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Biomedical subjects

D C Thompson

Publications and source records attributed to D C Thompson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Fit of bicycle safety helmets and risk of head injuries in children.

BACKGROUND: Although bicycle helmets are effective in preventing head and brain injury, some helmeted individuals nevertheless sustain head injury. One of the possible reasons may be poor fit of the helmet on the head. This study was undertaken to examine the relationship between helmet fit and risk of injury. METHODS: 1718 individuals who were helmeted riders in a crash were queried on helmet fit and position. A sample of 28 children 2-14 years of age who sustained a head injury while wearing a bicycle helmet and 98 helmeted individuals of the same age treated in the same hospital emergency departments for injuries other than to the head, underwent anthropometric measurements of helmet fit. Measurements were made of the child's head, the helmet, and on a cast made of the child's head. RESULTS: Individuals whose helmets were reported to fit poorly had a 1.96-fold increased risk of head injury compared with those whose helmets fit well. Children with head injuries had helmets which were significantly wider than their heads compared with children without head injuries. Helmet fit was poorer among males and among younger children. CONCLUSIONS: Poor fit of helmets may be associated with an increased risk of head injury in children, especially in males. Helmets may not be designed to provide optimal protection.

Adolescent↗
PubMed1998

Synthesis and structure-activity relationships of potent and orally active 5-HT4 receptor antagonists: indazole and benzimidazolone derivatives.

A series of indole-3-carboxamides, indazole-3-carboxamides, and benzimidazolone-3-carboxamides was synthesized and evaluated for antagonist affinity at the 5-HT4 receptor in the rat esophagus. The endo-3-tropanamine derivatives in the indazole and benzimidazolone series possessed greater 5-HT4 receptor affinity than the corresponding indole analogues. 5-HT4 receptor antagonist affinity was further increased by alkylation at N-1 of the aromatic heterocycle. In a series of 1-isopropylindazole-3-carboxamides, replacement of the bicyclic tropane ring system with the monocyclic piperidine ring system or an acyclic aminoalkylene chain led to potent 5-HT4 receptor antagonists. In particular, those systems in which the basic amine was substituted with groups capable of forming hydrogen bonds showed increased 5-HT4 receptor antagonist activity. While some of these compounds displayed high affinity for other neurotransmitter receptors (in particular, 5-HT3, alpha1, and 5-HT2A receptors), as the conformational flexibility of the amine moiety increased, the selectivity for the 5-HT4 receptor also increased. From this series of compounds, we identified LY353433 (1-(1-methylethyl)-N-[2-[4-[(tricyclo[3.3.1.1(3, 7)]dec-1-ylcarbonyl)amino]-1-piperidinyl]ethyl]-1H-indazole-3- carboxamide) as a potent and selective 5-HT4 receptor antagonist with clinically suitable pharmacodynamics.

Adamantane↗
PubMed1998

Comparative toxicity of eugenol and its quinone methide metabolite in cultured liver cells using kinetic fluorescence bioassays.

Comparative kinetic analyses of the mechanisms of toxicity of the alkylphenol eugenol and its putative toxic metabolite (quinone methide, EQM) were carried out in cultured rat liver cells (Clone 9, ATCC) using a variety of vital fluorescence bioassays with a Meridian Ultima laser cytometer. Parameters monitored included intracellular GSH and calcium levels ([Ca2+]i), mitochondrial and plasma membrane potentials (MMP and PMP), intracellular pH, reactive oxygen species (ROS) generation, and gap junction-mediated intercellular communication (GJIC). Cells were exposed to various concentrations of test compounds (1 to 1000 microM) and all parameters monitored directly after addition at 15 s intervals for at least 10 min. Eugenol depleted intracellular GSH, inhibited GJIC and generation of ROS, and had a modest effect on MMP at concentrations of 10 to 100 microM. At high concentrations (1000 microM), eugenol also affected [Ca2+]i, PMP, and pH. Effects of EQM were seen at lower concentrations (1 to 10 microM). The earliest and most potent effects of either eugenol or EQM were seen on GSH levels and GJIC. Coadministration of glutathione ethyl ester enhanced intracellular GSH levels by almost 100% and completely protected cells from cell death caused by eugenol and EQM. These results suggest that eugenol mediates its hepatotoxic effects primarily through depletion of cytoprotective thiols and interference in thiol-dependent processes such as GJIC. Furthermore, our results support the hypothesis that the toxic effects of eugenol are mediated through its quinone methide metabolite.

Animals↗
PubMed1998

Prevention of bicycle-related injuries: helmets, education, and legislation.

Efforts to reduce the toll of bicycle-related head injuries illustrate how the basic public health principles of surveillance, epidemiologic study, intervention, and evaluation can have a substantial impact on an injury problem, using a variety of injury-prevention strategies. Head injuries are the leading cause of serious morbidity and mortality from bicycle crashes. Helmets have been shown to reduce bicycle-related head injuries for cyclists of all ages involved in all types of crashes including those with motor vehicles. Helmet use has been promoted using educational campaigns, helmet subsidies, and legislation. Careful evaluation of these strategies has shown that these interventions increase helmet use and decrease the incidence of bicycle injuries. The model developed for the prevention of bicycle injuries is widely applicable to other injury problems.

Age Factors↗
PubMed1998

Cytokine-induced nitric oxide formation in normal but not in neoplastic murine lung epithelial cell lines.

Cytomix, a mixture of interferon-gamma, tumor necrosis factor-alpha, and interleukin-1beta, induces nitric oxide (NO) production in lung epithelial cell lines. It is not known whether neoplastic transformation alters a cell's ability to form NO in response to cytokines. The present study investigated NO formation in two murine lines of immortalized "normal" (nontumorigenic) lung epithelial cells of alveolar type II origin, E10 and C10, and their sibling spontaneous transformants, E9 and A5. Nontumorigenic cells elaborated much more NO after cytomix exposure than did their tumorigenic counterparts. NO production was prevented by inhibiting protein synthesis and NO synthase and attenuated by dexamethasone. Northern and Western blot analyses of inducible NO synthase (iNOS) demonstrated cytomix-induced induction of iNOS only in nontumorigenic cells. The deficiency in NO production in tumorigenic cells was not associated with reduced iNOS mRNA stability or with differences in cytomix-induced nuclear factor-kappaB activation. Although cytomix caused a greater production of NO in E10 cells than in E9 cells, the same treatment induced equivalent proliferation in both cell lines. These results indicate a specific deficiency in cytokine-induced NO synthesis in transformed murine lung epithelial cells relative to their normal progenitor cells and provide a model for investigating iNOS regulation.

Animals↗
PubMed1998

Cycle helmets and the prevention of injuries. Recommendations for competitive sport.

The scientific evidence that bicycle helmets protect against head, brain and facial injuries has been well established by 5 well designed case-control studies. Additional evidence of helmet effectiveness has been provided from time series studies in Australia and the US. Bicycle helmets of all types that meet various national and international standards provide substantial protection for cyclists of all ages who are involved in a bicycle crash. This protection extends to crashes from a variety of causes (such as falls and collisions with fixed and moving objects) and includes crashes involving motor vehicles. Helmet use reduces the risk of head injury by 85%, brain injury by 88% and severe brain injury by at least 75%. Helmets should be worn by all riders whether the cyclist is a recreational rider or a serious competitor engaged in training or race competition. The International Cycling Federation (ICF) should make the use of helmets compulsory in all sanctioned races.

Accidental Falls↗
PubMed1998

A training program to improve domestic violence identification and management in primary care: preliminary results.

Domestic violence as encountered in day-to-day practice is greatly underidentified. It is estimated that only 3% of cases are presently being identified, and practitioners are uncertain of what to do if a case is discovered. In this paper, a training program to improve identification and management of domestic violence (DV) in primary care and the providers' responses to the program are described. A multimodal training program was undertaken to demonstrate and practice the incorporation of didactic content into practice for the health care teams. Two medical centers from a large staff-model HMO were chosen at random from five volunteering for training. The entire adult health care medical center teams, including physicians, physician assistants, RNs, LPNs, medical assistants, and receptionists, were the recipients of the training. Assessment of provider valuation of the components of the training program was performed by administering a standardized 5-point Likert-scaled questionnaire 9 months after the training. This time interval was chosen because we were interested in lasting program effects. Core didactic content, such as the epidemiology of DV, identification and management of victims and batterers, and legal issues, was highly rated. Delivery of the content through role-playing, start-stop videos and presentations by former victims received lesser but solid support. Follow-up assessment 9 months post training demonstrates solid support for many components of the program: highest for specific information content areas, but strong for techniques and processes. The training program appears to be a promising method to improve provider skills in DV management.

Adult↗
PubMed1998

Differential susceptibility of tracheal contraction to nonadrenergic noncholinergic relaxation.

Studies of nonadrenergic noncholinergic inhibitory (NANCi) nerve-induced relaxations routinely examine relaxations in airway tissue in which tone has been established. Little is known about the ability of NANCi nerve stimulation to prevent airway smooth muscle contraction. The present study compares the capacity of NANCi nerve stimulation to prevent or reverse airway smooth muscle contraction. NANCi nerves in the trachea from ovalbumin-sensitized guinea pigs were subjected to electrical field stimulation (EFS, 10 Hz, 0.3 ms, 10 V, 35 min) initiated before or after induction of tone with antigen or histamine. In tissues precontracted with histamine or antigen, EFS elicited a rapid relaxation which peaked within the first 5 min and stabilized by 20 to 35 min. The peak relaxation was smaller in tissues precontracted with antigen, an effect that was not prevented by tissue treatment with a nitric oxide synthase inhibitor. In contrast, the stabilized level of NANCi relaxation did not differ between histamine- or antigen-contracted tissues. Activation of NANCi nerves prior to induction of tone also resulted in inhibition of the contractile actions of histamine and antigen. However, the stabilized level of tone induced by a contractile agonist added after initiation of EFS was greater than the stabilized tone caused by EFS in tissues already contracted with the same agonist. Relaxations elicited by S-nitrosoglutathione were reduced in antigen-precontracted tissues whereas vasoactive intestinal peptide-induced relaxant responses were similar in antigen- and histamine-precontracted tissues. Results of this study suggest that NANCi nerve activation is more effective at relaxing established airway smooth muscle tone than at preventing airway smooth muscle contraction. Further, the results suggest that the difference in NANCi activity in antigen-precontracted tissues cannot be ascribed solely to reductions in the nitric oxide-dependent component of the response.

Animals↗
PubMed1997

Damage to bicycle helmets involved with crashes.

The objective was to evaluate the relationship between helmet damage and head injuries in helmeted bicyclists in a sub-study of a large case-control study of bicycle injuries and helmet effectiveness. The setting consisted of seven hospital emergency departments in Seattle, WA. Hospitalized patients and medical examiners cases were included. The participants in the study were helmeted bicyclists who suffered a head injury or who damaged or hit their helmet in a crash. The Snell Memorial Foundation laboratory evaluated the helmets, blinded to crash circumstance and injury diagnosis. Damage was scored on a five-point scale (0 = none to 4 = destroyed). The damage location for each helmet was coded into regions (six longitudinal and three latitudinal) and mapped onto a three-dimensional CAD (computer-aided design) model of a helmet. The same procedure was also followed for injury location, which was mapped onto a three-dimensional ISO (International Organization for Standardization) headform for visualization of head-injury distribution. 785 helmeted subjects met the criteria for inclusion in the sub-study, and 527 helmets were purchased and evaluated (67%). 316 (60%) of the helmets had no or minimal damage, and 209 (39.7%) had significant damage (score 2, 3 or 4). Helmet types were 49.7% hard shell, 34.2% thin shell and 16.1% no shell. The risk of head and brain injury increased if the helmet was destroyed: OR = 5.3 (95% CI 2.9, 9.9) and OR = 11.2 (95% CI 3.5, 37.9), respectively. A high proportion of helmet impacts were along the front edge of the helmet, with a preponderance of head injuries in the same region. The large number of impacts to the front rim of the helmet, combined with the substantial number of riders with injuries to the forehead, indicate that some helmets, because of poor fit or wearing style, expose the forehead to injury. In addition, the data indicate that for a small proportion of injuries, the energy to the helmet may exceed design limits.

Accidents, Traffic↗
PubMed1997

Immunochemical visualization and identification of rat liver proteins adducted by 2,6-di-tert-butyl-4-methylphenol (BHT).

Several alkylphenols (e.g., 2,6-di-tert-butyl-4-methylphenol, BHT) form reactive quinone methide intermediates (e.g., 2,6-di-tert-butyl-4-methylene-2,5-cyclohexadienone, BHT-QM) upon oxidation by cellular enzymes. In order to pursue the role of protein alkylation in alkylphenol toxicity, we used an immunochemical approach to identify protein targets alkylated by BHT. Synthetic BHT-N-acetylcysteine (BHT-NAC) was coupled to keyhole limpet hemocyanin and used as an antigen from which polyclonal antibodies were raised in New Zealand white rabbits. Rabbit serum contained an antibody which was highly specific for BHT-NAC, as determined by competitive ELISA. The BHT antibody was used as a probe to look for the presence of BHT-protein adducts in in vitro incubations with rat liver microsomes or tissue slices and also in vivo in liver tissue from male Sprague-Dawley rats exposed to BHT. Western blotting of protein gels revealed BHT-dependent protein alkylation over a wide molecular weight range. Prominent recurrent bands were observed at approximately 34.5, 52, 64.5, 74, and 97 kDa. Detection of adducts was inhibited in microsomal incubations by cytochrome P450 inhibitors, deuterated BHT, and the omission of NADPH. Similar protein alkylation patterns were observed in rat liver microsomes exposed to synthetically prepared BHT-QM as in the enzyme-mediated incubations. In rats gavaged with up to 1000 mg/kg BHT, the amount of protein alkylation observed was maximal at 24 h postdosing and was dose-dependent. Two alkylated proteins were isolated and identified by N-terminal sequencing: a mitochondrial beta-oxidation enzyme, enoyl-CoA hydratase, and a plasma membrane/cytoskeletal linker protein from the ezrin/moesin/radixin family.

Alkylation↗
PubMed1997

Bike speed measurements in a recreational population: validity of self reported speed.

OBJECTIVE: Speed at the time of a bicycle crash is an important determinant of the amount of energy transmitted. Controlling for speed is thus important in the evaluation of outcomes and effectiveness of intervention strategies. This study was conducted to evaluate the accuracy of self reported speed in a population of recreational cyclists. METHODS: Children's and adults' bicycle speeds were measured with a radar gun as they rode along a closed road at weekend recreational events. Cyclists were then stopped and asked to estimate their speed. Measured speed, cyclist's estimate of their speed, age, and sex were documented. Parents were also asked to estimate their child's speed. RESULTS: One hundred and fifty two cyclists from 4 to 80 years of age participated. Seventy per cent were children 13 years of age or younger. The mean (SD) speed of this group was 8.9 (2.5) mph. Cyclists age 14 and older were traveling at a mean speed of 9.7 (2.87) mph. Estimated speeds were significantly higher than measured speeds for this older group, but there was no significant difference between mean measured and estimated speeds for the younger riders. There was also no significant difference between measured and estimated speed for males and females. Parents estimated their child's speed quite accurately. CONCLUSIONS: Self reported speeds for children were in close agreement with measured speeds and, thus, are sufficiently accurate to be a useful measure of crash severity in evaluating helmet effectiveness.

Adolescent↗
PubMed1997

Epidemiology of bicycle injuries and risk factors for serious injury.

OBJECTIVE: To determine the risk factors for serious injury to bicyclists, aside from helmet use. DESIGN: Prospective case-control study. SETTING: Seven Seattle area hospital emergency departments and two county medical examiner's offices. PATIENTS: Individuals treated in the emergency department or dying from bicycle related injuries. MEASUREMENTS: Information collected from injured bicyclists or their parents by questionnaire on circumstances of the crash; abstract of medical records for injury data. Serious injury defined as an injury severity score > 8. ANALYSIS: Odd ratios computed using the maximum likelihood method, and adjusted using unconditional logistic regression. RESULTS: There were 3854 injured cyclists in the three year period; 3390 (88%) completed questionnaires were returned 51% wore helmets at the time of crash. Only 22.3% of patients had head injuries and 34% had facial injuries. Risk of serious injury was increased by collision with a motor vehicle (odds ratio (OR) = 4.6), self reported speed > 15 mph (OR = 1.2), young age (< 6 years), and age > 39 years (OR = 2.1 and 2.2 respectively, compared with adults 20-39 years). Risk for serious injury was not affected by helmet use (OR = 0.9). Risk of neck injury was increased in those struck by motor vehicles (OR = 4.0), hospitalized for any injury (OR = 2.0), and those who died (OR = 15.1), but neck injury was not affected by helmet use. CONCLUSIONS: Prevention of serious bicycle injuries cannot be accomplished through helmet use alone, and may require separation of cyclists from motor vehicles, and delaying cycling until children are developmentally ready.

Adolescent↗
PubMed1997

Injuries involving off-road cycling.

BACKGROUND: Data on injuries due to off-road bicycling are scarce, but do indicate that injuries in this sport are frequent. We examined the pattern of injuries to off-road riders as part of a larger study of bicycle injuries and helmet use. METHODS: We undertook a prospective study of bicycle-related injuries identified at seven emergency departments in Seattle, Washington, between March 1992 and August 1994. Hospitalized patients and medical examiners' cases were included. Detailed questionnaires and abstraction of all medical records provided information on crash and rider characteristics and injury type and severity. RESULTS: A total of 3390 injured riders participated, representing an 88% response rate. Of all injured cyclists, 127 (3.7%) were injured riding "off road." Seventy-three percent of off-road cyclists were 20 to 39 years of age, and 86.6% were male. Helmet use was 80.3% for off-road cyclists as compared with 49.5% for other cyclists. The number of head and face injuries for the off-road cyclists was only 40% of the number incurred by other cyclists. Four percent of off-road cyclists had severe injuries (injury Severity Score > 8), and 6.3% were hospitalized, compared with 6.8% and 9.4%, respectively, of other cyclists. CONCLUSIONS: The majority of off-road bicycling injuries are minor. Off-road cyclists are less likely to have head and face injuries than other cyclists and are more likely to wear helmets.

Accidents↗
PubMed1997

Absence of tachykinin involvement in leukotriene D4 and antigen-induced contraction of guinea pig isolated bronchus.

In guinea pig airways, contractions induced by leukotriene D4 or antigen are thought to be mediated primarily by an action of the agonist or of released mast cell-derived mediators directly on the airway smooth muscle cell. An indirect contractile action mediated by endogenous tachykinins also has been described for both of these stimuli. The present study evaluated the contribution of endogenous tachykinins to ovalbumin- and leukotriene D4-induced contractions in the guinea pig bronchus by modulating the concentrations of tachykinins within the tissues and by using neurokinin receptor antagonists. Acute depletion of tachykinins with capsaicin had no effect on responses elicited by either stimulus. Similarly, tetrodotoxin treatment failed to influence leukotriene D4-induced contractions. Inhibitors of neutral endopeptidase (thiorphan) and angiotensin-converting enzyme (lisinopril) enhanced neurally mediated tachykininergic responses and potentiated leukotriene D4. The latter effect persisted in the presence of tetrodotoxin or the neurokinin antagonists CP99994 and SR48968 and in tissues treated acutely with capsaicin. The potentiation was absent, however, from bronchi incubated with L-cysteine. Ovalbumin-induced contractions were unaltered by inhibition of neutral endopeptidase and angiotensin-converting enzyme. These observations suggest that tachykinins are not involved in mediation of leukotriene D4- or antigen-induced contractions of the guinea pig bronchus. The ability of protease inhibitors to potentiate leukotriene D4 but not antigen-induced responses is therefore ascribed to inhibition of bioinactivation of leukotriene D4 to leukotriene E4.

Animals↗
PubMed1996

Effectiveness of bicycle safety helmets in preventing head injuries. A case-control study.

OBJECTIVES: To examine the protective effectiveness of bicycle helmets in 4 different age groups of bicyclists, in crashes involving motor vehicles, and by helmet type and certification standards. RESEARCH DESIGN: Prospective case-control study SETTING: Emergency departments (EDs) in 7 Seattle, Wash, area hospitals between March 1, 1992, and August 31, 1994. PARTICIPANTS: Case subjects were all bicyclists treated in EDs for head injuries, all who were hospitalized, and all who died at the scene. Control subjects were bicyclists treated for nonhead injuries. MAIN RESULTS: There were 3390 injured bicyclists in the study; 29% of cases and 56% of controls were helmeted. Risk of head injury in helmeted vs unhelmeted cyclists adjusted for age and motor vehicle involvement indicate a protective effect of 69% to 74% for helmets for 3 different categories of head injury: any head injury (odds ratio [OR], 0.31; 95% confidence interval [CI], 0.26-0.37), brain injury (OR, 0.35; 95% CI, 0.25-0.48), or severe brain injury (OR, 0.26; 95% CI, 0.14-0.48). Adjusted ORs for each of 4 age groups (<6 y, 6-12 y, 13-19 y, and > or = 20 years) indicate similar levels of helmet protection by age (OR range, 0.27-0.40). Helmets were equally effective in crashes involving motor vehicles (OR, 0.31; 95% CI, 0.20-0.48) and those not involving motor vehicles (OR, 0.32; 95% CI, 0.20-0.39). There was no effect modification by age or motor vehicle involvement (P=.7 and P=.3). No significant differences were found for the protective effect of hard-shell, thin-shell, or no-shell helmets (P=.5). CONCLUSIONS: Bicycle helmets, regardless of type, provide substantial protection against head injuries for cyclists of all ages involved in crashes, including crashes involving motor vehicles.

Accidents, Traffic↗
PubMed1996

Effectiveness of bicycle safety helmets in preventing serious facial injury.

OBJECTIVE: To assess the effectiveness of helmets in preventing facial injuries. DESIGN: Case-control study between March 1, 1992, and August 31, 1994. SETTING: Seven Seattle, Wash, area hospitals including the regional trauma center and a large staff-model health maintenance organization. PATIENTS: Cases were patients with serious facial injury, ie, fractures or lacerations; controls were patients who had injuries other than facial. Minor facial injuries were excluded to avoid ascertainment bias in those seeking care for serious injuries to other areas. RESULTS: Serious facial injuries occurred to 700 (20.7%) patients. Helmets were used by 47% of cases and 57% of controls. After adjusting for age, sex, speed, and surface, we found that helmets reduced the risk of injury to the upper face (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.26-0.49) and middle face (OR, 0.35; 95% CI, 0.24-0.50) but had no significant effect on serious injury to the lower face (OR, 0.88; 95% CI, 0.72-1.07). CONCLUSIONS: Bicycle helmets offer substantial protection for the upper and mid face in addition to their known protection against head injuries. Helmets do not appear to offer any protection for the lower face.

Adolescent↗