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Biomedical subjects

D C Thompson

Publications and source records attributed to D C Thompson.

At least 73 records · Page 4Linked to original sources
PubMed1993

Biological and toxicological consequences of quinone methide formation.

Quinone methides are a class of reactive, electrophilic compounds which are capable of alkylating cellular macromolecules. They are formed during xenobiotic biotransformation reactions and are hypothesized to mediate the toxicity of a large number of quinone antitumor drugs as well as several alkylphenols. In addition, oxidation of specific endogenous alkylphenols (e.g. coniferyl alcohol) and alkylcatechols (e.g. N-acetyldopamine, dopa) to quinone methides plays an important role in the synthesis of several complex plant and animal polymers, including lignin, cuticle and melanin. The role of quinone methides in these various processes is reviewed.

Animals↗
PubMed1993

Cost-effectiveness analysis of bicycle helmet subsidies in a defined population.

OBJECTIVE: To examine the potential effects of bicycle safety helmet cost subsidy on bicycle head injury rates and costs. DESIGN: Using empiric data on the incidence and costs of bicycle injuries to children, we examined the hypothetical effects of various bicycle helmet subsidies in a cost-effectiveness analysis. A hypothetical cohort of 100,000 5- through 9-year-olds was followed for 5 years after helmet cost subsidization. Sensitivity analyses were done of three different levels of safety helmet subsidy ($5, $10, $15), three discount rates (2%, 4%, 6%), 10 levels of safety helmet use ranging from 10% to 100%, and the occurrence or nonoccurrence of catastrophic head injuries. PATIENTS: Forty-three children 5 through 9 years of age and 27 children 10 through 14 years of age with head injuries due to bicycling were identified through emergency department surveillance of a population of 29,533. SETTING: Group Health Cooperative of Puget Sound, a large health maintenance organization. OUTCOME MEASURES: Bicycle head injuries prevented and the savings or costs associated with various subsidy, safety helmet use, and discount rates. RESULTS: Hypothetically, an increase in bicycle helmet use rates to 40% to 50% due to subsidies of $5 or $10 prevents 564 to 840 head injuries in a cohort of 100,000 5- through 9-year-olds over 5 years. Under these conditions and a 2% discount rate, cost savings ranging from $189,207 to $427,808 will result when catastrophic head injuries are included in the analysis. CONCLUSION: Subsidization of bicycle safety helmets to achieve a cost of $14 to $20 per helmet and use rates of 40% to 50% will likely prove cost-effective. Empirical evidence from a Seattle campaign suggests that such helmet use rates are achievable.

Adolescent↗
PubMed1992

Enhanced mutagenicity of anisidine isomers in bacterial strains containing elevated N-acetyltransferase activity.

In previous studies on the mutagenicity of anisidine isomers, the ortho isomer was considered to be mutagenic towards standard Ames tester strains, while the para isomer gave equivocal results. In the present study we show that both para- and ortho-anisidine isomers are mutagenic in a Salmonella typhimurium tester strain containing elevated levels of N-acetyltransferase (YG1029). p-Anisidine gave a positive mutagenic response using either hamster S9 or ram seminal vesicle microsomes (RSVM) as an activating system, while o-anisidine gave a positive response only with the hamster S9 fraction. The mutagenic response from p-anisidine was greater than with o-anisidine in each case. In tests with p-anisidine and RSVM, the addition of arachidonic acid was not necessary to observe a mutagenic response. Catalase produced a dose-dependent decrease in the mutagenic response with p-anisidine and RSVM; this indicates that endogenous hydrogen peroxide from the bacteria acts as a substrate for the peroxidase activity of RSVM prostaglandin H synthase. These results demonstrate that both anisidine isomers are mutagenic and that N-acetyltransferase enzymes play an important role in their metabolism to mutagenic species.

Arylamine N-Acetyltransferase↗
PubMed1992

Atypical presynaptic alpha-adrenoceptor modulation of neurally-mediated cholinergic responses in guinea-pig tracheal smooth muscle.

Cholinergic excitatory nerves in guinea-pig trachea are subject to inhibitory control by presynaptic alpha 2-adrenoceptors. Recently, the nature of these receptors has come into question insofar as the presynaptic inhibitory effects of the alpha 2-adrenoceptor agonist, clonidine, in the guinea-pig trachea have been shown to be antagonized by the alpha 2-adrenoceptor antagonist, yohimbine, as well as the alpha 1-adrenoceptor antagonist, prazosin. This inhibitory action of prazosin had not been described previously in the airways and may relate to the use of norepinephrine rather than clonidine as the alpha-adrenoceptor agonist in earlier studies. The present study evaluates the susceptibility of norepinephrine-induced inhibition of neurally-mediated cholinergic excitatory responses to antagonism by prazosin and yohimbine under conditions identical to those which showed clonidine to be sensitive to these antagonists. In tissues pretreated with guanethidine, propranolol and indomethacin, norepinephrine (1 microM) induced a 37-fold rightward shift of the frequency-response curve for neurally-mediated cholinergic contractions which was reversed partially by pretreatment of tissues with yohimbine. Norepinephrine also caused a concentration-dependent inhibition of cholinergic 'twitch' responses induced by intermittent (1 Hz) nerve stimulation. This action of norepinephrine was antagonized in a concentration-dependent manner by yohimbine but was unaffected by prazosin. These results indicate that in guinea-pig trachea the presynaptic inhibitory actions of norepinephrine on cholinergic nerves are mediated via classical alpha 2-adrenoceptors, i.e. receptors that can be blocked by yohimbine but not by prazosin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Omega-conotoxin-sensitive calcium channels modulate autonomic neurotransmission in guinea pig airways.

omega-Conotoxin GVIA, a peptide derived from the marine snail Conus geographus, is an antagonist of the neuronal N type voltage-sensitive calcium channels associated with neurotransmitter release. The present study investigated effects of this peptide on neurally mediated responses in airways isolated from the guinea pig to determine whether airway nerves are modulated by omega-conotoxin-sensitive calcium channels. Electrical field stimulation was used to induce neurally mediated tachykininergic excitatory responses in guinea pig bronchus and cholinergic excitatory and nonadrenergic noncholinergic inhibitory responses in guinea pig trachea. Exogenous agonists were administered to induce contractile (acetylcholine, substance P) or relaxation (sodium nitroprusside) responses. Tissues were incubated with omega-conotoxin (1 microM) or its vehicle (10 mM acetic acid) for 30 min before establishing frequency- or concentration-response relationships to the various stimuli. Frequency-response curves for neurally mediated cholinergic, nonadrenergic nocholinergic inhibitory and tachykininergic responses were shifted to the right by omega-conotoxin to a similar extent (4- to 5-fold). omega-Conotoxin had no effect on contractile responses elicited by exogenous acetylcholine or substance P or on relaxations induced by sodium nitroprusside. These findings indicate that neurotransmission in afferent tachykininergic kininergic nerves and in efferent cholinergic excitatory and nonadrenergic noncholinergic inhibitory nerves in the airways is modulated by a prejunctional omega-conotoxin-sensitive mechanism.

Acetylcholine↗
PubMed1991

Metabolism and cytotoxicity of eugenol in isolated rat hepatocytes.

The metabolism and toxic effects of eugenol (4-allyl-2-methoxyphenol) were studies in isolated rat hepatocytes. Incubation of hepatocytes with eugenol resulted in the formation of conjugates with sulfate, glucuronic acid and glutathione. The major metabolite formed was the glucuronic acid conjugate. Covalent binding to cellular protein was observed using [3H]eugenol. Loss of intracellular glutathione and cell death were also observed in these incubations. Concentrations of 1 mM eugenol caused a loss of over 90% of intracellular glutathione and resulted in approximately 85% cell death over a 5-h incubation period. The loss of the majority of glutathione occurred prior to the onset of cell death (2 h). The effects of eugenol were concentration dependent. The addition of 1 mM N-acetylcysteine to incubations containing 1 mM eugenol was able to completely prevent glutathione loss and cell death as well as inhibit the covalent binding of eugenol metabolites to protein. Conversely, pretreatment of hepatocytes with diethylmaleate to deplete intracellular glutathione increased the cytotoxic effects of eugenol. These results demonstrate that eugenol is actively metabolized in hepatocytes and suggest that the cytotoxic effects of eugenol are due to the formation of a reactive intermediate, possibly a quinone methide.

Animals↗
PubMed1991

Injuries to children and adolescents: impact on physical health.

Disability resulting from injuries was examined in a health maintenance organization population of children and adolescents 0 through 19 years of age. The physical health status instrument from the Rand Health Insurance Study was used to evaluate functional outcome of patients seen in the emergency room and outpatient clinic. Overall, 55.1% of individuals had limitations in their usual activities during the week following injury; 16.4% and 3.8% were not yet back to full activities after 1 week and 1 month, respectively. Individuals 10 years of age and older had more functional impairment than did younger children. Restrictions were greatest for fractures/dislocations and sprains and for injuries due to sports, play/recreational activities, and falls.

Activities of Daily Living↗
PubMed1990

DMSO.

Explore the source record for details and available documents.

Administration, Topical↗
PubMed1990

Nicotinic agonist modulation of feline bronchomotor tone.

1. The bronchomotor actions of three nicotinic cholinoceptor agonists were investigated in anaesthetized, mechanically ventilated cats. The agonists were administered intravenously after increasing baseline airways smooth muscle tone with an infusion of 5-hydroxytryptamine. 2. Acetylcholine induced a biphasic change in lung resistance, characterized by initial bronchoconstriction followed by bronchodilation. The specific nicotinic cholinoceptor agonists, nicotine and dimethylphenylpiperazinium (DMPP), principally induced bronchodilator responses, although initial bronchoconstrictor phases were observed occasionally. 3. All bronchoconstrictor phases were sensitive to muscarinic cholinoceptor blockage with atropine. DMPP-induced bronchodilator responses were adrenergic in nature, whereas those induced by either nicotine or acetylcholine resulted from a combination of adrenergic and non-adrenergic influences. 4. It is concluded that intravenously administered nicotinic cholinoceptor agonists exert varying actions on feline bronchomotor tone and that these actions result from activation of different autonomic inputs.

Acetylcholine↗
PubMed1990

Prostaglandin H synthase and xenobiotic oxidation.

We have attempted in this article to summarize and review cooxidation reactions that occur during the metabolism of AA and potential roles that these reactions can play in the activation and detoxification of chemicals. This review summarizes approximately 15 years of intensive investigation by a number of laboratories, and as such not all studies are cited, and in some cases data are not discussed with the emphasis that the original investigators may have intended. The major focus of many of these studies has been toward carcinogenesis. In the future, emphasis may shift to the formation of metabolites that will lead to other toxic effects. The cooxidation reactions that occur during AA metabolism are dependent upon the peroxidase activity of PHS. For some chemicals that are not cosubstrates, the epoxidation reactions that occur are dependent upon the subsequent formation of peroxyl radicals. A large and diverse number of chemicals are metabolized by an equally large and diverse number of chemical reactions. The unifying theme is the free radical nature of these oxidations. The subsequent reactions that these chemicals undergo is dictated by the nature of the free radical and the environment in which it is generated. Ample evidence now exists for the contribution of these free radical-mediated reactions not only in the formation of toxic metabolites, but also in some cases in the detoxification of chemicals. The overriding factor for this type of metabolism to occur is the relative concentrations in the specific tissue of PHS and peroxyl radicals with respect to other activating systems, particularly the monooxygenase system. In vivo investigations support the importance of the peroxidase and peroxyl radical systems in both activation and detoxification of chemicals in extrahepatic tissues.

Animals↗
PubMed1990

Nonadrenergic bronchodilation induced by high concentrations of sulfur dioxide.

SO2 is an environmental pollutant known to elicit bronchospasm in susceptible subjects. We observed that brief exposure of artificially bronchoconstricted cats to high concentrations of SO2 induces a bronchodilator response. This study assessed the characteristics of this response and examined various mechanisms that might underlie it. Cats were anesthetized with diallylbarbital-urethan, and airway smooth muscle tone, measured by lung resistance and dynamic lung compliance, was elevated with a continuous infusion of 5-hydroxytryptamine. Administration of 10 breaths of SO2 via a tracheostomy induced concentration-dependent bronchodilation in the range 100-1,000 parts/million. Only infrequently was bronchoconstriction observed before bronchodilation. SO2-induced bronchodilator responses were unaffected by pretreatment with intravenous atropine or propranolol, establishing them as nonadrenergic noncholinergic (NANC) in origin. Neither the ganglionic blocking agent hexamethonium nor the nerve toxin tetrodotoxin influenced the SO2-induced bronchodilation, thus excluding a role for central or local autonomic reflexes in the response. Efforts to modulate the response by pretreatment with the cyclooxygenase inhibitor indomethacin or the mediator release inhibitor cromolyn sodium also were unsuccessful. Administration of acidic aerosols failed to mimic the SO2-induced bronchodilator response. Although the mechanism whereby SO2 induces bronchodilation under these experimental conditions remains unclear, release of a NANC inhibitory transmitter from a neural, epithelial, or other cellular source via a mechanism insensitive to both tetrodotoxin and cromolyn is a distinct possibility. An intrinsic NANC inhibitory system may exist in feline airways functioning as a local regulator of bronchomotor tone and possibly serving to override responses to strong, potentially asphyxial bronchoconstrictive stimuli.

Animals↗
PubMed1990

Enzymatic modulation of vasoactive intestinal peptide and nonadrenergic noncholinergic inhibitory responses in guinea pig tracheae.

The airways of the guinea pig are innervated by four types of autonomic nerves: cholinergic excitatory, adrenergic inhibitory, nonadrenergic noncholinergic (NANC) excitatory, and NANC inhibitory. Tachykinins (neurokinins A and B and substance P) are believed to mediate NANC excitatory responses, and vasoactive intestinal peptide (VIP) has been proposed as the chemical mediator of the NANC inhibitory system. Enzymatic degradation represents an important means by which the biologic actions of neurotransmitters are terminated. In the present study, relaxation responses of guinea pig tracheae to NANC nerve stimulation and to exogenous VIP administration were compared in the absence and presence of various peptidase inhibitors. NANC inhibitory responses elicited by electrical field stimulation were unaffected by aprotinin or soybean trypsin inhibitor but were depressed by thiorphan or leupeptin. Concentration-response curves to exogenous VIP were shifted to the left by soybean trypsin inhibitor but were not affected by aprotinin, leupeptin, or thiorphan. After tachykinin depletion with capsaicin, thiorphan also induced a leftward shift in the VIP concentration-response curve. Under the same conditions, thiorphan failed to influence NANC inhibitory responses. These results indicate that the NANC inhibitory neurotransmitter is not metabolized by enzymes susceptible to inhibition by aprotinin, leupeptin, soybean trypsin inhibitor, or thiorphan and, accordingly, distinguish NANC nervous responses from those induced by VIP. The results also suggest that the NANC excitatory system can interact functionally with the NANC inhibitory system, as evidenced by the blunting of NANC relaxation responses following inhibition of tachykinin metabolism and elimination of this effect by capsaicin.

Animals↗
PubMed1990

Incidence of bicycle-related injuries in a defined population.

Population-based incidence rates for head injuries and total injuries resulting from bicycle crashes were calculated in a Seattle, Washington health maintenance organization population. Overall rates were 163 per 100,000 for all injuries and 42/100,000 for head injuries. Individuals between 5 and 14 years of age are at highest risk for bicycle-related injuries. The data are presented for their potential utility in program planning.

Age Factors↗
PubMed1990

A case-control study of the effectiveness of bicycle safety helmets in preventing facial injury.

In a case-control study we sought to assess the potential effectiveness of helmets in preventing facial injuries. Our study included 212 bicyclists with facial injuries and 319 controls with injuries to other body areas, who were treated in emergency rooms of five Seattle area hospitals over a one-year period. Using regression analyses to control for age, sex, education and income, accident severity, and cycling experience we found no definite effect of helmets on the risk of serious facial injury (odds ratio 0.81; 95 percent confidence interval = 0.45, 1.5), but protection against serious injuries to the upper face (odds ratio 0.27; 95% CI = 0.1, 0.8). No protection was found against serious injuries to the lower face. The independent effect of helmet use on facial injury was difficult to isolate due to the association of head and facial injuries. Our results suggest that bicycle helmets as presently designed may have some protective effect against serious upper facial injuries.

Adolescent↗
PubMed1990

Presynaptic alpha adrenoceptor modulation of neurally mediated cholinergic excitatory and nonadrenergic noncholinergic inhibitory responses in guinea pig trachea.

Cholinergic and nonadrenergic noncholinergic (NANC) excitatory nerves in guinea pig trachea are subject to presynaptic alpha-2 adrenoceptor inhibitory control. Although the trachea is also innervated by NANC inhibitory nerves, little is known about their presynaptic regulation. The present study assessed the capacity of alpha-1 and alpha-2 adrenoceptor agonists to modulate NANC inhibitory nerves and for comparison, cholinergic excitatory nerves in guinea pig trachea. To eliminate effects of intrinsic sympathetic nerve stimulation and prostanoid production, tissues were pretreated with guanethidine, propranolol and indomethacin. The alpha-2 adrenoceptor agonist, clonidine (1 microM), induced a 12-fold rightward shift of the frequency-response curve for neurally mediated cholinergic contractions but had no effect on the concentration-response curve for exogenously administered acetylcholine. This action of clonidine was inhibited in a concentration-dependent manner by the alpha-2 adrenoceptor antagonist, yohimbine, and by the alpha-1 adrenoceptor antagonist, prazosin, NANC inhibitory responses were unaffected by clonidine (1 microM). The alpha-1 adrenoceptor agonist, phenylephrine (1 microM), failed to influence responses induced by cholinergic or NANC inhibitory nerve stimulation, acetylcholine or vasoactive intestinal peptide. Furthermore, in tissues treated with propranolol but not subjected to adrenergic neuronal blockade with guanethidine, neurally mediated cholinergic responses were not altered by yohimbine (0.3 microM) treatment. These results indicate that in guinea pig trachea: 1) cholinergic nerves are modulated by presynaptic, prazosin-sensitive inhibitory presynaptic alpha-2 adrenoceptors and 2) NANC inhibitory nerves do not possess presynaptic, modulatory alpha adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

A case-control study of the effectiveness of bicycle safety helmets.

Bicycling accidents cause many serious injuries and, in the United States, about 1300 deaths per year, mainly from head injuries. Safety helmets are widely recommended for cyclists, but convincing evidence of their effectiveness is lacking. Over one year we conducted a case-control study in which the case patients were 235 persons with head injuries received while bicycling, who sought emergency care at one of five hospitals. One control group consisted of 433 persons who received emergency care at the same hospitals for bicycling injuries not involving the head. A second control group consisted of 558 members of a large health maintenance organization who had had bicycling accidents during the previous year. Seven percent of the case patients were wearing helmets at the time of their head injuries, as compared with 24 percent of the emergency room controls and 23 percent of the second control group. Of the 99 cyclists with serious brain injury only 4 percent wore helmets. In regression analyses to control for age, sex, income, education, cycling experience, and the severity of the accident, we found that riders with helmets had an 85 percent reduction in their risk of head injury (odds ratio, 0.15; 95 percent confidence interval, 0.07 to 0.29) and an 88 percent reduction in their risk of brain injury (odds ratio, 0.12; 95 percent confidence interval, 0.04 to 0.40). We conclude that bicycle safety helmets are highly effective in preventing head injury. Helmets are particularly important for children, since they suffer the majority of serious head injuries from bicycling accidents.

Accidents, Traffic↗