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Biomedical subjects

C Downing

Publications and source records attributed to C Downing.

11 recordsLinked to original sources

Genetic analysis of the psychomotor stimulant effect of ethanol.

Genetic influences on the psychomotor stimulant effect of ethanol may be a key feature of abuse liability. While earlier work has shown the activational effects of ethanol to be under the influence of a relatively uncomplicated additive genetic system, preliminary data from our laboratory suggested the possibility of nonadditive genetic variance. In the present study, a full Mendelian cross was conducted to further characterize gene action and search for quantitative trait loci (QTL) influencing the psychomotor stimulant properties of ethanol. We tested 3062 mice of the six Mendelian cross genotypes (P1, P2, F1, F2, BC1 and BC2) derived from a cross between the C57BL/6J (B6) and C3H/HeJ (C3H) inbred strains of mice. On day 1, mice were injected with saline, put in a holding cage for 5 min, then placed in an activity monitor for 5 min. On day 2, mice were injected with 1.5 g/kg ethanol, and activity again monitored for 5 min. Analysis showed the expected activation in the C3H strain and little activation in the B6 strain, with no effect of sex. Biometrical genetic analysis showed a best-fit model that included the mean (m), additive effect (a), and an epistatic parameter (i = homozygote by homozygote interaction). Analysis showed good evidence for QTL on chromosomes 1 (logarithm of odds (LOD) 3.4-7.5, 88-100 cM), 6 (LOD 9.1-10.4, 46-50 cM) and 15 (LOD 7.3-8.8, 28-32 cM). While the regions on chromosomes 1 and 6 have previously been implicated in several different ethanol-related phenotypes, this is the first report of a QTL influencing the psychomotor stimulant properties of ethanol on chromosome 15. Other studies have identified QTL in this region of chromosome 15 mediating locomotor activation caused by other psychostimulants, including cocaine, amphetamine and phencyclidine.

Animals↗

Epigenetic randomness, complexity and singularity of human iris patterns.

We investigated the randomness and uniqueness of human iris patterns by mathematically comparing 2.3 million different pairs of eye images. The phase structure of each iris pattern was extracted by demodulation with quadrature wavelets spanning several scales of analysis. The resulting distribution of phase sequence variation among different eyes was precisely binomial, revealing 244 independent degrees of freedom. This amount of statistical variability corresponds to an entropy (information density) of about 3.2 bits mm(-2) over the iris. It implies that the probability of two different irides agreeing by chance in more than 70% of their phase sequence is about one in 7 billion. We also compared images of genetically identical irides, from the left and right eyes of 324 persons, and from monozygotic twins. Their relative phase sequence variation generated the same statistical distribution as did unrelated eyes. This indicates that apart from overall form and colour, iris patterns are determined epigenetically by random events in the morphogenesis of this tissue. The resulting diversity, and the combinatorial complexity created by so many dimensions of random variation, mean that the failure of a simple test of statistical independence performed on iris patterns can serve as a reliable rapid basis for automatic personal identification.

Functional Laterality↗

A biologically motivated solution to the cocktail party problem.

We present a new approach to the cocktail party problem that uses a cortronic artificial neural network architecture (Hecht-Nielsen, 1998) as the front end of a speech processing system. Our approach is novel in three important respects. First, our method assumes and exploits detailed knowledge of the signals we wish to attend to in the cocktail party environment. Second, our goal is to provide preprocessing in advance of a pattern recognition system rather than to separate one or more of the mixed sources explicitly. Third, the neural network model we employ is more biologically feasible than are most other approaches to the cocktail party problem. Although the focus here is on the cocktail party problem, the method presented in this study can be applied to other areas of information processing.

Artificial Intelligence↗

Cytoplasmic factors do not contribute to a maternal effect on ethanol teratogenesis.

Both maternal and fetal genetic factors influence variations in response to prenatal ethanol exposure. To assess the effect of maternal genotype on the incidence of ethanol teratogenesis, a reciprocal cross study was conducted in an animal mode using the relatively susceptible C57BL/6J (B6) and the relatively resistant DBA/2J (D2) inbred mice. This mating pattern produced four embryonic genotypes: true-bred B6B6 and D2D2 litters and hybrid B6D2 and D2B6 litters. To examine the role of maternal egg cytoplasm as the source of variation that could account for a maternal effect, B6D2 and D2B6 F1 females were mated back to B6 males, which produced two additional embryonic genotypes: B6D2.B6 and D2B6.B6. Dams were intubated with either 5.8 g/kg of ethanol or an isocaloric amount of maltose-dextrin on day 9 of pregnancy. On day 18 of pregnancy, dams were sacrificed, fetuses were removed, weighed, sexed, and examined for gross morphological malformations. Every other fetus within a litter was prepared for either skeletal or soft tissue analysis. Results showed a higher rate of teratogenesis in the B6D2 group compared to the genetically similar D2B6 group, which indicates an influence of maternal genotype on susceptibility to ethanol teratogenesis. The percentage of affected male and female fetuses did not differ, which suggests that sex-linked factors are not responsible for the maternal effect. The backcross B6D2.B6 and D2B6.B6 litters did not differ significantly for any measure of teratogenesis, suggesting that differences in maternally transmitted cytoplasmic material are not the cause of the maternal effect. Factors that could account for the maternal effect are differences in the maternal uterine environment and genomic imprinting. Separating maternal from fetal-mediated mechanisms responsible for susceptibility to ethanol teratogenesis is needed for identifying mothers and infants at risk.

Abnormalities, Drug-Induced↗

Endogenous plasma atrial natriuretic peptide and the control of salt gland function in the Pekin duck.

Polyclonal antibodies raised in a rabbit against avian atrial natriuretic peptide (ANP) were used to investigate the role of endogenous plasma ANP in the control of salt gland function of conscious, saltwater-adapted Pekin ducks. Salt gland secretion was initiated and maintained either by a hypervolemic (290 mosmol/kg NaCl i.v. at 2 ml/min) or hyperosmotic (1,000 mosmol/kg NaCl i.v. at 0.4 ml/min) stimulus. Both experimental conditions caused significant elevations in endogenous plasma ANP concentrations. At steady states of secretion driven by hypervolemia, the administration of ANP antiserum (anti-ANP), which reduced plasma ANP concentrations by 90%, caused an immediate 30% reduction in fluid secretion rate and sodium excretion that lasted for 20-30 min. The activity of salt glands driven by hyperosmolality was not changed by anti-ANP. The results show that the high circulating concentrations of endogenous ANP associated with conditions of sustained volume expansion promote salt gland secretion.

Acclimatization↗

Total vitamin C, ascorbic acid, and dehydroascorbic acid concentrations in plasma of critically ill patients.

Plasma concentrations of the antioxidant vitamin ascorbic acid were measured by high-performance liquid chromatography in critically ill patients in whom the excessive generation of reactive oxygen species could compromise antioxidant defense mechanisms. Median concentrations of both total vitamin C (ascorbic acid and dehydroascorbic acid) and ascorbic acid in these patients were < 25% (P < 0.001) of the values found in healthy control subjects and in subjects in two other disease groups (diabetes, gastritis) in which reactive oxygen species are reported to be increased. The low values could not be explained by age, sex, intake, or treatment differences, but were associated with the severity of the illness and were not prevented by the use of parenteral nutrition containing ascorbic acid. In addition, the vitamin was less stable in blood samples taken from critically ill patients than in similar samples from subjects in the other groups. The findings indicate that antioxidant defenses could be considerably compromised in these very sick patients. If this reduces the patient's capacity to scavenge reactive species, then the potential of these species to damage DNA and lipid membranes could be increased and compromise recovery.

Adult↗

Pulse oximetry during helicopter transport.

The study objective was to determine if pulse oximetry readings obtained during helicopter transport were indicative of subsequent arterial blood-gas measured saturations. A prospective study design was chosen. Data were gathered on a convenience sample of patients 18 years and older not under cardiopulmonary resuscitation; 101 patients were used for the study. Pulse oximeter readings of oxygen saturation and heart rate were recorded along with simultaneous vital signs. Arterial saturation in blood gases drawn in the emergency department were added to the patient record. Improper functioning of the pulse oximeter was recorded on 10 (9.9%) of the patients. No correlation was found between the probe type and the documented problems (PHI = 0.009). The pulse oximeter saturation readings were not significantly different from arterial saturation in blood gases when compared by paired samples t-test (t = 0.880, p = 0.383). There was also no significant difference between the patient's heart rate sensed by the pulse oximeter and the simultaneous palpated pulse rate. Percent saturation readings by repeated measures were statistically different (p < 0.05) showing a minimal improvement in saturation over time. Based on this study's findings, the authors feel the pulse oximeter can be a valuable adjunct to patient care during helicopter transport.

Aircraft↗

Preparation and characterization of diaspirin cross-linked hemoglobin solutions for preclinical studies.

During 1990 and 1991 the capability for repetitive, consecutive production of DCLHb solution to meet a rigorous and complete set of product criteria was demonstrated. In addition, through periodic monitoring of product stored under controlled conditions, the stability of all lots of DCLHb solution during frozen storage was demonstrated for more than a year. In this way, assurance was provided that the DCLHb solution used in preclinical testing met all product criteria throughout the biological testing period.

Aspirin↗

Helicopter loading time study: hot versus cold.

INTRODUCTION: Historically our program has used the practice of hot-loading at scenes as a time-saving measure. This practice potentially exposes patients and health care personnel to a variety of risks. Currently no data exist supporting the use of hot-loading as a time-saving technique. We prospectively studied load times and scene times for both hot- and cold-loading methods. METHODS: Hot- or cold-loading methods were randomized according to odd or even days of the month for scene runs. Both loading times and total scene times were recorded. An ANOVA was used to compare the times, taking into consideration the aircraft in use (BO 105 or BK 117). RESULTS: A total of 104 flights were entered into the study. For loading time, hot-loading showed a statistically significant difference (F [1,100] = 112.84, P = 0.000). Means for hot- and cold-loading times are 3.071 and 5.033 minutes, respectively. The interaction effect of aircraft and loading method also was significant (F [1,100] = 4.637, P = 0.034). The BO 105 (on high skids) was slower to hot-load. In contrast, the BK 117 (additional pretakeoff system checks) was slower to cold-load. The type of aircraft alone showed no effect on loading time. Total scene times were evaluated using the same procedures. A statistically significant difference also was found for the effect of hot-loading on total scene time (F [1,100] = 11.391, P = 0.001). Means for hot and cold total scene times are 10.54 and 13.615 minutes, respectively. CONCLUSION: Hot-loading does decrease our program's overall scene times. The clinical significance of this procedure was not evaluated.

Air Ambulances↗