnosis of suspected abuse. Although the majority of injured American children are treated at general hospitals, most published studies of severe injury resulting from child abuse have been conducted at children's hospitals. The objective of this study was to evaluate the role of hospital type in observed variations in the frequency of diagnosis of child physical abuse among children with high-risk injuries. METHODS: Hospital discharge data were evaluated, and adjusted rates of abuse diagnosis were reported according to hospital type. A regression model estimated the number of cases of abuse that would have been diagnosed if all hospitals identified abuse as frequently as observed at pediatric specialty hospitals. This study consisted of children who were <1 year old and admitted to US hospitals in 1997 for treatment of traumatic brain injury or femur fracture, excluding penetrating trauma or motor-vehicle-related injury. A total of 2253 weighted cases were analyzed. RESULTS: The proportion of patients with a medical diagnosis of child abuse varied widely between hospital types: 29% of the cases were diagnosed as abuse at children's hospitals compared with 13% at general hospitals. An estimated 178 infants (39% of total) with these specific injuries would have been identified as abused had they been treated at children's rather than general hospitals. CONCLUSIONS: Hospital type was associated with large variations in the frequency of diagnosis of child abuse. This variation was not related to observed differences in the patients or their injuries and may result from systematic underdiagnosis in general hospitals. This result has implications for quality-improvement programs at general hospitals, where the majority of injured children in the United States receive emergent medical care.

Adolescent↗

PubMed2002

Bone microstructure and developmental plasticity in birds and other dinosaurs.

Patterns of bone microstructure have frequently been used to deduce dynamics and processes of growth in extant and fossil tetrapods. Often, the various types of primary bone tissue have been associated with different bone deposition rates and more recently such deductions have extended to patterns observed in dinosaur bone microstructure. These previous studies are challenged by the findings of the current research, which integrates an experimental neontological approach and a paleontological comparison. We use tetracycline labeling and morphometry to study the variability of bone deposition rates in Japanese quail (Coturnix japonica) growing under different experimental conditions. We compare resulting patterns in bone microstructure with those found in fossil birds and other dinosaurs. We found that a single type of primary bone varies significantly in rates of growth in response to environmental conditions. Ranging between 10-50 microm per day, rates of growth overlap with the full range of bone deposition rates that were previously associated with different patterns of bone histology. Bone formation rate was significantly affected by environmental/experimental conditions, skeletal element, and age. In the quail, the experimental conditions did not result in formation of lines of arrested growth (LAGs). Because of the observed variation of bone deposition rates in response to variation in environmental conditions, we conclude that bone deposition rates measured in extant birds cannot simply be extrapolated to their fossil relatives. Additionally, we observe the variable incidence of LAGs and annuli among several dinosaur species, including fossil birds, extant sauropsids, as well as nonmammalian synapsids, and some extant mammals. This suggests that the ancestral condition of the response of bone to environmental conditions was variable. We propose that such developmental plasticity in modern birds may be reduced in association with the shortened developmental time during the later evolution of the ornithurine birds.

Animals↗

PubMed2000

Sequences of the waxy loci of wheat: utility in analysis of waxy proteins and developing molecular markers.

The waxy proteins from a number of genetic backgrounds of wheat and its progenitors were analyzed by SDS-PAGE. The deduced amino acid sequences of the waxy proteins of three diploid progenitor species indicated several key amino acid substitutions, which could explain the differences observed in the electrophoretic mobilities of the wheat waxy proteins. A slight difference observed in the apparent molecular weight of the WX-A1 protein of diploid and polyploid wheat was explained by amino acid substitutions or variations in predicted protein structures. Further, twelve different partial genomic clones, representing the individual waxy loci of the various diploid, tetraploid and hexaploid wheats, were isolated and compared. The results indicated significant variations in intron 4 and led to identification of sequences unique to the individual waxy genes and genomes of wheat and its proposed progenitors. The sequence variations observed have a great potential for development as molecular markers for identification of specific waxy loci and study of the various waxy mutants of wheat.

Base Sequence↗

PubMed2006

Hybridization among divergent stocks of largemouth bass (Micropterus salmoides) results in altered cardiovascular performance: the influence of genetic and geographic distance.

Animal populations exhibit wide ranges of divergence associated with both geographic and genetic distances. Here, we examined the role of crossing distance on the cardiovascular response to exhaustive exercise among differentiated stocks of largemouth bass Micropterus salmoides at 10 degrees C and 20 degrees C. Stocks of 2+ fish were produced using adults from three regions in the midwestern United States (southeastern Wisconsin, northwestern Wisconsin, and west central Minnesota) and were crossed with fish from central Illinois. Doppler flow probes were used to quantify cardiac output, heart rate, and stroke volume. Cardiac variables (both resting and maximal) were consistently lowest in pure Illinois fish relative to the F(1) interstock hybrids. Additionally, when exposed to exercise, cardiac variables for F(1) interstock hybrids required approximately 40% longer to return to resting levels compared with the pure Illinois stock. However, the time required to exhaust fish was similar across stocks. Interestingly, all of the stocks (including the interstock hybrids and pure Illinois) maintained cardiac scope. In general, the patterns observed in cardiovascular performance were consistent for both water temperatures. Multiple regression analysis was used to determine which of the divergence metrics contributed to variation in cardiovascular performance in interstock hybrids. Mitochondrial DNA data (genetic distance) were infrequently identified as a significant source of variation in cardiovascular performance. However, genetic distance data for the neutral allozyme markers revealed that these stocks have experienced significant divergence. Latitude (geographic distance) accounted for between 31% and 45% of variation observed in the recovery parameters. This study suggests that the magnitude of stock divergence is an important determinant in the degree to which cardiovascular performance of bass is altered from interstock hybridization and associated breakdown of coadapted gene complexes. Furthermore, these data suggest that translocating bass among even geographically discrete regions or among stocks with reasonable genetic similarity can result in substantial performance alterations at the F(1) generation.

Animals↗

PubMed1986

The selection limit due to the conflict between truncation and stabilizing selection with mutation.

Long-term selection response could slow down from a decline in genetic variance or in selection differential or both. A model of conflict between truncation and stabilizing selection in infinite population size is analysed in terms of the reduction in selection differential. Under the assumption of a normal phenotypic distribution, the limit to selection is found to be a function of kappa, the intensity of truncation selection, omega 2, a measure of the intensity of stabilizing selection, and sigma 2, the phenotypic variance of the character. The maintenance of genetic variation at this limit is also analyzed in terms of mutation-selection balance by the use of the "House-of-cards" approximation. It is found that truncation selection can substantially reduce the equilibrium genetic variance below that when only stabilizing selection is acting, and the proportional reduction in variance is greatest when the selection is very weak. When truncation selection is strong, any further increase in the strength of selection has little further influence on the variance. It appears that this mutation-selection balance is insufficient to account for the high levels of genetic variation observed in many long-term selection experiments.

Alleles↗

PubMed1994

Preliminary report on the validation of a grammar-based computer system for assessing skeletal maturity with the Tanner-Whitehouse 2 method.

A series of hand and wrist radiographs was assessed manually by two individuals and by a fully automated computer system for determining bone age. Assessments were repeated after 1 month to determine variability between and within the methods of bone age assessment. There was slight intra-observer variation, but complete reproducibility when assessments were made by computer. The variation between the human assessors was less than that between human and computer assessments. The difference between overall maturity scores made by the human observer and the computer system was, however, acceptably small, and the majority of assessments were the same. It is concluded this computer system for assessing bone age in normal children is reliable and accurate, but that it needs to be validated against a much larger set of radiographs.

Adolescent↗

PubMed2000

Bicycle drive system dynamics: theory and experimental validation.

Bicycle pedaling has been studied from both a motor control and an equipment setup and design perspective. In both cases, although the dynamics of the bicycle drive system may have an influence on the results, a thorough understanding of the dynamics has not been developed. This study pursued three objectives related to developing such an understanding. The first was to identify the limitations of the inertial/frictional drive system model commonly used in the literature. The second was to investigate the advantages of an inertial/frictional/compliant model. The final objective was to use these models to develop a methodology for configuring a laboratory ergometer to emulate the drive system dynamics of road riding. Experimental data collected from the resulting road-riding emulator and from a standard ergometer confirmed that the inertial/frictional model is adequate for most studies of road-riding mechanics or pedaling coordination. However, the compliant model was needed to reproduce the phase shift in crank angle variations observed experimentally when emulating the high inertia of road riding. This finding may be significant for equipment setup and design studies where crank kinematic variations are important or for motor control studies where fine control issues are of interest.

Bias↗

PubMed1987

Effect of anesthesia on glucose production and utilization in rats.

This study was undertaken to determine the effects of pentobarbital anesthesia (50 mg/kg ip) on glucose kinetics and individual tissue glucose utilization in vivo, in chronically catheterized rats. Glucose turnover studies were carried out using [3-3H]glucose as tracer. A transient hyperglycemia and an increased glucose production were observed 3 min after induction of anesthesia. However, 40 min after induction of anesthesia, glycemia returned to the level observed in awake animals, whereas glucose turnover was decreased by 30% as compared with unanesthetized rats. These results are discussed with regard to the variations observed in plasma insulin, glucagon, and catecholamine levels. Glucose utilization by individual tissues was studied by the 2-[1-3H]deoxyglucose technique. A four- to fivefold decrease in glucose utilization was observed in postural muscles (soleus and adductor longus), while in other nonpostural muscles (epitrochlearis, tibialis anterior, extensor digitorum longus, and diaphragm) and other tissues (white and brown adipose tissues) anesthesia did not modify the rate of glucose utilization. A decrease in glucose utilization was also observed in the brain.

Animals↗

PubMed1996

Geographic variation in patient surveillance after colon cancer surgery.

PURPOSE: Considerable variation among surgeons exists in the current practice of patient surveillance after colon cancer treatment. We evaluated whether geographic factors are responsible for this observed variation. METHODS: Profiles of hypothetical patients and a detailed questionnaire based on the profiles were mailed to 2,733 members of two national surgical societies. The influence of the geographic location of the respondents on practice patterns were assessed in two ways. Repeated-measures analysis of variance was used to compare the practice patterns among 19 large metropolitan statistical areas (MSAs) and chi 2 analysis was used to determine whether these patterns differed by MSA population size. RESULTS: Seven of nine commonly used surveillance modalities were ordered significantly more frequently with increasing tumor-node-metastasis (TNM) stage and significantly less frequently with year postsurgery among the 995 respondents with assessable responses, but MSA population size and geographic location of physicians generally had no effect on documented practice variability. The remaining two modalities (bone scan and computed tomography [CT]) were used so infrequently as to preclude meaningful analysis. CONCLUSION: Surveillance after potentially curative colon cancer surgery for otherwise healthy patients is not significantly affected by the geographic location of the surgeon who performs the surveillance testing and only modestly affected by the population size of the MSA in which he/she practices. These data should help in the design of prospective trials of this topic.

Analysis of Variance↗

PubMed1996

Geographic variation in the conduct of patient surveillance after lung cancer surgery.

PURPOSE: Considerable variation among surgeons exists in the current practice of patient surveillance after lung cancer treatment. We evaluated whether geographic factors are responsible for this observed variation. METHODS: Profiles of hypothetical patients suitable for postoperative surveillance and a detailed questionnaire based on the profiles were mailed to the 3,700 members of the Society of Thoracic Surgery (STS). The influence of the geographic location of the respondents on practice patterns was assessed among eight large metropolitan statistical areas (MSAs) with sufficient numbers of respondents, among nine broad geographic areas (United States census regions), and by the population size of the MSA from which the respondents reported. RESULTS: There were 2,009 responses (54% return rate); 768 of those respondents both operate on and provide long-term follow-up care for lung cancer patients. There were sizeable effects of tumor-node-metastasis (TNM) stage and year postsurgery on practice patterns. Respondents from the Los Angeles/Long Beach MSA consistently had the highest frequency of follow-up test usage and those from the Tampa/St Petersburg MSA usually had the lowest. This held true for most testing modalities and was consistent across TNM stages I to III and years 1 to 5 postsurgery. Follow-up strategy was generally most intensive in the largest MSAs (population size, 2.5 to 10 million). The STS respondents from the Pacific US census region generally used the most intensive follow-up strategies and those from the East North Central and Mountain regions often used the least intensive. The differences disclosed in all three analyses were small. CONCLUSION: There is marked variation among STS members in surveillance strategy, and the determinants of testing intensity are complex and interrelated. TNM stage and year postsurgery clearly affect follow-up practice; this analysis provides the first evidence that geographic setting has rather little effect on the surveillance strategies of clinicians.

Continuity of Patient Care↗

PubMed1984

Evaluation of the rat thyroid cell strain FRTL-5 as an in-vitro bioassay system for thyrotrophin.

The cyclic AMP response to bovine TSH was characterized in a strain of rat thyroid follicular cells ( FRTL -5) maintained in continuous culture. Significant stimulation of intracellular cyclic AMP was attained at a TSH dose of 5 muu./ml. Cyclic AMP accumulation continued to increase, at higher TSH doses, with no evidence for attainment of a maximum level at the highest dose tested (5 mu./ml). The precision of TSH measurement was better than 10% over the range 50-5000 muu./ml, comparing favourably with that observed with analogous assays based on human cells, tissue slices or membrane preparations. Using sequential subcultures of FRTL -5 cells, the between-assay variation in response to a single dose of a standard preparation of bovine TSH (53/11; 370 muu./ml) was of the order of 20% which compared favourably with the between-assay variation observed with different cultures of human thyroid cells. Prolongation of the incubation of FRTL -5 cells with TSH to 3 h revealed a progressive increase in the extracellular accumulation of cyclic AMP. Addition of TSH to resting FRTL -5 cells resulted in a stimulation of inorganic iodide uptake with pronounced bell-shaped dose-response characteristics. Thus a maximum uptake was observed at a TSH dose of 100 muu./ml with a significant reduction at higher doses. Acute stimulation of cells with TSH (100 muu./ml) resulted in a rapid and marked alteration in cell morphology, with evidence of cellular retraction and surface ruffling.

Animals↗

PubMed1979

Interlaboratory variation of leukocyte differential counts: results from the Finnish proficiency testing programme in haematological morphology, 1974-1977.

The interlaboratory variation of leukocyte differential counts in the Finnish proficiency testing programme in haematological morphology is presented. During 1974-1977 altogether twenty-four different blood smears with neither leukocytosis nor abnormal leukocytes were examined by the participants. During this period 206 laboratories participated in the voluntary programme. The interlaboratory variation of leukocyte differential counts was analyzed for band neutrophils, segmented neutrophils, eosinophils, basophils, lymphocytes and monocytes. Except for band neutrophils and monocytes the observed variations were found to closely match the known random sampling variation which is inherent in the method for estimating the proportions of the various leukocytes of peripheral blood. It is suggested that the results point to variations in the definitions to differentiate band vs. segmented neutrophils and monocytes vs. lymphocytes. Interlaboratory proficiency testing is considered to offer an effective means to investigate the quality of morphologic analyses as practised on a day to day basis in the participating laboratories.

Basophils↗

PubMed1975

[Von Eulenburg's congenital paramyotonia and aptitude for military service. Cases taken from a family with 25 cases since 1789].

The authors present four cases of von Eulenberg's paramyotonia. From the family history it was possible to follow the condition through seven generations since 1780; it confirms the autosomal dominant nature of genetic transmission, with almost complete penetrance. From the clinical standpoint, the condition observed is particularly pure, occurring exclusively in the cold. At no time were paralyses or adynamia independent of the myotonic phenomena and of temperature variations observed. The laboratory investigations carried out, ionic and enzyme, showed no abnormalities. Electromyographic study showed the presence of numerous true myotonic out-bursts, variable in shape and in amplitude, independant of the myotonic phenomenon, and present in the absence of exposure to cold. The effects of the condition on aptitude for military service are examined and in this respects the author recalls that the history of myotonia is intimately bound up with medico-military problems.

Adult↗

PubMedDate not supplied

Expression pattern of the HMGB1 gene in sarcomas of the dog.

BACKGROUND: The human high mobility group protein B1 (HMGB1) has attracted considerable interest among oncologists because it sensitises cancer cells to the anticancer drug cisplatin by shielding cisplatin-DNA adducts from nucleotide excision repair. MATERIALS AND METHODS: Since cisplatin is the cornerstone of adjuvant systemic therapy for osteosarcomas, in both humans and dogs, the expression pattern of the HMGB1 gene in seven canine sarcomas was investigated by Northern blot analysis and semi-quantitative RT-PCR. RESULTS: A strong intertumoural variation of HMGB1 expression was detected by Northern blot analysis and confirmed by the semi-quantitative RT-PCR established herein. CONCLUSION: The observed variations of HMGB1 expression in canine sarcomas emphasises the role of HMGB1 as a potential marker of clinical interest as its expression level may predict the clinical outcome of therapies based on cisplatin. The semi-quantitative RT-PCR established allows a quick and convenient determination of the HMGB1 expression level as necessary for clinical applications.

Animals↗

PubMed1983

Plasma levels of growth hormone, corticosterone and insulin, during induced hepatocyte synchronization in young rats.

A wave of synchronous hepatocytes entering the cell cycle can be obtained in vivo after a subcutaneous injection (e.g. of casein) in rats at around Post-natal Day 10, when plasma growth hormone (GH) levels reach a low plateau (40 +/- 2 ng/ml) and liver cell proliferation rate is high. The present work reports the following changes in plasma hormone concentrations after synchronization of 20% of the hepatocyte population: (1) during the G1 phase (i.e. 6-12 hr after the mitogenic trigger), plasma GH concentration has dropped further (25 +/- 1.5 ng/ml). It was back to 90% of control levels during the S phase, mitosis and the following response including a transitory decrease in labelling index below control values. Injected together with the irritating mitotic trigger, a single dose of rat GH reduced the cell synchronization and post-synchronization effects by 50%. (2) Plasma corticosterone levels varied inversely to those of GH, increasing to twice the control values during G1 and were back to physiological levels when synchronized hepatocytes entered the S phase. (3) Variations in insulin levels were similar to that of corticosterone, with narrower ranges and reduced amplitudes. Our data suggest a possible correlation between the observed variations in plasma hormone levels and the induced synchronous hepatocyte response.

Animals↗

PubMed2004

Contribution of the LRP5 gene to normal variation in peak BMD in women.

UNLABELLED: The role of the LRP5 gene in rare BMD-related traits has recently been shown. We tested whether variation in this gene might play a role in normal variation in peak BMD. Association between SNPs in LRP5 and hip and spine BMD was measured in 1301 premenopausal women. Only a small proportion of the BMD variation was attributable to LRP5 in our sample. INTRODUCTION: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene have been implicated as the cause of multiple distinct BMD-related rare Mendelian phenotypes. We sought to examine whether the LRP5 gene contributes to the observed variation in peak BMD in the normal population. MATERIALS AND METHODS: We genotyped 12 single nucleotide polymorphisms (SNPs) in LRP5 using allele-specific PCR and mass spectrometry methods. Linkage disequilibrium between the genotyped LRP5 SNPs was measured. We tested for association between these SNPs and both hip and spine BMD (adjusted for age and body weight) in 1301 healthy premenopausal women who took part in a sibling pair study aimed at identifying the genes underlying peak bone mass. Our study used both population-based (ANOVA) and family-based (quantitative transmission disequilibrium test) association methodology. RESULTS AND CONCLUSIONS: The linkage disequilibrium pattern and haplotype block structure within the LRP5 gene were consistent with that observed in other studies. Although significant evidence of association was found between LRP5 SNPs and both hip and spine BMD, only a small proportion of the total variation in these phenotypes was accounted for. The genotyped SNPs accounted for approximately 0.8% of the variation in femoral neck BMD and 1.1% of the variation in spine BMD. Results from our sample suggest that natural variation in and around LRP5 is not a major contributor to the observed variability in peak BMD at either the femoral neck or lumbar spine in white women.

Adult↗

PubMed1986

Bronchodilator response in chronic obstructive pulmonary disease.

We measured response to 250 micrograms isoproterenol in 985 patients with COPD who were carefully studied and followed closely for nearly 3 yr. Response was quantitated in relative (% increase in FEV1) and absolute (change in FEV1 as a % predicted normal) terms. Patients were told to abstain from bronchodilator for 6 h before testing, and responses were larger in those who said they had done this. Responses were not related to blood theophylline concentrations. In patients who had abstained for 6 h, response averaged 15% of the baseline FEV1 or 5% of the predicted normal FEV1. Relative response was inversely proportional to baseline FEV1, whereas absolute response was directly related to baseline FEV1. Responses were positively related to symptomatic wheezing and exercise capacity, and negatively to smoking history, but these features accounted for little of the observed variation in response. Patients with large relative and absolute responses demonstrated increased variability of FEV1 with time and a decreased annual rate of decline of FEV1. There was little change in response with time, and the change observed could probably be explained by a gradual decrease in FEV1. However, time-related interindividual and intraindividual variations of response were large and impossible to separate from random variations of FEV1.

Adult↗