Search PubMed⌕ Search

Biomedical subjects

D Dawson

Publications and source records attributed to D Dawson.

At least 127 records · Page 7Linked to original sources
PubMed1996

Chronobiotics--drugs that shift rhythms.

A chronobiotic is defined and levels of action within the mammalian circadian pacemaker system, such as the retina, retinohypothalamic tract, geniculohypothalamic tract, suprachiasmatic nuclei, output and feedback systems are identified. Classes of drug that include the indoleamines, cholinergic agents, peptides, and benzodiazepines, which might act as chronobiotics within these levels, are evaluated. Particular emphasis is placed on the indole, melatonin (MLT). The clinical circumstances for use of chronobiotics in sleep disturbances of the circadian kind, such as jet lag, shift work, delayed sleep-phase syndrome, advanced sleep-phase syndrome, irregular and non-24-hr sleep-wake cycles, are described under reorganized headings of disorders of entrainment, partial entrainment, and desynchronization. Specific attention is given to the blind and the aged. Both human and animal studies suggest that MLT has powerful chronobiotic properties. MLT shows considerable promise as a prophylactic and therapeutic alternative or supplement to the use of natural and artificial bright light for resetting the circadian pacemaker. Throughout this discussion, the hypnotic and hypothermic versus the chronobiotic actions of MLT are raised. Finally, problems in the design of delivery systems for MLT are discussed.

Chronobiology Phenomena↗
PubMed1996

Genetic characterization of Mycobacterium avium isolates recovered from humans and animals in Australia.

Genetic relationships amongst 115 mainly Australian isolates of Mycobacterium avium were assessed using multilocus enzyme electrophoresis (MEE). The isolates were divided into 58 electrophoretic types (ETs), with a mean genetic diversity of 0.29. Isolates from humans were closely related to but distinct from those cultured from birds, whilst some porcine isolates belonged to the same ETs as certain human isolates. Pulsed field gel electrophoresis (PFGE) was used to differentiate related isolates, and those from birds and some from other animals, including pigs, were distinguished from the human isolates. The results of MEE and PFGE suggested that certain strains of M. avium may be transmitted between birds and pigs, but there was no clear evidence of transmission to humans. The serovar of the M. avium isolates was not obviously related to their ET assignment or their PFGE type.

Animals↗
PubMed1996

Day-time melatonin administration: effects on core temperature and sleep onset latency.

Significant hypothermic and hypnotic effects have been reported for melatonin at a wide range of doses. It has been suggested that this decrease in core temperature (Tc) following melatonin administration may mediate the observed increase in sleepiness. To test this, melatonin was administered to young adults during the day, and the concurrent effects on Tc and sleep onset latency (SOL) were recorded. Sixteen healthy males received either a 5 mg oral formulation of melatonin or placebo at 14.00 hours. Core temperature was recorded continuously. Sleep onset latency to stage 1 (SOL1) and stage 2 (SOL2) were recorded using an hourly multiple sleep latency test (MSLT). Compared with placebo, melatonin significantly decreased Tc 1.5 h after administration for 6 h. Between 15.00 and 18.00 hours, the drop in Tc was associated with a concurrent decrease in SOL1 and SOL2. Following administration mean SOL1 and SOL2 were reduced by 40 and 25%, respectively. In this study, daytime melatonin administration produced a significant decrease in Tc with a corresponding decrease in SOL. Taken together, these data are not inconsistent with the suggestion that melatonin may facilitate sleep onset via a hypothermic effect. In addition, this study provides support for the idea that melatonin may play a role in regulating circadian and/or age-related variations in sleep/wake propensity. From a practical perspective, exogenous melatonin may be useful in the treatment of sleep disorders associated with increased nocturnal Tc.

Adult↗
PubMed1996

Meiotic recombination initiated by a double-strand break in rad50 delta yeast cells otherwise unable to initiate meiotic recombination.

Meiotic recombination in Saccharomyces cerevisiae is initiated by double- strand breaks (DSBs). We have developed a system to compare the properties of meiotic DSBs with those created by the site-specific HO endonuclease. HO endonuclease was expressed under the control of the meiotic-specific SPO13 promoter, creating a DSB at a single site on one of yeast's 16 chromosomes. In Rad+ strains the times of appearance of the HO-induced DSBs and of subsequent recombinants are coincident with those induced by normal meiotic DSBs. Physical monitoring of DNA showed that SPO13: : HO induced gene conversions both in Rad+ and in rad50 delta cells that cannot initiate normal meiotic DSBs. We find that the RAD50 gene is important, but not essential, for recombination even after a DSB has been created in a meiotic cell. In rad50 delta cells, some DSBs are not repaired until a broken chromosome has been packaged into a spore and is subsequently germinated. This suggests that a broken chromosome does not signal an arrest of progression through meiosis. The recombination defect in rad50 delta diploids is not, however, meiotic specific, as mitotic rad50 diploids, experiencing an HO-induced DSB, exhibit similar departures from wild-type recombination.

DNA, Fungal↗
PubMed1996

Consequences of transient focal cerebral ischaemia for second messenger and neurotransmitter binding in the rat: quantitative autoradiographic analysis of forskolin, dopamine D1 receptor binding and cerebral blood flow changes.

In order to study the consequences of reperfusion for ischaemic brain injury, quantitative ligand binding autoradiography was carried out in a model of reversible focal cerebral ischaemia. Endothelin-1 applied to the abluminal surface of the middle cerebral artery in anaesthetized Sprague-Dawley rats induced severe focal ischaemia and subsequent reperfusion (assessed by blood flow tracers [99mTc]HMPAO and [14C]iodoantipyrine respectively) by 2 h after insult. Ligand binding autoradiography on consecutive sections demonstrated these blood flow changes to be associated with a significant reduction in forskolin binding throughout the middle cerebral artery territory (e.g. 25% in parietal cortex, 11% in dorsolateral caudate nucleus). The most marked losses in forskolin binding were in areas where ischaemia was severe and reperfusion was poor. However, the same changes in cerebral blood flow had no significant effect on D1 dopamine receptor binding (e.g. < 2% reduction in the caudate nucleus). These data demonstrate that ligand binding characteristics are significantly affected as early as 2 h after insult, with evidence of differential sensitivity for forskolin and D1 dopamine binding. With regard to the consequences of reperfusion, comparison with our previous study of 2 h maintained ischaemia demonstrates reperfusion-related salvage of dopamine and forskolin binding in the caudate nucleus but possible exacerbation of forskolin binding loss in the cortex.

Animals↗
PubMed1996

The hypothermic effect of melatonin on core body temperature: is more better?

Recent studies have shown that melatonin is both hypnotic and hypothermic at physiological levels. Indeed, the hypnotic effect may be mediated via the hypothermic action. If this is the case, it is important to explore the dose-response relationships for the thermoregulatory effects of melatonin. Four groups of eight healthy adults (n = 32), aged between 18 and 38, each underwent two 12-hr bedrest protocols in which core body temperature (CT) and plasma melatonin levels were measured concurrently between 0800 and 2000 hr. For each group, subjects ingested either sucrose placebo or a 0.1, 0.5, 1.0, or 5.0 mg melatonin capsule at 1600 hr in a double-blind counterbalanced cross-over design. Melatonin was absorbed rapidly, with peak levels being reached after 1 hr at all dose levels. Mean peak plasma melatonin levels increased from physiological to pharmacological levels in a dose-dependent manner. Elimination for all dose levels was rapid, with mean plasma half-lives between 33 and 47 min. At the lower doses the mean drop in CT was between 0.05 and 0.15 degrees C and took between 2 and 3 hr. At the higher doses (1.0 and 5.0 mg), CT fell by 0.25-0.3 degrees C within 30-60 min following ingestion and at the highest dose (5 mg) remained suppressed for the duration of the study. While the magnitude and duration of the drop increased in what appeared to be a dose-dependent manner, it is unlikely that this relationship reflects a simple dose-response curve. There was considerable variability in plasma profiles following administration, particularly at the two lowest doses (0.1 and 0.5 mg). The lower mean drop in CT probably reflects the lower proportion of subjects achieving physiological plasma levels, and therefore a hypothermic effect, at the two lowest doses. If melatonin is to be used to improve sleep onset and maintenance by lowering CT, doses between 1.0 and 5.0 mg appear to be the lowest that produce a consistent drop in CT across all subjects.

Absorption↗
PubMed1996

Multiplex PCR provides a low-cost alternative to DNA probe methods for rapid identification of Mycobacterium avium and Mycobacterium intracellulare.

A multiplex PCR designed to differentiate Mycobacterium tuberculosis complex organisms from M. avium and M. intracellulare was used to test 105 isolates identified by DNA probe methods as M. avium, M. intracellulare, or M. avium complex type X. The multiple PCR correctly identified 33 of 34 isolates identified by commercial probe methods as M. avium and all 51 isolates identified as M. intracellulare. The 20 isolates identified as M. avium complex type X by probe were identified as Mycobacterium spp. by the multiplex method. These results confirm that the multiplex PCR, which is simple to perform and cheaper than commercial probe methods, is suitable for routine identification of M. avium and M. intracellulare.

Costs and Cost Analysis↗
PubMed1996

Urinary 6-sulfatoxymelatonin cycle-to-cycle variability.

For either clinical or research purposes, the timing of the nocturnal onset in production of the urinary melatonin metabolite 6-sulfatoxymelatonin (UaMT6s-onset), has been proposed as a reliable and robust marker of circadian phase. However, given that most circadian rhythms show cycle-to-cycle variability, the statistical reliability of phase estimates obtained from a single study using UaMT6s-onset remains to be determined. Following 2 weeks of sleep diary and wrist actigraphy, 15 young, healthy good sleepers participated in four UaMT6s sampling sessions spaced 1 day apart. During the sampling sessions subjects remained indoors under low light conditions and hourly urine samples were collected from 19:00 to 02:00 h. Samples were subsequently assayed for UaMT6s using standard radioimmunographic techniques. UaMT6s-onset was determined by the time at which melatonin production exceeded the average of three proceeding trials by 100%. Sleep onset times were derived from sleep diary and actigraphic measures taken before the melatonin collection nights. We found that there was no significant variation between nights in group mean UaMT6s-onset times, and intraindividual variability was small. In addition, UaMT6s-onset times were highly and significantly correlated between nights (grand mean r = 0.804). Our results suggest that within 95% confidence interval limits, individual UaMT6s-onset estimates obtained from a single night UaMT6s-onset study can be used to predict subsequent UaMT6s-onset times within +/- 97 min. A close temporal relationship was also found between the timing of UaMT6s-onset and sleep onset. Overall, our results suggest that under entrained conditions single-session UaMT6s-onset studies can provide reliable individual UaMT6s-onset phase estimates and that the protocol described in this study is a practical and noninvasive methodology.

Adolescent↗
PubMed1996

Gymnasts, distance runners, anorexics body composition and menstrual status.

Ten top class female distance runners, ten female anorexics and twenty female gymnasts of a similar age were compared for height, mass, %fat, fat mass, lean body mass, age of menarche and incidence of amenorrhoea. The mean age of the distance runners, anorexics, and gymnasts was 13.6 years, 14.7 years, and 13.3 years respectively. In comparison to normal data on females of a similar age they were shorter, lighter, had lower fat masses, and %fat, and the gymnasts and anorexics had lower lean body masses. However, the gymnasts and runners had higher lean body masses compared with the anorexic group. There were no significant differences in body composition by hydrostatic weighing but of these three groups the anorexics tended to have the highest total skinfold, %fat and fat masses. Only 20% of the gymnasts, 40% of the runners and 70% of the anorexics had started menstruating compared with 95% of girls of a similar age. Of the girls in our study who had started menstruating one gymnast, (25% of sub-group) two runners (50% of sub-group) and seven anorexics (100% of sub-group) had developed secondary amenorrhoea. The low body masses, low fat masses, delayed menarche and secondary amenorrhoea in athletes are discussed in relation to low caloric intake, stress, hormone levels, high training loads and genetic factors. Our data demonstrating no significant differences in body composition variables between the three groups of young girls, support the main contention that this type of physique may arise through different mechanisms leading to a common outcome, but without a proven causal link between anorexia and athletic performance.

Adolescent↗
PubMed1996

Office carpal tunnel release with wrist block and wrist tourniquet.

Carpal tunnel release is usually performed in a hospital setting with regional anesthesia. The cost for use of the hospital operating room, anesthesia, and surgeon's fee is quite excessive. Over the past 5 years we have performed carpal tunnel releases in the office setting using wrist block anesthesia and a wrist tourniquet. There have been no complications, and the 20 patients interviewed and examined for this article preferred the office procedure over the hospital procedure. Carpal tunnel release can be performed safely in the office, and is less expensive than when done in a hospital setting.

Ambulatory Surgical Procedures↗
PubMed1996

Assays for microbial contamination and DNA analysis based on electrorotation.

A new assay is described for determining the concentration and viability of waterborne micro-organisms. The method exploits the fact that when a latex bead coated with a specific binding agent is complexed to the target analyte, the analyte complex formed assumes new dielectric properties that can be monitored by its electrorotation response. This generic technology is applicable to a wide range of organism and toxicological diagnostic tests, as well as to other areas of biotechnology. An example is given of its possible application to DNA sequence analysis.

Animals↗
PubMed1996

Gender differences in the risk of alcohol dependence: United States, 1992.

Data from a representative sample of US adults revealed that 24% of male life-time drinkers and 15% of female life-time drinkers met the DSM-IV criteria for life-time alcohol dependence, i.e. dependence during the year preceding interview or in any 12-month period prior to that year. The median interval from first drink to onset of dependence was 3.6 years for men and 3.0 years for women. After using survival techniques to adjust for potential gender differences in the exposure to risk of developing alcohol dependence, the cumulative conditional probability of having experienced onset of dependence was 35.1% for men and 24.6% for women. The conditional probability of onset of dependence was equal for men and women in the first year after initiation of drinking, about 30% higher for men in the period 1-4 years after the first drink, and about 45% higher for men thereafter. After using proportional hazards models to adjust for the effects of age cohort, race and ethnicity, family history of alcoholism and age at first drink, these period-specific risk ratios remained virtually unchanged. Including a measure of average daily ethanol intake during periods of heaviest consumption rendered most of the gender differences statistically insignificant, revealing a slight excess risk of female dependence within the first year after initiation of drinking among the heaviest drinkers and leaving an excess male risk of dependence mostly among individuals with average daily intakes of less than one ounce of ethanol. The results suggest that different frequencies of binge drinking might help to account for these remaining gender differences and that men's and women's relative risks of developing alcohol dependence may vary as a function of life cycle stage, with men's excess risk greatest in the college/young adult years.

Adolescent↗
PubMed1995

The effects of a ring chromosome on the meiotic segregation of other chromosomes in Saccharomyces cerevisiae.

Meiotic chromosome segregation must occur with high fidelity in order to prevent the generation of aneuploid cells. We have previously described the identification and genetic characterization of a yeast mutant with defects in meiotic sister-chromatid segregation. We attributed the phenotype in this mutant to a dominant allele, which we referred to as SID1-1. These mutants appeared to exhibit high levels of non-disjunction and precocious separation of sister-chromatids of chromosome III, as well as precocious separation of sister chromatids of chromosome VIII and a univalent artificial chromosome. We show here that the unusual meiotic behavior of chromosome III in these strains is due to the presence of a ring III chromosome, rather than a mutant gene. Additional experiments demonstrate that a ring III/rod III pair alters the meiotic segregation of a univalent artificial chromosome.

Chromosomes, Artificial, Yeast↗
PubMed1995

Tau protein is altered by focal cerebral ischaemia in the rat: an immunohistochemical and immunoblotting study.

Breakdown of the cytoskeleton may be involved in the evolution of ischaemic brain damage and alterations in microtubule-associated proteins may play an important role in this process. In the present study, tau, a microtubule-associated protein predominantly located in axons, was examined after 2 or 6 h of focal cerebral ischaemia in the rat. Immunohistochemistry revealed increased Tau1 staining in the neuropil, some perikarya and in glial cells throughout the dorsolateral caudate nucleus and ventrolateral neocortex in the ipsilateral hemisphere at both 2 and 6 h after occlusion of the middle cerebral artery. Contrastingly, immunostaining of another tau antibody, TP70, was unchanged in the neuropil, but was increased specifically in glial cells in these regions. Immunoblotting revealed the presence of additional tau bands in tissue extracts of the caudate nucleus and ventrolateral neocortex ipsilateral to the occluded middle cerebral artery as detected by both tau antibodies after either 2 or 6 h. The results suggest that tau is dephosphorylated and/or degraded in axons and some neuronal perikarya in response to focal cerebral ischaemia. In contrast to the response in neurons, increased immunoreactivity of both tau antibodies in glial cells indicates a differential response of neuronal and glial tau to focal cerebral ischaemia.

Animals↗
PubMed1995

Association between left ventricular hypertrophy and erythrocyte sodium-lithium exchange in normotensive subjects with and without NIDDM.

The determinants of left ventricular mass in normal control subjects and subjects with non-insulin-dependent diabetes (NIDDM) are ill-defined. We therefore recorded M-mode and pulsed Doppler echocardiograms and 24-h ambulatory blood pressure in 57 normotensive subjects, 34 with NIDDM and 23 matched non-diabetic control subjects. Measurements of erythrocyte sodium-lithium counter-transport, plasma angiotensin II, plasma and platelet catecholamines and fasting plasma insulin were also made. Six control subjects (26%) and 15 diabetic subjects (44%) had some degree of left ventricular hypertrophy. Subjects with left ventricular hypertrophy (n = 21) had an elevated mean rate of sodium-lithium countertransport (0.40 +/- 0.13 vs 0.31 +/- 0.09 mmol.l-1.h-1; p < 0.01), parallel differences being observed in both the diabetic and control groups. Twelve of the subjects with left ventricular hypertrophy (57%) had elevated rates of sodium-lithium counter-transport compared to only seven (19%) of those without (p < 0.05). There was no consistent difference between those with and without left ventricular hypertrophy in any other clinical or biochemical variable. Multivariate analysis, with the presence or absence of left ventricular hypertrophy as the dependent variable, demonstrated that the maximal rate of sodium-lithium countertransport was the only variable that independently contributed to left ventricular hypertrophy (partial r = 0.35; F1.55 = 7.74; p = 0.007). This study demonstrates for the first time an association between left ventricular hypertrophy and erythrocyte membrane cation transport that is independent of hypertension, is present in both diabetic and non-diabetic groups, and may represent a link between elevated rates of membrane sodium transport and cardiovascular risk.

Adult↗
PubMed1995

Uniform prehospital data elements and definitions: a report from the uniform prehospital emergency medical services data conference.

One of the district and universal aspects of emergency medical service (EMS) is the belief that before its implementation many people were dying or being killed by ill-equipped, poorly trained "hearse drivers" and that this tragic state of affairs has been rectified by the advances in the prehospital phase of care. Except for cases of nontraumatic, out-of-hospital cardiac arrest there is almost no convincing scientific evidence to prove that prehospital care has had an impact on morbidity or mortality. At the very foundation of this problem is the lack of a set of broad-based, well-conceived, accurate, reliable, uniform EMS data. Many attempts have been made to develop a uniform EMS data set, but without a national consensus these have not achieved wide distribution. In 1992, with the assistance of the National Highway Traffic Safety Administration, the national consensus process began with a series of meetings involving many EMS agencies and organizations. This culminated in August 1994 with the development of an 81-item uniform EMS data set. We detail the prior attempts at data set development and outline the process leading to the this uniform, national EMS data set.

Data Collection↗
PubMed1995

Improving adaptation to simulated night shift: timed exposure to bright light versus daytime melatonin administration.

Chronic circadian disturbance is thought to cause many of the health and social problems reported by shift workers. In recent years, appropriately timed exposure to bright light and exogenous melatonin have been used to accelerate adaptation to phase shifts of the circadian system. In this study we compared adaptation to night shift in three groups of subjects. The first treatment group received timed exposure to bright light (4-7,000 lux between 2400 and 0400 hours on each of three night shifts). The second treatment group received exogenous melatonin by capsule (2 mg at 0800 hours then 1 mg at 1100 and 1400 hours). The placebo control groups received either dim red light at less than 50 lux or placebo (sucrose) in identical capsules at the same time. Results indicated that all groups shifted significantly from baseline. Using the dim-light melatonin onset as a circadian marker, the bright-light group shifted the furthest, whereas there was no significant difference between the melatonin and placebo groups. Sleep quality as determined by wrist actigraphy was most improved in the light-treatment group, although the melatonin group also showed significant improvements. Cognitive psychomotor performance was most improved in the light-treatment group and the melatonin group again showed little difference from the control group. Although melatonin was unable to increase the amount of the phase shift following transition to night shift, it is likely that the intermediate levels of improvement in sleep reflect the hypothermic effects of melatonin. By lowering core temperature across the sleep period, sleep may be enhanced. This improvement in sleep quality did not produce concomitant improvements in shift performance for the melatonin group. This suggests that the enhanced performance in the light-treatment group may reflect more direct "energizing" effects. On the basis of these results, bright light is clearly superior in its ability ot phase shift the circadian system and thereby improve sleep and performance. However, melatonin may permit shift workers to override the circadian system for short periods and avoid the potential toxicity due to overzealous manipulations of the circadian pacemaker. In rapidly rotating shift schedules, melatonin may be preferable because it would not require workers to reverse the large phase shift induced by light.

Adolescent↗