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Biomedical subjects

D Dawson

Publications and source records attributed to D Dawson.

At least 109 records · Page 6Linked to original sources
PubMed1998

Integrating the actions of melatonin on human physiology.

Melatonin has a diverse range of physiological effects in humans. Reported effects include modulation of the sleep-wake, thermoregulatory, cognitive, cardiovascular and immune systems. While integrating these broad-ranging effects is difficult when current paradigms are used, the diverse effects of melatonin on human physiology may be better understood by shifting our theoretical perspective. Traditionally, research has treated melatonin as a classical hormone for which a defined effect in physiological systems and a mechanism of action can be elucidated. In this article, we suggest that it may be more appropriate to view melatonin as an evolutionally stable timing signal to which each species has adapted the timing of physiological processes. From this perspective, it appears that the physiological role of melatonin in humans falls into two categories. The first relates to the self-regulation of circadian timing by the suprachiasmatic nucleus-pineal complex. The second relates to the promotion of restorative or anabolic physiological processes. In humans, elevated melatonin levels have been associated with reduced core temperature, increased heat loss, decreased cardiovascular output, reduced alertness and enhanced immune responsiveness. Taken together, these changes suggest that melatonin may increase the propensity for physiological processes promoting nocturnal sleep or processes that occur during the sleep period.

Body Temperature Regulation↗
PubMed1998

Meta-analysis of antiretroviral effects on HIV-1 RNA, CD4 cell count and progression to AIDS or death.

There is uncertainty as to how the effects of antiretroviral treatments on human immunodeficiency virus type 1 (HIV-1) RNA levels and CD4 cell counts can predict reductions in clinical progression to AIDS or death. A meta-analysis was conducted for 27 pairwise comparisons of antiretroviral treatments in 15 randomized trials of antiretroviral treatments. For each trial, three measures of treatment effect were used: (i) 16 week change from baseline in HIV-1 RNA; (ii) 16 week change from baseline in CD4 cell count; and (iii) rate of clinical progression. Treatments which caused greater increases in CD4 cell count and greater reductions in HIV-1 RNA were more effective at reducing the rate of clinical progression (P < 0.05 for each comparison). However, there was variability in the consistency of this correlation between different trials and treatments. The results support the use of both CD4 count and HIV-1 RNA levels as the primary markers of the efficacy of antiretroviral treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Prediction of HIV-1 RNA suppression and its durability during treatment with zidovudine/lamivudine.

To predict the probability of long-term viral suppression during treatment with zidovudine and lamivudine, human immunodeficiency virus type 1 (HIV-1) RNA values were retrospectively pooled for 1083 patients from six randomized, double-blind clinical trials. All analyses of HIV-1 RNA were obtained using the Roche Amplicor assay or its earlier prototype. Time to loss of response was evaluated by Kaplan-Meier analysis; Cox proportional hazards models were used to assess the influence of baseline variables. Among 523 patients with < or = 6 months of prior zidovudine treatment, the probability of HIV-1 RNA suppression below 400 copies/ml at 48 weeks was 71% in those with baseline HIV-1 RNA < 5000 copies/ml, but only 14% in those with HIV-1 RNA between 50,000 and 200,000 copies/ml. Among 560 patients with > 6 months of prior zidovudine treatment, the rates of sustained viral suppression were lower, but also significantly associated with the baseline HIV-1 RNA. Multivariate analyses showed no independent effect of CD4 cell count, age, sex, race, or CDC disease stage on the probability of sustained HIV-1 RNA suppression. When patients with < or = 6 months of prior therapy were stratified based on the magnitude of HIV-1 RNA nadir achieved during treatment, those who reached a nadir of < 400 copies/ml retained this response for significantly longer time periods than the ones who only achieved partial viral suppression. In conclusion, baseline HIV-1 RNA levels and the duration of prior zidovudine therapy strongly predict the antiretroviral efficacy of zidovudine/lamivudine. The baseline parameters should influence the choice of the antiretroviral regimen.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance, 1994 and 1995. Report of the Australian Mycobacterium Reference Laboratory Network.

The Australian Mycobacterium Reference Laboratory Network collected and analysed laboratory data on isolates of Mycobacterium tuberculosis reported during 1994 and 1995. The total number of confirmed isolates was 708 in 1994 and 705 in 1995. This represents an annual incidence of approximately 4 cases of laboratory confirmed tuberculosis per 100,000 population. These figures are similar to those reported in previous years and confirms that the incidence of tuberculosis in Australia remains stable. The incidence rate varied between States. Overall the male:female ratio fell, and there were signs of a downward shift in the median age. We were unable to assess the impact of HIV infection on the number of isolates reported. Positive microscopy was obtained in 55-60% of patients with pulmonary disease. Approximately 8% of isolates had in vitro resistance to at least one of the four standard anti-tuberculosis drugs. Over the two year period seven strains were found to be multi-drug resistant. Overall, the data from 1994-1995 gives no indication of a significant change in the drug susceptibility profiles of isolates from Australian patients with tuberculosis.

Adolescent↗
PubMed1997

Sleep disruption and mood changes associated with menopause.

This study examined the sleep and mood differences between premenopausal and perimenopausal women matched for age and sociodemographic variables. Wrist actigraphy, Profile of Mood State (POMS), State-Trait Anxiety Inventory (STAI), a sleep questionnaire, and responses to a sleep diary were recorded for a period of 1 week. It was found that the sleep disruption of perimenopausal subjects was significantly greater than that of the premenopausal group (p < 0.05). Overall, the perimenopausal group demonstrated a significant increase in sleep disruption and mood alterations when compared with the premenopausal group. Actigraphic data showed that perimenopausal subjects experienced longer and more numerous arousals resulting in significantly less sleep (p < 0.05). In addition, perimenopausal subjects scored significantly higher (p < 0.05) on the STAI and significantly lower on the Vigor subscale of the POMS (p < 0.01) than premenopausal subjects. Correlational analyses indicated that sleep and mood changes were significantly related in the perimenopausal group, but not in the premenopausal group. Taken together, these results suggest that the mood changes experienced by the perimenopausal group may be mediated by sleep disruption.

Adult↗
PubMed1997

Effect of atenolol on nocturnal sleep and temperature in young men: reversal by pharmacological doses of melatonin.

To examine the physiological role of melatonin in sleep, nocturnal melatonin secretion was suppressed using 100 mg oral atenolol in two studies. In Study 1, nocturnal sleep was recorded in 8 young men over 4 nights. Subjects received atenolol on one of the last 2 nights and showed significantly increased total wake time (TWT) and wakefulness after sleep onset (WASO), as well as decreased REM sleep and slow-wave sleep (SWS). When melatonin (total 5 mg) was given after atenolol on the other night, the changes in TWT, WASO, REM, and SWS were reversed. In Study 2, sleep onset latencies (SOL) and core temperature (Tc) of 10 young men were measured for 3 nonconsecutive nights. In a cross-over design, atenolol given on one night significantly suppressed urinary 6-sulphatoxymelatonin (6s-aMT) production and increased hourly measures of Tc and SOL relative to baseline night values. Oral melatonin (3 mg), administered after atenolol, reversed the changes in Tc and SOL. These results suggest that endogenous melatonin may assist in the maintenance of normal sleep architecture (Study 1) and also increase nocturnal sleep propensity by hypothermic effects (Study 2).

Adult↗
PubMed1997

Daytime melatonin administration in elderly good and poor sleepers: effects on core body temperature and sleep latency.

Melatonin has been shown to have hypnotic and hypothermic effects in young adults and has been proposed as treatment for insomnia. However, the hypnotic and thermoregulatory effects of melatonin remain to be simultaneously investigated for aged good and poor sleepers. The aim of this study was to explore the short-term effects of exogenous oral daytime melatonin on core body temperature, sleep latency, and subjective vigor and affect in aged women. Twelve sleep maintenance insomniacs and 10 good sleeping postmenopausal female subjects [mean (SD) age = 65.2 (7.4) years] participated in a double-blind, crossover study in which they received a capsule containing either melatonin (5 mg) or a placebo at 1400 hours. Continuous core body temperature and hourly multiple sleep latency tests (MSLT) were collected from 1100-2030 hours. Self-reported estimates of global vigor (sleepiness) and affect were collected prior to each MSLT using visual analog scales. Comparison of good and poor sleepers failed to reveal any significant differences in core body temperature, sleep latency, or subjective vigor and affect. However, for both groups combined, melatonin administration [absolute postadministration mean (SEM) = 36.9 (0.05) degrees C] significantly lowered core body temperature compared with placebo [37.1 (0.05) degrees C]. Similarly, melatonin administration significantly reduced latency to stage 1 (SOL1) and stage 2 (SOL2) [absolute postadministration mean SOL1 = 20.1 (1.7) and SOL2 = 20.7 (1.6) minutes] compared with placebo [SOL1 = 24.3 (1.2) and SOL2 = 25.2 (1.1) minutes]. Treatment had no significant effect on either vigor or affect. Overall, our results suggest that although short-term exogenous oral daytime melatonin has significant hypothermic and hypnotic effects in aged women, the size of the effects is modest.

Aged↗
PubMed1997

Similar serovar and drug susceptibility profiles among AIDS-related Mycobacterium avium isolates from diverse geographic locations.

Serotyping was performed on Mycobacterium avium isolates from 40 AIDS patients from 5 geographic sites: Boston (17 patients), New Hampshire (4 patients), Finland (12 patients), Trinidad (3 patients), and Kenya (4 patients). Serovars were similar from the five sites. Serovars 4 and 8 were the most common. In addition, minimal inhibitory concentrations to 8 antimicrobial agents were determined for 31 of these isolates and for 21 additional patient isolates from these sites. Minimal inhibitory concentration90 values for clarithromycin, azithromycin, clofazimine, amikacin, ethambutol, ciprofloxacin, sparfloxacin, and rifabutin were similar for isolates from the five geographic sites. Antimicrobial susceptibility patterns did not differ by serovar.

AIDS-Related Opportunistic Infections↗
PubMed1997

Effect of melatonin and corticosteroid on in vitro cellular immune function in humans.

It is well accepted that the immune system shows circadian rhythmicity and that circadian disruption can significantly alter indices of immune function. Recently, a functional link between the endocrine and immune systems has been proposed to explain circadian rhythms in immune activity. Of particular interest is the finding that hormones such as melatonin and corticosteroid are able to exert modulating effects on lymphocyte proliferation. Previous research examining the effects of melatonin in vitro, however, has produced equivocal results. The aim of this study, therefore, was to examine the effects of melatonin and corticosteroid, both separately and together, on mitogen-stimulated human lymphocyte proliferation. Purified human lymphocytes were stimulated with concanavalin A (Con A, 4 micrograms/mL). Melatonin and/or corticosteroid were added to the culture medium during incubation. All cultures were done in quadruplicate. As expected, corticosteroid (25-1,000 ng/mL) significantly reduced proliferation by between 30 and 60% in a dose-related manner (P < 0.0001). Melatonin alone (10-1,000 fmol/mL) did not significantly affect lymphocyte proliferation. However, when lymphocytes were cultured in the presence of melatonin and corticosteroid, a significant decrease in proliferative function of 50-85% was observed (P < 0.0001). Hence, the effect of melatonin and corticosteroid combined was significantly greater than that observed with corticosteroid alone (P < 0.0001). Therefore, it appears that the in vitro effect of corticosteroid on immune function may be modulated by melatonin in physiological to pharmacological concentrations.

Adjuvants, Immunologic↗
PubMed1997

Salivary melatonin as a circadian phase marker: validation and comparison to plasma melatonin.

There are many situations in which it would be useful to know the phase state of the biological clock. It is recognized that measurement of melatonin levels can provide this information, but traditionally blood has been used for the analysis, and there are many problems in extending the measurements into the home or field situations. The aim of this study was to develop and validate a salivary melatonin radioimmunoassay and to compare results obtained against a plasma assay for determining the onset of melatonin secretion. The assay developed was sensitive (4.3 pM) and required only 200 microliters of sample. A rhythm in melatonin was detected in saliva, peaking at approximately 120 pM or 30% of the plasma levels. Using an objective criterion for determining the onset of secretion (mean +/- 2 standard deviations of three daytime samples), the time of onset was shown to exhibit low intraindividual variability (coefficient of variation = 1.5%-4.3%). The time of onset determined using saliva was significantly correlated with the plasma onset (r = .70, p < .05). The onsets determined were 22:30 h +/- 22 min for the saliva and 21:50 h +/- 16 min for plasma for 17 subjects. Similarly, the acrophases of the saliva and plasma melatonin rhythms were significantly correlated. Neither posture alone nor changes in posture affected the calculation of the onset of melatonin secretion using the saliva approach. Very high saliva flow rates induced by citric acid resulted in lower melatonin concentrations compared to the gentle chewing on parafin film. These results firmly establish the use of salivary melatonin measurements for phase typing of the melatonin rhythm in humans.

Adult↗
PubMed1996

Exchanges are not equally able to enhance meiotic chromosome segregation in yeast.

Homologous chromosomes pair, and then migrate to opposite poles of the spindle at meiosis I. In most eukaryotic organisms, reciprocal recombinations (crossovers) between the homologs are critical to the success of this process. Individuals with defects in meiotic recombination typically produce high levels of aneuploid gametes and exhibit low fertility or are sterile. The experiments described here were designed to test whether different crossovers are equally able to contribute to the fidelity of meiotic chromosome segregation in yeast. These experiments were performed with model chromosomes with which it was possible to control and measure the distributions of meiotic crossovers in wild-type cells. Physical and genetic approaches were used to map crossover positions on model chromosomes and to correlate crossover position with meiotic segregation behavior. The results show that crossovers at different chromosomal positions have different abilities to enhance the fidelity of meiotic segregation.

Chromosome Mapping↗
PubMed1996

Topographic profile of reperfusion into MCA territory following endothelin-1-induced transient focal cerebral ischaemia.

This study examines the topographic profile of reperfusion into ischaemic tissue following reversible middle cerebral artery (MCA) occlusion. Autoradiographic images of both ischaemia and reperfusion were prepared from brain sections following transient ischaemia induced by endothelin-1 application to the exposed MCA in anaesthetised rats. Blood flow changes were assessed using double tracer autoradiography with 99mTc-exametazime during ischaemia (5 min) and 14C-iodoantipyrine during reperfusion (2 h). Following a significant ischaemic insult, reperfusion was relatively homogeneous within MCA territory but incomplete at 2 h. There was evidence for differential reperfusion in the cortex and caudate nucleus, and increased collateral supply from the anterior cerebral artery.

Animals↗