Biomedical subjects

D A Dawson

Publications and source records attributed to D A Dawson.

At least 73 records · Page 4Linked to original sources

PubMed1994

Joint actions of carboxylic acid binary mixtures on Xenopus embryo development: comparison of joint actions for malformation types.

The joint action for malformations induced by 18 binary mixtures of four carboxylic acids was determined, using Xenopus embryos. The acids were selected to evaluate whether joint actions for mixtures changed when the data were analyzed by specific malformations or malformation syndromes as opposed to joint actions determined when any type of malformation was included in the analysis. Each of six binary combinations of the acids were tested three or four times in 96-h static-renewal tests, starting with late-blastula stage embryos. Toxic unit analysis indicated that all but five of 56 possible analyses showed concentration addition joint actions. Concentration addition was observed for all instances in which microcephaly was included as a malformation (with or without other malformations being included) and for all possible mixtures where only eye defects were evaluated. In five instances, evaluating only abnormal gut coiling, the joint action was response addition, including all three mixtures for the valproic acid and pentanoic acid combination. The other 29 analyses which included abnormal gut coiling showed concentration addition. The results indicate that, for chemicals that are structurally similar and induce the same types of defects in frog embryos, there is no significant change in the joint action when the data is analyzed by specific malformations or syndromes rather than by including all malformations together. Abnormal gut coiling, a malformation induced by most toxic chemicals, appears to be less reliable for joint action determination, especially if it is the primary manifestation of abnormal development.

Abnormalities, Drug-Induced↗

PubMed1994

Heavy drinking and the risk of occupational injury.

This study evaluated the association between the frequency of heavy drinking and the risk of occupational injury, using nationally representative data from the 1988 National Health Interview Survey (NHIS). The sample consisted of 29,192 adults who were employed at some time during the year preceding the NHIS interview. Overall, 7.2% reported an on-the-job injury during the preceding year, but the rates were higher--about 13%--for those employed as skilled or unskilled laborers or who reported engaging in repeated strenuous physical activity at work. Slightly more than one-fourth of the employed adults reported at least one occasion of drinking five or more drinks during the preceding year. After adjusting for the effects of age, gender, education, occupation, and strenuous job activity, the odds of occupational injury increased with frequency of heavy drinking, with odds ratios varying from 1.08 (one occasion of heavy drinking) to 1.74 (daily heavy drinking). Odds ratios were decreased slightly by the inclusion of smoking as a control variable, indicating that some of the excess risk of injury among heavy drinkers may reflect their greater propensity to take health-related risks rather than direct effects of ethanol. The odds ratios also were slightly lower when the analysis was restricted to current drinkers, suggesting that the risk of work injury was increased by light or moderate as well as heavy drinking.

Accidents, Occupational↗

PubMed1994

Are men or women more likely to stop drinking because of alcohol problems?

Using a national population sample of adults who had ever consumed at least 12 drinks per year, men and women were compared in terms of the proportions who had stopped drinking because of alcohol problems. Overall, 24% of the male drinkers and 31% of the female drinkers had stopped drinking as of the time of interview, but men were more likely than women to have stopped drinking because of alcohol-related problems (4.3 vs. 2.3%). After using survival techniques to adjust for women's greater competing risk of stopping drinking for other reasons and men's greater exposure time due to their earlier initiation of drinking, the conditional probabilities of having stopped drinking because of alcohol problems were almost identical for men and women during the first 15 years of their drinking histories. Thereafter, the conditional probabilities were about 50% higher for men than for women. The observed durations of drinking history were about five years longer for men than women. After controlling for sociodemographic characteristics, family history of alcoholism, and patterns of alcohol consumption, there was no gender difference in the hazard of stopping drinking because of alcohol problems among persons who drank alcohol on less than a daily basis during their period of heaviest consumption. However, among daily drinkers, the hazard of stopping drinking because of alcohol problems was greater for women than men, by a factor of 1.5 to 3, depending on quantity of consumption and interval since first drink.

Adolescent↗

PubMed1994

A study of the gender differences in morbidity among individuals diagnosed with alcohol abuse and/or dependence.

The majority of studies on medical consequences of excessive alcohol consumption have been carried out with male subjects, mostly from clinical or hospitalized samples. The purpose of this report was to study differences in morbidity outcomes of men and women among respondents diagnosed with alcohol abuse and/or dependence. Utilizing data from the 1988 National Health Interview Survey, this study compared several indicators of physical morbidity among male and female respondents meeting the criteria for Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R; American Psychiatric Association, 1987) alcohol abuse and/or dependence. The results revealed complex gender differences, not all of which can be explained by differences in sociodemographic characteristics or drinking practices. Moreover, the results indicated that it is inadequate to generalize results based on morbidity data of men with alcohol abuse and/or dependence to their female counterparts or female drinkers. Implications of these findings are discussed.

Adolescent↗

PubMed1994

Consumption indicators of alcohol dependence.

This Data Note evaluates various dichotomous measures of alcohol consumption as screeners for past-year alcohol dependence. The analysis is based on data from 22,102 current drinkers interviewed in the 1988 US National Health Interview Survey. The consumption indicators include measures of average daily intake, frequency of heavy drinking, usual quantity and frequency of drinking and various combinations of these measures. The measures based on frequency of heavy drinking are the most strongly correlated with dependence, but none of the consumption indicators have the sensitivity or specificity of screeners based on alcohol-related problems. Most of the consumption items considered in this analysis screen for dependence more successfully among men than among women.

Alcohol Drinking↗

PubMed1994

Anti-ischaemic efficacy of a nitric oxide synthase inhibitor and a N-methyl-D-aspartate receptor antagonist in models of transient and permanent focal cerebral ischaemia.

1. We have recently developed a new model of transient focal ischaemia in the rat utilising topical application of endothelin-1 to the left middle cerebral artery (MCA). In order to validate this approach the present study assessed the neuroprotective efficacy of the NMDA receptor antagonist dizocilpine (MK-801) in the endothelin-1 model. The anti-ischaemic efficacy of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) was subsequently evaluated, and contrasted with its efficacy against permanent focal ischaemia, to determine the utility of the endothelin-1 model for identification of novel pharmacoprotective agents. 2. MK-801 (0.12 mg kg-1 bolus, 108 micrograms kg-1 h-1 infusion i.v., either 1 or 2.5 h pre-transient MCA occlusion (MCAO)) induced hypotension that persisted for approximately 1.5 h so that mean arterial blood pressure (MABP) at the time of MCAO was significantly lower in the 1 h group compared with control (MABP: 86 +/- 11, 68 +/- 6 and 84 +/- 4 mmHg (mean +/- s.d.) for saline, 1 h MK-801 and 2.5 h MK-801 groups respectively). The 2.5 h pretreatment schedule resulted in significant reduction (71%) in the volume of hemispheric damage (assessed 4 h post onset of ischaemia) while the 1 h pretreatment schedule did not (volumes of hemispheric damage: 59 +/- 38, 51 +/- 51 and 17 +/- 28 mm3 for saline, 1 h and 2.5 h MK-801 groups). 3. Thus the considerable neuroprotective effect of MK-801 in the endothelin-1 model of transient focal cerebral ischaemia was highly sensitive to drug-induced hypotension. This result is in contrast to previous studies of permanent MCAO where MK-801-induced hypotension did not compromise its neuroprotective action.4. L-NAME (3 mg kg-1, i.v. 30 min pre-MCAO) moderately, but significantly, reduced (16%) the volume of ischaemic damage 4 h post-permanent MCA occlusion, whereas the 29% reduction in volume of damage achieved in the model of transient focal ischaemia did not attain significance due to the greater variability associated with this model. L-NAME did not significantly alter MABP in either model.5. The modest neuroprotection achieved with NO synthase inhibition suggests NO is of relatively minor importance as a mediator of neurotoxicity following permanent focal cerebral ischaemia. In addition the comparable efficacy of L-NAME against transient focal ischaemia suggests the presence of reperfusion does not enhance the contribution of NO to neuronal injury in the acute (4 h) phase following a focal ischaemic insult.

Amino Acid Oxidoreductases↗

PubMed1994

Nitric oxide and focal cerebral ischemia: multiplicity of actions and diverse outcome.

The original observation that inhibitors of nitric oxide (NO) synthesis can antagonize glutamate toxicity in cell culture has led to extensive investigation of the role of NO in the pathophysiology of cerebral ischemic injury in vivo. However, studies of the efficacy of NO synthase inhibitors in models of focal cerebral ischemia have generated widely disparate findings, ranging from dramatic neuroprotection to exacerbation of ischemic damage. This review summarizes these studies and proposes that their apparently contradictory findings can be reconciled by viewing the results as a continuum of response that reflects the many and diverse physiological actions of NO. Thus, differences in experimental design between studies can alter the balance between these NO-controlled processes and result in the transformation of an overt neuroprotective effect of NO synthesis inhibition into one of exacerbation of ischemic injury. Thus, this review also identifies some of the most important physiological and pathophysiological functions of NO (and the consequences of their inhibition by NO synthase inhibitors) that may interact to determine outcome after a focal cerebral ischemic insult. A clearer appreciation of the potential therapeutic utility of both NO synthesis inhibitors and NO donors will emerge only when the complexity of their effects on mechanisms that interact to determine the extent of ischemic damage in vivo are more fully defined and understood.

Amino Acid Oxidoreductases↗

PubMed1993

Cerebrovascular effects of NG-nitro-L-arginine methylester are conserved under halothane anaesthesia.

The effects of the nitric oxide synthesis inhibitor NG-nitro-L-arginine methylester (L-NAME) on mean arterial blood pressure (MABP) and local cerebral blood flow were determined in conscious and halothane-anaesthetised rats. Thirty minutes post-drug administration in conscious rats L-NAME (30 mg kg-1 i.v.) induced significant hypertension (MABP 132 +/- 2 mmHg and 163 +/- 6 mmHg (means +/- S.D.) for saline and L-NAME groups respectively) and significant hypoperfusion throughout the brain (mean +/- S.D. reduction in cerebral blood flow 27.3 +/- 5.9% compared with controls). In contrast, under halothane anaesthesia, L-NAME did not significantly change MABP but significant reductions in cerebral blood flow (43.2 +/- 3.7%) were observed. Thus the cerebrovascular response to L-NAME is conserved under halothane anaesthesia despite attenuation of the peripheral vasoconstrictive action.

Anesthesia, Inhalation↗

PubMed1993

Joint action of benzoic hydrazide and beta-aminopropionitrile on Xenopus embryo development.

Binary mixtures of the osteolathyrogens benzoic hydrazide and beta-aminopropionitrile were tested to determine the joint action for these chemicals, by evaluating induction of malformation and osteolathyrism in developing frog embryos. Exposures, starting with late-blastula stage embryos, were for 96-h with solution renewal every 24-h. Five treatments were examined, each chemical alone (i.e., 1:0 and 0:1 solutions) and three mixtures (i.e., 3:1, 1:1, and 1:3). Following exposure, embryos were evaluated grossly and the incidences of all types of malformations and osteolathyrogenic lesions were determined. Toxic unit analysis and isobole diagrams indicated these chemicals were concentration additive in inducing malformations and osteolathyrism. Therefore, benzoic hydrazide and beta-aminopropionitrile induce osteolathyrism, in Xenopus embryos, in a similar manner.

Aminopropionitrile↗

PubMed1993

Gender effects in diagnosing alcohol abuse and dependence.

Using a national population sample of 43,809 adults, male and female responses were compared for 41 indicators of alcohol abuse and dependence. While men reported all indicators more often than did women, the male to female ratio of positive responses varied according to both the construct represented by the item and its underlying prevalence. Items that might be construed as signs of weakness-physical effects, psychological effects, and loss of control or powerlessness--had lower male/female ratios than other items. Excess male prevalence was greatest for the least prevalent indicators. The paper presents alternative interpretations of these findings and discusses their implications for diagnostic classification.

Adolescent↗

PubMed1993

Comparative joint actions of semicarbazide and thiosemicarbazide on induction of malformations and osteolathyrism in mixtures with benzoic hydrazide.

A developed mixture testing protocol, evaluating malformation of Xenopus embryos, was used to examine the joint actions of semicarbazide (SC) and thiosemicarbazide (TSC) with benzoic hydrazide (BZH). These compounds were selected to evaluate the effect of a substitution of sulfur for oxygen on osteolathyrism induced in Xenopus embryos. Binary combinations of SC with BZH and TSC with BZH were tested using three mixture ratios for each combination. Each compound was simultaneously tested alone in 96 h static-renewal tests, starting with late-blastula stage embryos. Toxic unit analysis, evaluating induction of malformations in general and osteolathyrism specifically, indicated the joint action for each combination was concentration addition. The results indicate that the three chemicals are similar and non-interactive and are likely to induce osteolathyrism by the same primary mechanism of action.

Animals↗

PubMed1993

Inhibition of nitric oxide synthesis: effects on cerebral blood flow and glucose utilisation in the rat.

The consequences of inhibition of nitric oxide synthesis on local CBF and glucose utilisation have been studied in the conscious rat using the specific nitric oxide synthase inhibitor Ng-nitro-L-arginine methyl ester (L-NAME; 30 mg kg-1 i.v.). Local CBF and glucose utilisation were assessed with the [14C]iodoantipyrine and the 2-deoxy-D-[14C]glucose autoradiographic techniques, respectively. L-NAME induced prolonged (> 3 h) reductions in local CBF throughout the CNS with concomitant increases in arterial blood pressure. For example, 1 h post L-NAME, CBF dropped from 79 +/- 4 to 45 +/- 1 ml 100 g-1 min-1 in cerebellum, from 76 +/- 4 to 47 +/- 2 ml 100 g-1 min-1 in medulla oblongata, and from 117 +/- 6 to 72 +/- 2 ml 100 g-1 min-1 in cortex. L-NAME produced sustained elevations (e.g., 46 +/- 2 mm Hg at 1 h after bolus administration) in mean arterial blood pressure throughout the period evaluated. Despite evidence implicating nitric oxide in neuronal signalling, L-NAME did not significantly influence CNS functional activity, as measured by local rates of glucose utilisation, in any neuroanatomical region examined. Consequently, the normal ratio of blood flow to glucose use throughout the brain was significantly reduced in the presence of L-NAME, although the hierarchy of blood flow levels in different neuroanatomical regions was preserved. These results are consistent with the involvement of nitric oxide in the tonic control of cerebral tissue perfusion.

Amino Acid Oxidoreductases↗

PubMed1993

Patterns of alcohol consumption: beverage effects on gender differences.

This Data Note reports findings from 22,102 current drinkers who responded in the US National Interview Survey in 1988. Mean estimated alcohol intake of males exceeded that of females by a factor of two. Males drank more per occasion (ratio 1.45) and drank on more occasion (1.41). Mean ethanol content per drink was slightly less for males (ratio 0.95) attributable to a decreased proportion of drinks being wine and liquor. When beverage preferences were taken into account, the drinking patterns of males and females showed no meaningful differences among persons with similar levels of overall ethanol intake. The results do not support the view that the difference between ethanol consumption of males and females are due primarily to males drinking more per occasion. Apparent differences in drinking patterns are attributable to differences in preferred beverage.

Alcohol Drinking↗

PubMed1993

Relative frequency of heavy drinking and the risk of alcohol dependence.

Data from a national representative sample of US adults were analyzed to determine the association between the relative frequency of heavy drinking (the proportion of drinking occasions on which 5+ drinks were consumed) and past-year alcohol dependence, adjusting for the influences of average ethanol intake and sociodemographic factors. Fifty-seven percent of current drinkers reported never drinking 5+ drinks, and 21% drank 5+ drinks at least once but on less than 10% of all drinking occasions. Nine percent reported drinking 5+ drinks on at least half of all drinking occasions. Average daily intake was positively correlated with the relative frequency of heavy drinking, and both consumption measures were positively associated with the risk of alcohol dependence. Increases in either relative frequency of heavy drinking or average ethanol intake reduced, but did not eliminate, the effect of the other on the risk of dependence. The excess risk of dependence associated with frequent heavy drinking varied among population subgroups and was increased by age, education, and female gender.

Adolescent↗

PubMed1992

Inhibition of nitric oxide synthesis does not reduce infarct volume in a rat model of focal cerebral ischaemia.

The effect of the nitric oxide (NO) synthesis inhibitor Ng-nitro-L-arginine methylester (L-NAME) on ischaemic brain damage was determined in a rat model of focal cerebral ischaemia. Ischaemia was induced by permanent occlusion of the left middle cerebral artery (MCA) and infarction assessed 4 h post-occlusion by quantitative histopathology. L-NAME (30 mg/kg s.c.), administered 30 min pre- and 30 min post-MCA occlusion, did not significantly alter the volume of ischaemic damage in the cerebral hemisphere, neocortex or caudate nucleus compared with saline controls. This result provides no support for the view that NO generation is a key component in the post-ischaemic cascade leading to acute neuronal death.

Animals↗

PubMed1992

Autoradiographic evaluation of forskolin and D1 dopamine receptor binding in a rat model of focal cerebral ischaemia.

Post-ischaemic changes in forskolin and D1 dopamine receptor (labelled with SCH23390) binding sites were evaluated in a rat unilateral middle cerebral artery occlusion (MCA) model. The changes in binding were assessed acutely (2 h post-MCA occlusion) in relation to local cerebral blood flow (lCBF) and chronically (24 h post-MCA occlusion) in relation to histopathological alterations. Two hours following occlusion lCBF was significantly reduced throughout the territory of the MCA. Despite the widespread hypoperfusion, significant reductions in binding were only observed in the dorsolateral caudate nucleus--the region with the most profound reduction in blood flow (6% of the control contralateral lCBF value). Forskolin binding sites were reduced to 40% of the contralateral value while D1 binding sites were reduced to 80% of the contralateral value. Analysis of the relationship between forskolin binding and CBF in the caudate nucleus revealed that the ischaemic threshold for alteration in forskolin binding sites 2 h after MCA occlusion was approximately 34 ml/100 g/min. Twenty-four h post-occlusion forskolin binding sites were further reduced in the dorsolateral caudate nucleus (to 6% of contralateral) while D1 binding showed minimal reduction from that observed at 2 h. The areas of reduced binding corresponded to the area of histopathological change in the caudate nucleus and rostral neocortex. In conclusion, reduction in forskolin binding progresses further than reduction in D1 binding within the first 24 h following focal cerebral ischaemia. For both forskolin and D1 binding sites, the areas of reduced binding 24 h post-MCA occlusion predicted the area of histopathological change.

Animals↗

PubMed1992

Joint actions of developmental toxicants in Xenopus embryos: binary mixtures of DNA synthesis inhibitors.

The joint toxic action for each of three binary combinations of DNA synthesis inhibitors was examined at concentrations that induce malformations in Xenopus laevis embryos. The three compounds, hydroxyurea, cytosine arabinoside, and 5-fluorouracil, which each inhibit a different enzyme involved in DNA synthesis, were selected for joint action testing to help determine whether joint action types are related to general modes of action (e.g., inhibit DNA synthesis) or to specific biochemical/molecular mechanisms. Three mixtures were tested, in 96-hr static-renewal tests, for each combination. Each combination was tested on three separate occasions. Using toxic unit analysis, the joint action for induction of malformations was generally antagonism, although response addition was observed for certain mixtures. An antagonistic joint action represents the phenomenon of interaction. Therefore, the tests were ineffective in determining whether a concentration addition joint action depicts two compounds that induce malformations by the same general mode of action or by the same specific mechanism of action.

Animals↗

PubMed1992

Parental history of alcoholism and probability of marriage.

Personal interview data for 16,795 U.S. adults 18-39 years of age were analyzed to assess the effect of positive parental history of alcoholism on the probability of ever having been married. The data were collected as part of the 1988 National Health Interview Survey. The effects of parental history were estimated using logistic regression models that adjusted for age, race, gender, and respondent history of alcohol problems. Nonblack adults who lived with one or more alcoholic parents when growing up were 50% more likely ever to have been married than those with no parental history. The effect was of the same magnitude regardless of whether the alcoholic parent was the mother or the father, but was larger if both parents were reported to be alcoholics. Among blacks, positive parental history of alcoholism did not affect the odds of marriage. The greater likelihood of early marriage among children of alcoholics may help explain their excess risk of marital disruption.

Adolescent↗