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Biomedical subjects

D Dawson

Publications and source records attributed to D Dawson.

At least 19 recordsLinked to original sources

A potential animal model for studying CF heterozygote advantage: genetic variation in theophylline-inducible colonic chloride currents among inbred strains of mice.

We have used Ussing chambers to measure chloride secretion by colonic segments (mucosa, muscularis, and serosa) from various inbred strains of mice. We found lower theophylline-induced Cl- secretion in the DBA/2J than in the C57BL/6J strain. Their F1 showed significantly higher levels of Cl- secretion than did the C57BL/6J parental strain while colonic segments from five recombinant inbred B x D lines ranged between the C57BL/6J and F1 values. No major component of the variation appeared to be associated with alleles of the met oncogene region of chromosome 6 or the H-2 region of chromosome 17.

Animals

Meiotic recombination on artificial chromosomes in yeast.

We have examined the meiotic recombination characteristics of artificial chromosomes in Saccharomyces cerevisiae. Our experiments were carried out using minichromosome derivatives of yeast chromosome III and yeast artificial chromosomes composed primarily of bacteriophage lambda DNA. Tetrad analysis revealed that the artificial chromosomes exhibit very low levels of meiotic recombination. However, when a 12.5-kbp fragment from yeast chromosome VIII was inserted into the right arm of the artificial chromosome, recombination within that arm mimicked the recombination characteristics of the fragment in its natural context including the ability of crossovers to ensure meiotic disjunction. Both crossing over and gene conversion (within the ARG4 gene contained within the fragment) were measured in the experiments. Similarly, a 55-kbp region from chromosome III carried on a minichromosome showed crossover behavior indistinguishable from that seen when it is carried on chromosome III. We discuss the notion that, in yeast, meiotic recombination behavior is determined locally by small chromosomal regions that function free of the influence of the chromosome as a whole.

Bacteriophage lambda

The variability in circadian phase and amplitude estimates derived from sequential constant routines.

Both the constant routine (CR) and the dim light melatonin onset have been suggested as reliable methods to determine circadian phase from a single circadian cycle. However, both techniques lack published studies quantifying the intercycle variability in their phase resolution. To address this question eight healthy male subjects participated in two CRs, 7 days apart. Circadian phase was determined using 3-min samples of core body temperature and two hourly urinary sulphatoxy melatonin excretion rates. Phase and amplitude were estimated using simple (24 h) and complex (24 + 12 h) cosinor models of temperature data and the onset, offset, and a distance-weighted-least-squares (DWLS) fitted acrophase for the melatonin metabolite. The variability in phase estimates was measured using the mean absolute difference between successive CRs. Using the simple 24 h model of temperature data, the mean absolute phase difference was 51 min (SD = 35 min). Using the complex model, the mean absolute phase difference was 62 min (SD = 35 min). Using the DWLS fitted acrophase for the melatonin metabolite, the mean absolute phase difference between CR1 and CR2 was 40 min (SD = 26 min). The results indicate that for CRs a week apart, the mean absolute difference in an individual's phase estimate can vary by 40-60 min depending on the choice of dependent measure and analytic technique. In contrast to the intraindividual variability, the group results showed considerably less variability. The mean algebraic difference between CRs, using temperature- or melatonin-derived estimates, was less than 5 min, and well within the range of normal measurement error.

Adult

A controlled trial of psychological treatment for the irritable bowel syndrome.

One hundred two patients with irritable bowel syndrome were studied in a controlled trial of psychological treatment involving psychotherapy, relaxation, and standard medical treatment compared with standard medical treatment alone. Patients were only selected if their symptoms had not improved with standard medical treatment over the previous 6 months. At 3 months, the treatment group showed significantly greater improvement than the controls on both gastroenterologists' and patients' ratings of diarrhea and abdominal pain, but constipation changed little. Good prognostic factors included overt psychiatric symptoms and intermittent pain exacerbated by stress, whereas those with constant abdominal pain were helped little by this treatment. This study has demonstrated that psychological treatment is feasible and effective in two thirds of those patients with irritable bowel syndrome who do not respond to standard medical treatment.

Abdominal Pain

Timed exposure to bright light improves sleep and alertness during simulated night shifts.

Many of the health and safety problems reported by shift workers result from the chronic sleep deprivation associated with shorter, fragmented daytime sleep. This reduction in the quality and duration of sleep has been attributed to a change in the phase relationship between the work period and the circadian system, timing the propensity for sleep and wakefulness. This study examined the extent to which appropriately timed exposure to bright light would accelerate the circadian readjustment of physiological parameters thought to contribute to impaired performance in shift workers. A control (n = 7) and treatment group (n = 6) underwent a 3-day transition to simulated night work. The treatment group received a single 4-hour pulse of bright light (6,000 lux) between 2400 and 0400 hours on the first night shift and dim light (less than 200 lux) for the remainder of the study. The control group received dim light throughout. By the third night shift, the phase position of the core body temperature rhythm for the treatment group had delayed by 5-6 hours whereas the control group had delayed by only 2-3 hours. When compared to the control group, the greater delay in core temperature rhythm for the treatment group was associated with significantly higher alertness across the night shift and improved sleep quality during the day. By the third day sleep, mean sleep efficiency in the treatment group was not significantly different from normal night sleep. Similarly, onshift alertness was improved relative to the control group. The treatment group did not show the typical decline in alertness observed in the control group between 0300 and 0700 hours. These data indicate that a single 4-hour pulse of bright light between midnight and 0400 hours is effective in ameliorating the sleep and alertness problems associated with transition to night shift.

Adolescent

Fourth report of the cooperative, open-ended study of slowly growing mycobacteria by the International Working Group on Mycobacterial Taxonomy.

The open-ended study of the International Working Group on Mycobacterial Taxonomy is an ongoing project to characterize slowly growing strains of mycobacteria that do not belong to well-established or thoroughly characterized species. In this fourth report we describe two numerical taxonomic clusters that represent subspecies or biovars of Mycobacterium simiae, one cluster that encompasses the erstwhile type strain of the presently invalid species "Mycobacterium paraffinicum," one cluster that is phenotypically very similar to Mycobacterium avium and Mycobacterium intracellulare but may be a separate genospecies, one cluster that appears to be phenotypically distinct from M. avium but reacts with a nucleic acid probe specific for M. avium, and three tentatively defined clusters in proximity to a cluster that encompasses the type strain of Mycobacterium malmoense. Of special practical interest is the fact that one of the latter three clusters is composed of clinically significant scotochromogenic bacteria that can be misidentified as the nonpathogenic organism Mycobacterium gordonae if insufficient biochemical tests are performed.

Agglutination Tests

Genetic and physical analyses of sister chromatid exchange in yeast meiosis.

We have used nonessential circular minichromosomes to monitor sister chromatid exchange during yeast meiosis. Genetic analysis shows that a 64-kb circular minichromosome undergoes sister chromatid exchange during 40% of meioses. This frequency is not reduced by the presence of a homologous linear minichromosome. Furthermore, sister chromatid exchange can be stimulated by the presence of a 12-kb ARG4 DNA fragment, which contains initiation sites for meiotic gene conversion. Using physical analysis, we have directly identified a product of sister chromatid exchange: a head-to-tail dimer form of a circular minichromosome. This dimer form is absent in a rad50S mutant strain, which is deficient in processing of the ends of meiosis-specific double-stranded breaks into single-stranded DNA tails. Our studies suggest that meiotic sister chromatid exchange is stimulated by the same mechanism as meiotic homolog exchange.

Kinetics

Tuberculosis in Australia: an analysis of cases identified in reference laboratories in 1986-88.

The Special Interest Group in Mycobacteria within the Australian Society for Microbiology has carried out a collaborative study of cases of tuberculosis diagnosed in Australian reference laboratories in the years 1986, 1987 and 1988. Annual totals of 574, 584 and 613 respectively, suggest that the incidence of bacteriologically-positive tuberculosis is continuing at 3-4 cases per 100,000 population. The highest rates were detected in males over 50 and females over 65 years of age. Three-quarters of the total cases relate to pulmonary disease. Resistance to at least 1 anti-tuberculosis drug was detected in 78 (12.7%) of isolates tested in 1988. The negligible decline in incidence of tuberculosis in Australia, the high prevalence in S.E. Asian countries, and the fact that HIV-infection is an important risk factor, make it imperative that Australia's diagnostic and management programmes be maintained.

Adolescent

Enhancement of nighttime alertness and performance with bright ambient light.

Objective levels of alertness and performance efficiency were measured in twenty-five healthy young adults during two simulated night shifts. Following the first night shift, during which all subjects worked under dim ambient light (10-20 lux), subjects were assigned to one of three ambient lighting conditions (10-20 lux, 100 lux or 1000 lux) for the second night of work. Subjects exposed to 1000 lux ambient light maintained significantly higher levels of alertness across the 8-hour shift than did subjects exposed to the dimmer lighting conditions. Cognitive performance was also significantly enhanced under the bright light condition, whereas simple reaction time was not. The findings indicate clearly that ambient lighting levels can have a substantial impact on nighttime alertness and performance and that bright ambient illumination may be effective in maintaining optimal levels of alertness during night shift operations.

Adult

Sleep-onset insomniacs have delayed temperature rhythms.

It was predicted from free running and ultradian cycle studies that sleep-onset insomniacs would have endogenous circadian rhythms that were phase delayed compared to good sleepers. Thirteen sleep-onset insomniacs and nine good sleepers were selected to differ only in their sleep-onset latencies as confirmed by polysomnography. their rectal temperatures were measured over a 26-h constant routine and analyzed with best-fit Fourier curves including 24-h fundamental and 12-h harmonic components. The temperature rhythm markers of the insomniacs' rhythms were approximately 2.5 h later than the respective phases of the good sleepers. The usual bedtimes of the insomniacs fell within the "wake maintenance zone" of their delayed temperature rhythm. The good sleepers had typical bedtimes several hours after their "wake maintenance zone" and closer to their body temperature minimum. It was suggested that manipulations to phase advance the insomniacs' rhythms would reduce their sleep-onset latencies. It was also predicted that early morning insomnia results from phase advanced circadian rhythms and that sleep maintenance insomnia results from an abnormal phase relationship between the 24-h temperature rhythm and 12-h sleep-alert rhythm.

Adult

Competence to consent to treatment: a guide for the psychiatrist.

During the last decade there has been increasing pressure to legislate legal rights for psychiatric patients especially in relation to consent to treatment. The attempt to subject the irrationality of psychotic illness to the due process of rational laws has caused problems. Revision of the Ontario Mental Health Act (MHA) has already led to situations in which patients are being incarcerated without treatment because of review board decisions regarding dangerousness and competence. The test in the revised MHA is whether the patient is competent to give or withhold consent for treatment. Existing guidelines for determination of competence to consent to treatment rely upon observer judgement and are open to challenge on grounds of subjectivity. The medical directors of the ten Ontario provincial psychiatric hospitals have therefore developed a guide and schema to operationalize the MHA definitions, a novel feature of which is the examination of competence in such a way as to elicit and capture the patient's own responses upon which an objective determination is made.

Canada

Bright light treatment: are we keeping our subjects in the dark?

Bright light treatments for seasonal affective disorder (SAD) and phase-disturbed circadian rhythms show considerable interindividual variation in response. Many studies have explained this variation in terms of traditional explanations of response variance, i.e., poor diagnostic criteria, poor compliance, etc. This study examined proximity and gaze behavior during illumination as a source of variance in response. Distance from the light source and gaze were varied systematically in order to quantify the discrepancy between perceived and transmitted light. The results indicate that the discrepancy between perceived and transmitted light increases rapidly as a function of distance and gaze. At best, subjects exposed to a transmitted illuminance of 10,000 lux perceived only 20% of the transmitted light, and this dropped rapidly to between 1 and 2% when subjects were more than 3 feet away and not gazing directly at the light source. These results suggest that light treatment protocols may be compromised by lack of attention to compliance and administration factors. These issues may account for much of the response variance observed previously.

Circadian Rhythm

ICU family support group sessions: family members' perceived benefits.

The purpose of this research was to identify the relationship between attending an ICU family support group and the family's appraisal of stress, social support, and hope. In addition, the family members' perceived benefits of attending an ICU family support family support group session does not significantly change stress levels, feelings of hope, and social support. Analysis of data reconfirms that family members of critically ill patients have a tremendous need for information. Although findings revealed that the majority of the family members who attended the support session would recommend attending again, it is unclear whether the support session method is the most beneficial and cost-effective means to support families of critically ill patients.

Adaptation, Psychological

The relationship of agraphia to the severity of dementia in Alzheimer's disease.

Impairment of writing ability was studied in 20 patients with mild to moderate dementia caused by early-onset Alzheimer's disease. A multicomponent analysis was made of a brief narrative writing sample obtained from each patient, and this writing proficiency score was compared with results of standard tests of cognitive function as well as ratings of the degree of dementia. In these patients, significant correlations were observed between this brief test of narrative writing ability and the severity of dementia. An analysis of writing proficiency appears to be a simple means of assessing the severity of dementia caused by Alzheimer's disease. Further studies are needed to show the potential usefulness of such measures of agraphia in subtyping this disease.

Aged

A multicenter study of anticoagulation parameters when using heparin and warfarin.

Anticoagulation with heparin and warfarin is used in the treatment of several diseases including cerebrovascular disease. While the most effective therapeutic range of anticoagulation is unclear, some investigators have found an increased risk of bleeding complications with more intense anticoagulation. Recent studies have suggested that lower levels of anticoagulation may be as efficacious as high levels but with a reduced incidence of bleeding complications. In order to better assess the anticoagulation parameters used by neurologists and house officers, we performed a questionnaire survey at six major medical centers. Responses were obtained from 30 attending neurologists and 52 house officers. Attending physicians and house officers selected mean partial thromboplastin times of 57.7 s and 63.3 s, respectively. The mean prothrombin time (PT) was 21.0 s for attending neurologists and 19.4 s for house officers. The average PT ratio was 1.82 for attending neurologists and 1.69 for house officers. Forty percent of attending neurologists and 17.7% of house officers specified PT ratios of 2.0 or greater. These results indicate that many physicians may be using warfarin in dosages above recommended guidelines.

Blood Coagulation Tests

Magnetic resonance imaging in multiple sclerosis: decreased signal in thalamus and putamen.

High-field strength (1.5 Tesla) magnetic resonance imaging in 15 patients with multiple and extensive white-matter lesions and clinically definite multiple sclerosis delineated a previously undescribed finding of abnormally decreased signal intensity on T2-weighted images in the thalamus and putamen. The decreased signal intensity (preferential decreased T2 relaxation time) is most likely to be related to abnormally increased iron accumulation causing local magnetic field heterogeneities.

Humans