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D A Dawson

Publications and source records attributed to D A Dawson.

14 recordsLinked to original sources

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

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

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

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

The effect of parental alcohol dependence on perceived children's behavior.

The effect of past-year parental alcohol dependence on perceived children's behavioral problems was assessed using data from a general population sample of 3,409 father-child pairs and 5,892 mother-child pairs. Eight percent of the children living in households containing fathers had an alcoholic father; 2% of those living with mothers had an alcoholic mother. Behavioral problems in the 3 months preceding the interview were assessed using a list of 32 indicators and were evaluated by an adult household member, usually the child's mother. The unadjusted odds of a child's being in the top 10th percentile of the behavioral problem distribution were increased by a factor of 1.7 for paternal alcoholism and 2.2 for maternal alcoholism. After adjustment for social and demographic characteristics of the child and family, the odds ratio for alcohol dependence in the mother dropped to 1.6; the odds ratio for paternal alcohol dependence remained at 1.7. Parental alcohol dependence did not interact with social and demographic factors in its association with children's behavioral problems.

Adolescent

Gender differences in alcohol consumption: effects of measurement.

Data from a 1988 survey of US drinking habits and related problems revealed differences in male and female patterns of alcohol consumption. Men were more likely than women to be current drinkers (64 v. 41%), and beer accounted for a larger proportion of their overall intake. Men's average daily ethanol intake was about twice as high as that of women, 17.5 v. 8.9 g. Adjustment for differences in body weight and composition substantially reduced the male-to-female ratio of consumption. Men were more likely than women to be classified as heavy drinkers, and the excess proportion of males so categorized increased with the severity of the measure of heavy drinking.

Adult

Alcohol use and dependence among employed men and women in the United States in 1988.

This paper provides estimates of alcohol consumption and alcohol dependence among employed men and women in the United States. Data from the 1988 National Health Interview Survey indicate that the percentages of drinkers in white-collar occupations are higher than the percentages of drinkers in blue-collar occupations among both men and women; however, the men and women in blue-collar occupations who drink have a higher average daily consumption than drinkers in white-collar occupations. DSM-III-R criteria were used to classify respondents as alcohol-dependent. Consistent with an earlier survey of employed adults in Detroit, the prevalence of alcohol dependence is highest in certain blue-collar occupations (craftsmen, laborers, and service workers among men; machine operators, laborers, and service workers among women). Directions for further research on the occupational and drinking experiences of employed men and women are discussed.

Alcohol Drinking

Family history as a predictor of alcohol dependence.

The effects of various levels of positive family history of alcoholism on the probability of past year alcohol dependence were investigated using a general population sample of 23,152 drinkers 18 years of age and older. Forty percent reported a positive family history. After adjustment for age, race, gender, and poverty and compared with persons with a negative family history, the odds of alcohol dependence were increased by 45% among persons with alcoholism in second or third degree relatives only, by 86% among those with alcoholism in first degree relatives only, and by 167% among those with alcoholism in first and second or third degree relatives. The effects of family history did not vary among population subgroups as defined by age, race, gender, and poverty.

Adolescent

Joint toxic action of binary mixtures of osteolathyrogens at malformation-inducing concentrations for Xenopus embryos.

The joint action of binary mixtures of the osteolathyrogens semicarbazide (SC), beta-aminopropionitrile (beta APN) and penicillamine (PNC) were determined at malformation-inducing concentrations for Xenopus embryos. Tests were static with renewal every 24 h for the 96-h test period. Simultaneous tests on each individual component of the binary mixtures alone gave baseline malformation data (EC50) for joint action analyses. Toxic unit analysis and isobole diagrams were used to determine the type of joint action for 3:1, 1:1 and 1:3 mixtures of each combination. The joint action was concentration additive (strictly additive) for SC with beta APN and response additive (less-than-additive) for SC with PNC and beta APN with PNC. The joint actions were not changed when only osteolathyrogenic lesions, rather than all types of malformations, were considered. The different specific location and character of PNC lesions, as opposed to those for SC and beta APN, may signify a different type of osteolathyrogenic effect for PNC. The mixture testing approach has potential value in determining compounds that act similarly.

Abnormalities, Drug-Induced

Joint action of t-retinoic and valproic acids on Xenopus embryo development.

The joint action of all-trans retinoic acid (RA) with valproic acid (VPA) was examined at malformation-inducing concentrations for Xenopus embryos. The compounds were selected for testing to evaluate malformation as an endpoint for the developmental toxicity of chemical mixtures and to help assess whether joint action types can be related to modes or mechanisms of chemical toxicity for Xenopus. Three mixtures (3:1, 1:1, and 1:3 RA:VPA) were tested in 96 hr static-renewal exposures. Three separate tests were conducted on each mixture. Positive controls were also tested (i.e., 1:0 and 0:1 solutions). Using toxic unit analysis, the joint action for induction of malformations of all types, craniofacial malformations, and microcephaly was response addition, indicating the chemicals are dissimilar and non-interactive. The results support recent joint action studies in providing evidence that similar acting chemicals might be defined as chemicals with the same biochemical/molecular mechanism of action in inducing malformations in Xenopus embryos.

Abnormalities, Drug-Induced

Additive incidence of developmental malformation for Xenopus embryos exposed to a mixture of ten aliphatic carboxylic acids.

A modified FETAX (Frog Embryo Teratogenesis Assay: Xenopus) protocol was used to assess the joint action of ten aliphatic carboxylic acids on Xenopus embryo development. Stock solutions of each acid alone, made up at twice the EC50 of the individual acids, were prepared for testing alone and in a mixture with an equal volume of each acid stock solution. For each treatment, five concentrations and a control dish, each with 25 embryos, were tested for 96 h, with solution renewal every 24 h. The embryos were then fixed and evaluated for gross malformations. For each dish, the number and types of malformations were recorded. An EC50 was calculated for each acid alone and this value was defined as 1.0 toxic unit (TU) for malformation induced by the acid. An EC50 was also calculated for the mixture. The concentration of each acid at the mixture EC50 and the TU values corresponding to these concentrations were then determined. A TU value of 0.990 (0.923-1.060) was obtained for the mixture by adding the TU values for each acid in the mixture. This represents a concentration additive rate of malformation. Microcephaly, TU = 1.09 (1.01-1.18), was the primary malformation, but did not completely account for the response. The concentration additive rate of malformation indicates that all ten acids are likely to induce malformation in Xenopus embryos in a similar manner. Quantitative structure-activity relationship (QSAR) analysis revealed developmental malformation induced by the acids was highly correlated (r2 = 0.979) with hydrophobicity and molar refractivity (r2 = 0.949). The approach has potential application in determining compounds that induce developmental malformations in a similar manner, when metabolism and pharmacokinetic factors are considered.

Abnormalities, Drug-Induced

Family structure and children's health: United States, 1988.

This report describes the family arrangements of children 17 years of age and under and the association between family structure and various demographic and socioeconomic characteristics of the children and their families. The focus of the report is on the relationship between family structure and children's health and well-being. Physical health, educational attainment, and emotional health are compared for children in the four most common types of family. Data are from the 1988 National Health Interview Survey on Child Health.

Adolescent

Recall and reliability of interview data from older women.

Retrospective fertility histories were collected from a purposive sample of 211 white, ever-married women, residing in four metropolitan areas of the USA and belonging to the birth cohorts of 1901-1910. At the time of interview, these women were aged 66 to 76. A random sample of 50 of the original respondents was reinterviewed by telephone on selected topics from the questionnaire. Responses to questions on dates and numbers of marriages, as well as births and other fertility events were coded to show whether the responses were exact, estimated by the respondent, or calculated by the editors. Respondents provided exact answers to an average of 90% of the questions they were asked. Reliability ratios, which were calculated for the above variables as well as ever-use of contraceptive methods, were comparable with those observed in previous studies of women in the childbearing years.

Aged

Malignant otitis externa.

A case is described of malignant otitis externa which was cured by a regime of general and local treatment, including the use of the antibiotic Tobramycin and timely mastoid surgery. The origins, progression, diagnosis and treatment of the disease are discussed with reference to some of the increasingly numerous reports in the literature. Reports disclose an increasing incidence and also an improved prognosis. The former is probably related to the survival of more elderly diabetics and the latter to a better understanding of the disease process and to early medical and, if necessary, surgical treatment. An important feature regarding treatment has been the advent of powerful specific antibiotics including Tobramycin.

Diabetes Complications