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Biomedical subjects

S Brauer

Publications and source records attributed to S Brauer.

At least 19 recordsLinked to original sources

Breath alcohol concentration determined with a new analyzer using free exhalation predicts almost precisely the arterial blood alcohol concentration.

A new breath alcohol (ethanol) analyzer has been developed, which allows free exhalation, standardizes measured exhaled alcohol concentration to fully saturated water vapor at a body temperature of 37 degrees C (43.95 mg/L) and includes a built-in self-calibration system. We evaluated the performance of this instrument by comparing standardized alcohol concentration in freely expired breath (BrAC) with arterial (ABAC) and venous (VBAC) blood alcohol concentrations in fifteen healthy volunteers who drank 0.6 g of alcohol per kg body weight. The precision (coefficient of variation, CV) of the analyzer based on in vivo duplicate measurements in all phases of the alcohol metabolism was 1.7%. The ABAC/BrAC ratio was 2251+/-46 (mean+/-S.D.) in the post-absorptive phase and the mean bias between ABAC and BrAC x 2251 was 0.0035 g/L with 95% limits of agreement of 0.033 and -0.026. The ABAC and BrAC x 2251 were highly correlated (r=0.998, p<0.001) and the regression relationship was ABAC = 0.00045 + 1.0069 x (BrAC x 2251) indicating excellent agreement and no fixed or proportional bias. In the absorption phase, ABAC exceeded BrAC x 2251 by at most 0.04+/-0.03 g/L when tests were made at 10 min post-dosing (p<0.05). The VBAC/BrAC ratio never stabilized and varied continuously between 1834 and 3259. There was a proportional bias between VBAC and BrAC x 2251 (ABAC) in the post-absorptive phase (p<0.001). The pharmacokinetic analysis of the elimination rates of alcohol and times to zero BAC confirmed that BrAC x 2251 and ABAC agreed very well with each other, but not with VBAC (p<0.001). We conclude that this new breath analyzer using free exhalation has a high precision for in vivo testing. The BrAC reflects very accurately ABAC in the post-absorption phase and substantially well in the absorption phase and thereby reflects the concentration of alcohol reaching the brain. Our findings highlight the magnitude of arterio-venous differences in alcohol concentration and support the use of breath alcohol analyzers as a stand-alone test for medical and legal purposes.

Adult↗

Independent histories of human Y chromosomes from Melanesia and Australia.

To investigate the origins and relationships of Australian and Melanesian populations, 611 males from 18 populations from Australia, Melanesia, and eastern/southeastern Asia were typed for eight single-nucleotide polymorphism (SNP) loci and seven short tandem-repeat loci on the Y chromosome. A unique haplotype, DYS390.1del/RPS4Y711T, was found at a frequency of 53%-69% in Australian populations, whereas the major haplotypes found in Melanesian populations (M4G/M5T/M9G and DYS390.3del/RPS4Y711T) are absent from the Australian populations. The Y-chromosome data thus indicate independent histories for Australians and Melanesians, a finding that is in agreement with evidence from mtDNA but that contradicts some analyses of autosomal loci, which show a close relationship between Australian and Melanesian (specifically, highland Papua New Guinean) populations. Since the Australian and New Guinean landmasses were connected when first colonized by humans > or =50,000 years ago but separated some 8,000 years ago, a possible way to reconcile all the genetic data is to infer that the Y-chromosome and mtDNA results reflect the past 8,000 years of independent history for Australia and New Guinea, whereas the autosomal loci reflect the long preceding period of common origin and shared history. Two Y-chromosome haplotypes (M119C/M9G and M122C/M9G) that originated in eastern/southeastern Asia are present in coastal and island Melanesia but are rare or absent in both Australia and highland Papua New Guinea. This distribution, along with demographic analyses indicating that population expansions for both haplotypes began approximately 4,000-6,000 years ago, suggests that these haplotypes were brought to Melanesia by the Austronesian expansion. Most of the populations in this study were previously typed for mtDNA SNPs; population differentiation is greater for the Y chromosome than for mtDNA and is significantly correlated with geographic distance, a finding in agreement with results of similar analyses of European populations.

Asia, Southeastern↗

Melanesian origin of Polynesian Y chromosomes.

BACKGROUND: Two competing hypotheses for the origins of Polynesians are the 'express-train' model, which supposes a recent and rapid expansion of Polynesian ancestors from Asia/Taiwan via coastal and island Melanesia, and the 'entangled-bank' model, which supposes a long history of cultural and genetic interactions among Southeast Asians, Melanesians and Polynesians. Most genetic data, especially analyses of mitochondrial DNA (mtDNA) variation, support the express-train model, as does linguistic and archaeological evidence. Here, we used Y-chromosome polymorphisms to investigate the origins of Polynesians. RESULTS: We analysed eight single nucleotide polymorphisms (SNPs) and seven short tandem repeat (STR) loci on the Y chromosome in 28 Cook Islanders from Polynesia and 583 males from 17 Melanesian, Asian and Australian populations. We found that all Polynesians belong to just three Y-chromosome haplotypes, as defined by unique event polymorphisms. The major Y haplotype in Polynesians (82% frequency) was restricted to Melanesia and eastern Indonesia and most probably arose in Melanesia. Coalescence analysis of associated Y-STR haplotypes showed evidence of a population expansion in Polynesians, beginning about 2,200 years ago. The other two Polynesian Y haplotypes were widespread in Asia but were also found in Melanesia. CONCLUSIONS: All Polynesian Y chromosomes can be traced back to Melanesia, although some of these Y-chromosome types originated in Asia. Together with other genetic and cultural evidence, we propose a new model of Polynesian origins that we call the 'slow-boat' model: Polynesian ancestors did originate from Asia/Taiwan but did not move rapidly through Melanesia; rather, they interacted with and mixed extensively with Melanesians, leaving behind their genes and incorporating many Melanesian genes before colonising the Pacific.

Asia↗

Characteristics and frequency of germline mutations at microsatellite loci from the human Y chromosome, as revealed by direct observation in father/son pairs.

A number of applications of analysis of human Y-chromosome microsatellite loci to human evolution and forensic science require reliable estimates of the mutation rate and knowledge of the mutational mechanism. We therefore screened a total of 4,999 meioses from father/son pairs with confirmed paternity (probability >/=99. 9%) at 15 Y-chromosomal microsatellite loci and identified 14 mutations. The locus-specific mutation-rate estimates were 0-8. 58x10-3, and the average mutation rate estimates were 3.17x10-3 (95% confidence interval [CI] 1.89-4.94x10-3) across 8 tetranucleotide microsatellites and 2.80x10-3 (95% CI 1.72-4.27x10-3) across all 15 Y-chromosomal microsatellites studied. Our data show a mutational bias toward length increase, on the basis of observation of more repeat gains than losses (10:4). The data are in almost complete agreement with the stepwise-mutation model, with 13 single-repeat changes and 1 double-repeat change. Sequence analysis revealed that all mutations occurred in uninterrupted homogenous arrays of >/=11 repeats. We conclude that mutation rates and characteristics of human Y-chromosomal microsatellites are consistent with those of autosomal microsatellites. This indicates that the general mutational mechanism of microsatellites is independent of recombination.

Adolescent↗

Predicting the probability for falls in community-dwelling older adults using the Timed Up & Go Test.

BACKGROUND AND PURPOSE: This study examined the sensitivity and specificity of the Timed Up & Go Test (TUG) under single-task versus dual-task conditions for identifying elderly individuals who are prone to falling. SUBJECTS: Fifteen older adults with no history of falls (mean age=78 years, SD=6, range=65-85) and 15 older adults with a history of 2 or more falls in the previous 6 months (mean age=86.2 years, SD=6, range=76-95) participated. METHODS: Time taken to complete the TUG under 3 conditions (TUG, TUG with a subtraction task [TUGcognitive], and TUG while carrying a full cup of water [TUGmanual]) was measured. A multivariate analysis of variance and discriminant function and logistic regression analyses were performed. RESULTS: The TUG was found to be a sensitive (sensitivity=87%) and specific (specificity=87%) measure for identifying elderly individuals who are prone to falls. For both groups of older adults, simultaneous performance of an additional task increased the time taken to complete the TUG, with the greatest effect in the older adults with a history of falls. The TUG scores with or without an additional task (cognitive or manual) were equivalent with respect to identifying fallers and nonfallers. CONCLUSION AND DISCUSSION: The results suggest that the TUG is a sensitive and specific measure for identifying community-dwelling adults who are at risk for falls. The ability to predict falls is not enhanced by adding a secondary task when performing the TUG.

Accidental Falls↗

Lateral reach: a clinical measure of medio-lateral postural stability.

BACKGROUND AND PURPOSE: Medio-lateral postural instability has recently been identified as a risk factor for falls in the elderly community-dwelling population. However, few clinical tests involve challenges to stability limits in the medio-lateral direction. A lateral reach test was thus developed. Preliminary evaluation of the symmetry, accuracy, test-retest repeatability, and construct validity of the lateral reach test was undertaken to ensure its validity and repeatability prior to clinical application. METHOD: Sixty healthy older female subjects (aged 72.5 +/- 5 years) participated in this study which involved two tasks. The first was the clinical test: a maximal lateral reach to the right and left, recorded by a clinical measure (observation of hand excursion) and a laboratory measure (3D analysis of hand marker excursion). The second was the recording of centre of pressure (COP) stability limits in the lateral direction by use of a dual force platform system. Eighteen subjects returned for repeatability testing. RESULTS: No significant differences in the measures were found between the sides. Lateral reach as measured by the clinical measure was significantly (p < 0.05) correlated with both the laboratory measure of reach (r = 0.650) and with COP stability limits (r = 0.331). The clinical measure of reach was not significantly different (p > 0.01) from the laboratory measure. High test-retest repeatability (r > 0.94) was found for all measures. CONCLUSIONS: The clinical lateral reach test was found to be an accurate measure of lateral reach ability. As it was significantly correlated with COP excursion it was deemed a valid indicator of lateral stability limits. In addition, the lateral reach test had high test-retest repeatability and was symmetrical between the sides. These promising results support both it's use where a clinical indicator of medio-lateral postural stability is desired and further investigation of the lateral reach test in clinical populations.

Aged↗

Synaptophysin immunoreactivity in primary pigmented nodular adrenocortical disease: neuroendocrine properties of tumors associated with Carney complex.

Carney complex (CNC) is characterized by lentiginosis and myxomatosis together with a variety of endocrine, neural crest-derived, and other tumors, including primary pigmented nodular adrenocortical disease (PPNAD). PPNAD is characterized by lipofuscin-containing, autonomously functioning, cortisol-producing nodules surrounded by mostly atrophic adrenocortical and normal adrenomedullary tissue. The nature and origin of the tumors, including the myxomas and PPNAD, are unclear. In this study, seven paraffin-embedded PPNAD tumors, one skin myxoma, and two cell lines (one myxoma and one PPNAD) established from patients with CNC were stained with antisera for synaptophysin (SYN), neuron-specific enolase, chromogranin A, tyrosine hydroxylase, and the neural cell adhesion molecule (NCAM). In addition, one PPNAD specimen and one myxoma were analyzed by electron microscopy. The results showed that chromogranin A and tyrosine hydroxylase stained adrenomedullary tissue, but not the PPNAD nodules or the extranodular adrenal cortex. SYN, neuron-specific enolase, and NCAM also stained the medulla. PPNAD nodules and the PPNAD cell line, but not the extranodular adrenal cortex, stained intensely for SYN. The myxoma cell line, but not normal fibroblasts, stained for SYN and NCAM. Ultrastructural analysis of a PPNAD tumor and a skin myxoma revealed a well developed rough endoplasmic reticulum, prominent mitochondria, and vesicle-like structures dispersed throughout the cytoplasm. We conclude that immunostaining for SYN, a marker protein for neuroendocrine cells, clearly distinguishes PPNAD nodules from surrounding adrenocortical tissue and can be helpful in the detection of small nodules in apparently unaffected cortex. The cells of a cutaneous myxoma were also stained positive by two of the three neuroendocrine markers. Finally, both PPNAD and myxoma cells demonstrated ultrastructural features suggestive of neuroendocrine properties. These results support the previously suggested hypothesis that the genetic mechanism leading to CNC involves genes with a neuroendocrine role.

Adolescent↗

Small-angle X-ray scattering using coherent undulator radiation at the ESRF.

A simple approach for producing a high-coherent-flux X-ray beam for small-angle-scattering studies used at the Troika beamline of the European Synchrotron Radiation Facility is reported. For such small-angle studies it is permissible to reduce the longitudinal coherence .length of the beam, thus increasing the energy bandpass and intensity of the beam, because there is only a small optical path-length difference. By using mirrors and filters to cut unwanted energies from the undulator harmonic structure, a high-flux beam of >10(9) photons s(-1) through a 5 micron-diameter pinhole at 8.2 keV with a bandpass of 1.3% can be produced. The coherent properties of this beam have been measured by analyzing a static speckle pattern from an aerogel sample imaged by a directly illuminated CCD camera. The speckle size and contrast are compared with the expected values based on a statistical analysis of the intensity distribution of speckle patterns obtained using partially coherent conditions. The expected widths of the spatial autocorrelation are found, but there is an apparent incoherent fraction of the beam which reduces the measured contrast. The method presented is to be used as a tool to optimize conditions for diffraction experiments using coherent X-rays.

Journal Article↗

Effectiveness of a prospective physician self-audit transfusion-monitoring system.

BACKGROUND: The purpose of this study was to search for a more effective transfusion-monitoring system than the existing system of retrospective peer review. STUDY DESIGN AND METHODS: This research used a study-control, preintervention and postintervention design, to evaluate the effectiveness of a prospective physician self-audit transfusion-monitoring system that functioned without the direct involvement of transfusion service physicians. This research also evaluated the effectiveness of issuing to physicians a memo with transfusion guidelines. Three process indicators were used to assess physician behavior at various stages of the blood-ordering process: 1) the number of crossmatches ordered per admission, 2) the transfusion-to-crossmatch ratio, and 3) the number of blood units returned to the laboratory after physician self-auditing. The study used two outcome indicators to reflect overall blood utilization: 1) the percentage of patients who received red cell transfusions and 2) the number of blood units transfused per recipient each month. RESULTS: The prospective physician self-audit system implemented at the study hospital did not reverse physician transfusion decisions, and the process of issuing to physicians a memo with transfusion guidelines at the control hospital failed to reduce blood usage. However, a transient reduction in blood utilization was observed at the study hospital. CONCLUSION: The reduction was hypothesized to be due to a Hawthorne effect, in which observed behavior is affected by the subject's awareness of the research study.

Blood Grouping and Crossmatching↗

Differential regulation of apoptosis in the normal human adrenal gland.

Analysis of apoptosis in the human adrenal appears to be of eminent importance in the understanding of adrenal structure, zonation, and function. In this study we investigated the programmed cell death of normal adrenal tissues on the basis of apoptotic index by the nonradioactive in situ end labeling of DNA fragments, proliferating cell nuclear antigen, (PCNA), CD95 (cluster of differentiation), major histocompatibility complex class II immunohistochemistry, and ultrastructural analysis. The highest apoptotic index was detected in the outermost zones of the adrenal cortex, mainly in the zona glomerulosa. A labeling index of 50.46 +/- 5.22% (mean +/- SEM) for zona glomerulosa, 9.36 +/- 1.68% for zona fasciculata, 3.90 +/- 0.78% for zona reticularis, and 7.37 +/- 1.62% for the zona medullaris was found. Immunohistochemistry was used to distinguish between apoptotic and S phase cells. Positive anti-PCNA staining occurred in the inner cortical zones, whereas anti-CD95 signals appeared throughout the whole cortex, albeit at a much weaker level. MHC class II expression, which is known to be associated with programmed cell death, was demonstrated in the inner cortical zone. The data showed that mechanisms of cell death other than necrosis occur in the adrenal. In conclusion, we found a differential regulation of cell death for each zone of the adrenal cortex; the old theories of adrenal zonation (migrational vs. zonal or transformation theory) may, in fact, correlate with each other.

Adrenal Glands↗

Perfect Crystals in the Asymmetric Bragg Geometry as Optical Elements for Coherent X-ray Beams.

Perfect crystals in the asymmetric Bragg geometry are evaluated as optical elements for manipulating coherent X-ray beams. Such optics can be used to modify the transverse coherence length of a synchrotron X-ray beam, with the intention of increasing the usable coherent flux. The wavelength range, angular divergence and flux of X-rays passing through a pinhole aperture are examined in detail, as functions of source and pinhole size, crystal-to-pinhole separation and the asymmetry factor. In developing this analysis, the behavior of asymmetrically cut crystals is explained in reciprocal space, with reference to the crystal truncation rod associated with the reflection. The results show that, for synchrotron beams that are collimated to a small fraction of the incident Darwin width, the wavelength range accepted by the crystal is typically dispersed into an angular spread in the exit beam. This chromatic aberration greatly reduces the transverse coherence length in a manner that does not conserve the coherent flux. The calculations are in agreement with measurements of the divergence and flux through a micrometer-sized pinhole using a synchrotron wiggler X-ray source.

Journal Article↗

Sensitivity and specificity of five different mycoplasma detection assays.

The sensitivity and specificity of five different mycoplasma detection tests were evaluated in comparison with the classical microbiological culture assay on agar plates as the reference method: direct fluorochrome DNA staining (direct DAPI), DNA staining of an indicator cell line (indirect DAPI), RNA hybridization with a cDNA specific for ribosomal mycoplasmal RNA, an enzyme-linked immunosorbent assay (ELISA) with mycoplasma-specific antibodies, and a biochemical cytotoxicity assay (6-MPDR). A large panel of continuous cell lines (20 adherent and 233 suspension cell lines, most of the latter were human leukemia-lymphoma cell lines) were analyzed for infection with mycoplasma. The results of the comparative analysis for sensitivity and specificity of the various tests were as follows: 100% and 100% for the indirect DAPI, 100% and 98% for the RNA hybridization assay, 87% and 94% for the direct DAPI, 72% and 100% for the ELISA, 75% and 90% for the biochemical 6-MPDR assay. Each of these approaches has both advantages and disadvantages with regard to cost, time, reliability, specificity, and sensitivity. The best compromise for routine mycoplasma testing is a combination of several techniques (e.g. direct culture on agar, RNA hybridization, and direct or indirect DAPI).

Animals↗

Elimination of mycoplasma from infected leukemia cell lines.

The infection of cell lines with mycoplasma can cause severe problems as the contaminants affect virtually every cell parameter. We attempted to eliminate mycoplasma from contaminated cell lines using the fluoroquinolone antibiotic ciprofloxacin. Mycoplasma-infected cell lines were cultured with 10 micrograms/ml ciprofloxacin for 14 days. The elimination or persistence of mycoplasmal infection was monitored by diamidino-2-phenylindole (DAP) DNA staining, RNA hybridization test and broth-agar microbiological culturing. Seventeen out of 21 positive cell lines (81%) have been successfully treated using ciprofloxacin. Mycoplasma infections are unacceptable in experimental in vitro systems and require an elimination procedure of certain efficiency. The use of adequate detection methods in the routine control of cell lines and the avoidance of emerging resistant strains are of the utmost importance.

Cell Line↗