bluuebunny/crossref_metadata_2025 huggingface dataset:
The 2001 Veylien Henderson Award of the Society of Toxicology of Canada. Positive and negative transcriptional regulation of cytochromes P450 by polycyclic aromatic hydrocarbons
Authors: Riddick David S , Lee Chunja , Bhathena Anahita , Timsit Yoav E
Published: February 2003

Most responses to aromatic hydrocarbons such as 3-methylcholanthrene (MC) and 2,3,7,8-tetrachlorodibenzo-p-dioxin are mediated by the aromatic hydrocarbon receptor (AHR). The AHR regulates induction of drug-metabolizing enzymes such as cytochrome P450 1A1. However, the expression of several genes of biological significance is decreased by these chemicals. We are examining the mechanisms by which aromatic hydrocarbons suppress constitutive hepatic cytochromes P450, especially the male-specific rat liver cytochrome P450 2C11 (CYP2C11), which is regulated by pulsatile growth hormone (GH) secretion. Aromatic hydrocarbons suppress CYP2C11 via a transcriptional mechanism both in vivo and in cultured hepatocytes, and the AHR appears to be involved; however, studies of proteinDNA interactions and reporter genes driven by the CYP2C11 5'-flanking region have not provided a definitive mechanism for this response. MC attenuates the ability of GH to stimulate hepatic CYP2C11 expression in hypophysectomized (hypx) male rats, and this prompted studies of effects of aromatic hydrocarbons on hepatic GH signaling pathways as a novel aspect of endocrine disruption. Our studies with hypx rats also suggest that the hepatic AHR protein is regulated by a pituitary factor(s). The goal of these molecular mechanistic studies is to improve our understanding of how environmental contaminants modulate the expression of genes coding for xenobiotic- and hormone-metabolizing enzymes.Key words: aromatic hydrocarbons, cytochrome P450, aromatic hydrocarbon receptor, growth hormone, transcriptional regulation.
Isradipine prevents the development of spontaneously occurring cardiac necrosis in cardiomyopathic hamster
Authors: Jacques Danielle , Bkaily Ghassan , Jasmin Gaétan , D'Orléans-Juste Pedro , Chahine Mirna
Published: February 2003

Recent studies on the heart necrotizing process at the early stages of hamster polymyopathy have led us to believe that this hereditary disease derives from an anomalous transmembrane ion flux due to the presence of slow Na+ channels that contribute to intracellular Na+ accumulation which promote intracellular Ca2+ overload via the Ca2+ influx through the Na+Ca2+ exchanger. In the present study, we investigated the potential beneficial effect of chronic treatment with a dual L-type Ca2+ and slow Na+ channel blockers isradipine, on the development of necrosis in myopathic hamster hearts. Young cardiomyopathic (CM) hamsters (CMH) were treated with isradipine (0.1 mg·kg1·day1) and nifedipine (1 mg·kg1·day1) for 4 consecutive weeks. Microscopic assessments were carried out in staged serial paraffin sections of heart ventricles from tissues freshly dissected at autopsy. In comparison with control nontreated hearts, which exhibited numerous necrotic calcific foci, myolytic lesions, and dilated right ventricle, isradipine treatment prevented, in a significant manner, all the above spontaneous pathological changes, while nifedipine had no effect. Our present observations provide evidence for the first time that in vivo treatment with a DHP Ca+ channel blocker, isradipine, is cardioprotective against the development of necrosis in hereditary cardiomyopathy in the hamster. It is possible that the protective effect of isradipine in CMH could be largely due to the indirect blockade of Ca2+ influx through the Na+Ca2+ exchanger as well as to possible direct blockade of Ca2+ influx through the T-type Ca2+ channel.Key words: isradipine, cardioprotection, hamster cardiomyopathy, slow Na+ channel.
Increased endothelin-1 and endothelin receptor expression in myocytes of ischemic and reperfused rat hearts and ventricular myocytes exposed to ischemic conditions and its inhibition by nitric oxide generation
Authors: Gan Xiaohong Tracey , Chakrabarti Subrata , Karmazyn Morris
Published: February 2003

Endothelin-1 (ET-1) and nitric oxide (NO) exert opposite effects in the cardiovascular system, and there is evidence that the NO counters the potential deleterious effects of ET-1. We investigated whether NO affects the increased mRNA expression of ET-1 and endothelin receptors induced by (i) 30 min of ischemia with or without 30 min reperfusion in myocytes from isolated rat hearts or (ii) ischemic conditions (acidosis or hypoxia) in cultured rat neonatal ventricular myocytes. Ischemia with or without reperfusion produced more than a twofold increase in mRNA expression of ET-1 as well as the ETAand ETBreceptor (P < 0.05), although these effects were completely blocked by the NO donor 3-morpholinosydnonimine (SIN-1; 1 μM). To assess the possible factors regulating ET expression, myocytes were exposed to acidosis (pH 6.86.2) or to hypoxic conditions in an anaerobic chamber for 24 h in the presence or absence of SIN-1. At all acidic pHs, ET-1 and ETAreceptor mRNA expression was significantly (P < 0.05) elevated approximately threefold, although the magnitude of elevation was independent of the degree of acidosis. These effects were completely prevented by SIN-1. ETBreceptor expression was unaffected by acidosis. Hypoxia increased ET-1 as well as ETAand ETBreceptor expression threefold (P < 0.05), although this was unaffected by SIN-1. Our results demonstrate that myocardial ischemia and reperfusion upregulate the ET system, which is inhibited by NO. Although increased expression of the ET system can be mimicked by both acidosis and hypoxia, only the effects of the former are NO sensitive. NO may serve an endogenous inhibitory factor which regulates the expression of the ET system under pathological conditions.Key words: ET-1, ET receptors, NO, neonatal rat ventricular myocytes, hypoxia, acidosis.
The fuzzy structure of populations
Authors: Schaefer James A , Wilson Chris C
Published: February 2003

The human perception of biological organization has profound implications for the study, management, and conservation of living things. Traditional methods of classification, which imply all-or-nothing group membership, are inconsistent with the modern synthesis, which stresses variability and unique individuals. We propose that fuzzy classification, which allows fractional membership in multiple clusters, can more realistically denote many forms of biological organization, such as populations. We used fuzzy clustering to depict the ambiguous structure of a migratory caribou (Rangifer tarandus) herd, based on affinities in space use, and walleye (Stizostedion vitreum) stocks, based on genetic dissimilarities among multilocus genotypes. In both cases, fuzzy memberships conveyed the degree of uncertainty of belonging while resolving cluster memberships for unambiguous and problematic individuals. Vagueness implies that borderline group identity cannot be remedied with more resolving power. Fuzzy classification is more in tune with the empirical and philosophical foundations of our discipline and can reconcile our need to classify with an inherently vague biological world.
Ranging and association patterns of paired and unpaired adult male Atlantic bottlenose dolphins, Tursiops truncatus, in Sarasota, Florida, provide no evidence for alternative male strategies
Authors: Owen Edward C.G , Wells Randall S , Hofmann Sue
Published: February 2003

Previous studies of Atlantic bottlenose dolphin, Tursiops truncatus, social structure near Sarasota, Florida, revealed two distinct patterns of ranging and association among paired and unpaired adult males. We evaluated these patterns using a longer-term dataset to examine whether they represent alternative strategies. Males were categorized as paired or unpaired based on coefficients of association using survey data collected year-round from 1993 to 2000. Longitudinal data also allowed for determination of lifetime pair-bond status, which enabled analysis of the occurrence of alternative strategies. Male associations with other males and with females of differing reproductive states were examined annually and seasonally. No significant differences were found between paired and unpaired males in either spatial or temporal patterns of association with all classes of females. Lagged association analysis shows that males tend to associate with breeding females preferentially well before the breeding season starts, suggesting that they may develop affiliative relationships with females during the nonbreeding period to influence female choice later. Paired and unpaired males differed in ranging patterns as calculated by the fixed kernel method. Paired males had significantly larger overall ranging areas (95% utilization distribution (UD)) and core areas (25% UD) than unpaired males. Although these differences were significant, additional demographic analyses of lifetime probability of pair-bond formation suggest that pair bonding is the norm among adult males and that unpaired males are a transitional stage rather than an alternative strategy.
Infestation intensity and prevalence of an ectosymbiotic midge under variable environmental and host conditions
Authors: Pennuto C M , Wooster-Brown C L , Belisle C A
Published: February 2003

Hostsymbiont theory suggests that the abundance of an obligate symbiont will correlate positively with the density and size of its host. We examined these expectations using an obligate chironomid ectosymbiont  host fishfly (Nanocladius (Plecopteracoluthus) sp. No. 5  Nigronia serricornis) system in 13 streams of southern Maine over 2 years (19961998). In addition, we investigated field conditions and macroinvertebrate-community composition, to search for correlates with symbiont prevalence and mean infestation intensity. Prevalence and infestation intensity were high in both years of the study, but neither infestation intensity nor prevalence was correlated with host population density across sites. Within sites, prevalence increased significantly when host density declined, contrary to our expectation. Symbiont-infestation intensity was not related to host size. No symbiont-population attributes correlated with physicochemical conditions in either sample year but prevalence was positively correlated with infestation intensity. Ectosymbiotic midges exhibited a significant host and attachment-site bias. Collectively, these data suggest that this symbionthost interaction is obligate and stable, but the dynamics in our streams do not support the general expectation of increasing symbiont-population size with either increasing host-population or body size. Intraspecific interactions between symbionts are thought to have a stronger influence on population dynamics than do host populations or abiotic conditions for this ectosymbiotic midge.
Monopolization of food by zebrafish (Danio rerio) increases in risky habitats
Authors: Hamilton Ian M , Dill Lawrence M
Published: February 2003

Dominant zebrafish (Danio rerio) previously have been shown to reduce their monopolization of food when foraging in structurally complex habitats compared with open habitats. Complex habitats may be more difficult to defend but may also be safer. To decouple these effects, we compared aggression and monopolization of food in groups of zebrafish foraging in an open habitat and one with overhead cover, as well as in an open habitat and a complex (vegetated) habitat. Covered and open habitats should have been equally defendable. In our experiments, fish used covered habitats more than open ones, suggesting that the perceived risk of predation was lower in covered habitats. There was no difference in use of vegetated and open habitats, suggesting that these habitats, which should differ in defendability, did not differ in safety. We found that the degree of food monopolization (expressed in the coefficient of variation within groups) at risky feeders was significantly greater in open habitats than in covered, but not vegetated, habitats. We did not find a difference in aggression between habitats. These results indicate that resource monopolization in groups of zebrafish is greater in risky habitats and support the hypothesis that the lower monopolization of food in complex habitats could result from greater safety in those habitats rather than, or in addition to, the reduction in defendability.
Breeding time and sex-specific health status in the barn swallow (Hirundo rustica)
Authors: Pap Péter László
Published: February 2003

Health status has been hypothesized to be an important factor associated with individual reproductive performance in birds. Sex-specific health status of early- and late-breeding barn swallows (Hirundo rustica) was studied during the prelaying and brood-rearing periods to test the prediction that early-arriving birds are in better health status than late-arriving individuals. During prelaying, early breeders (of both sexes) had lower leukocyte counts than late breeders, and males had fewer lymphocytes, heterophils, and total white blood cells than females. Sex differences in health status at arrival disappeared during brood rearing, owing to an increase in leukocytes of early-breeding males and a decrease in leukocytes of late-breeding females. Late-breeding males had a higher plasma lutein concentration than early breeders during brood rearing, and the lutein concentration increased significantly for both sexes between prelaying and brood rearing. T-cell immune response of late-breeding females was stronger than for early breeders. These results are consistent with the prediction that health status of breeding barn swallows affects individual performance in terms of breeding time. Individuals differing in quality experience different costs and benefits of early breeding, and these costs and benefits are sex specific.
Effect of microgravity on the swimming behaviour of larvae of the starfishPisaster ochraceus
Authors: Crawford B J , Jackson D
Published: February 2003

Swimming larvae of the starfish Pisaster ochraceus rotate around their animalvegetal axis every 25 s ( 1230 rpm) and exhibit two patterns of swimming behaviour. They may swim with the animal pole forward in any direction or orient vertically (animal pole upward) and remain relatively stationary. Vertically oriented larvae adjust the pattern of rotation so that they present a larger surface area to gravity (holding behaviour). To determine how gravity is involved in the development and pattern of larval swimming behaviour, Pisaster larvae were raised in the aquatic research facility aboard the NASA space shuttle Endeavour (Mission STS 77). Control larvae raised in 1 g appeared to orient themselves along the gravity vector and to exhibit holding behaviour. Tracks of the larval swimming-pattern studies with a motion-analysis system demonstrated that larvae raised in microgravity swam in randomly oriented straight lines or broad arcs. Some of the tracks exhibited oscillations with a period of 25 s, while others did not. The results suggest that the holding behaviour, which normally serves as a response to gravity, develops despite the absence of gravitational clues. Possible mechanisms that the larvae may use to orient to gravity are discussed.
Patterns of microhabitat use in a sympatric lizard assemblage
Authors: James Sarah E , M'Closkey Robert T
Published: February 2003

The distribution of animals among habitats and microhabitats has frequently been used to examine patterns of niche overlap. We characterized microhabitat differences within an assemblage of four phrynosomatine lizard species (Sceloporus graciosus, Sceloporus undulatus, Urosaurus ornatus, and Uta stansburiana) that are commonly syntopic in the pinyon pine  juniper woodland habitat on the elevated mesas of western Colorado. We censused lizard populations and recorded microhabitat characteristics of areas surrounding capture sites within Colorado National Monument, U.S.A. Discriminant function analysis of microhabitat features extracted two significant roots, explaining 89% of the microhabitat variation observed among species. Planned comparisons of canonical scores revealed two significant microhabitat niche differences. First, the microhabitat niche of U. ornatus was distinguished from those of all the other species by higher perch height and more vertical substrate, indicating this species' arboreality. Second, the microhabitat niche of S. graciosus was distinguished from those of the other species by having more flatland and less rock, indicating the use of more open flat sandy areas within the pinyon pine  juniper woodland by this terrestrial species. Although the observed differences in microhabitat may influence the coexistence of these ecologically similar species, changes in relative abundance of the species over time suggest alternative mechanisms of coexistence.
Response of juvenile rainbow trout to varying concentrations of chemical alarm cue: response thresholds and survival during encounters with predators
Authors: Mirza Reehan S , Chivers Douglas P
Published: February 2003

Prey animals may mediate the intensity of their behavioural responses to predators to reflect their risk of predation. However, in the absence of an overt (observable) behavioural response to a particular predation-risk cue, we need to ask whether or not prey animals are still using the cue to assess predation risk. Behavioural responses that are not readily observable within the time frame of the experiment are considered covert. In this study we exposed juvenile rainbow trout, Oncorhynchus mykiss, to varying concentrations of conspecific chemical alarm cue to determine their observable response threshold. In a subsequent experiment we exposed the trout to alarm-cue concentrations above and below their behavioural-response threshold and allowed them to interact with an unknown predator (northern pike, Esox lucius). Trout exposed to concentrations below the observable response threshold were able to evade the predator equally as well as trout exposed to alarm-cue concentrations above the observable response threshold. This study illustrates the sophistication with which prey animals employ chemosensory risk assessment. We must use caution when relying on overt behavioural responses for assessing whether prey are utilizing specific cues to mediate their risk of predation.
Climate-induced variation in vital rates of an unharvested large-herbivore population
Authors: Garrott Robert A , Eberhardt L Lee , White Patrick J , Rotella Jay
Published: February 2003

Variation in vital rates of an unharvested elk (Cervus elaphus) population was studied using telemetry for 7 consecutive years, 19911998. We found pronounced senescence in survival rates, but no evidence for reproductive senescence. Prime-age females (<10 years old) experienced very high annual survival rates (mean = 0.97, SE = 0.02), with lower survival rates for senescent animals ([Formula: see text]10 years old; mean = 0.79, SE = 0.06). There was evidence that the severity of snowpack conditions had little effect on survival of prime-age animals except during the most extreme winter, while survival of senescent animals was progressively depressed as the severity of snowpack conditions increased. Reproductive rates remained essentially constant, near their biological maxima (mean = 0.91, SE = 0.02). Annual re cruitment was highly variable. Snowpack had a pronounced effect on recruitment (r2 = 0.91), the most severe snowpack conditions resulting in the virtual elimination of a juvenile cohort. Population estimates and recruitment rates obtained during this investigation and historic data collected from 1965 to 1980 support the premise that the population has been maintained in a dynamic equilibrium for at least three decades despite the stochastic effects of climate variation on vital rates. We conclude that the population is resource-limited, with variation about the equilibrium caused primarily by variable recruitment driven by stochastic annual snowpack.
Alien mammals and the trophic position of the lesser grison (Galictis cuja) in Argentinean Patagonia
Authors: Delibes Miguel , Travaini Alejandro , Zapata Sonia C , Palomares Francisco
Published: February 2003

The lesser grison (Galictis cuja), a poorly known mustelid of southern South America, has been described as a catholic feeder living close to water. Consequently, the potential exists for competition with the recently introduced American mink (Mustela vison). Nonetheless, like most ferrets the lesser grison can be a specialized mammal hunter, in which case it could benefit from introduced mammalian prey (the European hare, Lepus europaeus, and European rabbit, Oryctolagus cuniculus). The diet and trophic position of the lesser grison in Argentinean Patagonia are described in order to discuss the potential effects of introduced mammalian species on grison populations. Mammals (mainly native rodents and introduced lagomorphs) occurred in 100% of the feces and represented 95% of the biomass consumed. In one site, European hares and rabbits reached a combined 66% of biomass consumed, whereas in the other site rabbits were scarce or absent and lagomorphs represented 35% of the biomass consumed. We postulate that lesser grison populations in Patagonia have benefited from the introduced lagomorphs. On the other hand, lesser grisons frequently occupied river valleys, but did not rely on aquatic or semiaquatic prey. Hence, hunting-habitat preference segregates this mustelid from the American mink (Mustela vison), which consumes a catholic diet in which aquatic species usually predominate.
Spatial relationships between swift foxes and coyotes in northwestern Texas
Authors: Kamler Jan F , Ballard Warren B , Gilliland Rickey L , Mote Kevin
Published: February 2003

Interspecific competition among canids can result in mortalities and spatial displacement of smaller canids by larger canids. To investigate mortalities and spatial relationships of swift foxes (Vulpes velox) and coyotes (Canis latrans), we captured and radio-tracked both species at Rita Blanca National Grasslands in northwestern Texas. At least 89% of swift fox mortalities were caused by coyotes, resulting in a relatively low annual survival of 0.47 for swift foxes. Annual home ranges of swift foxes occurred near the periphery and outside coyote home ranges, and did not overlap or only slightly overlapped coyote core areas. Thirty-three of 36 known swift fox dens occurred outside coyote core areas. When swift foxes established dens within coyote core areas (n = 3), they were killed by coyotes shortly thereafter. Our data indicated that spatial displacement of swift foxes was not due to behavioral avoidance of coyotes but rather to increased killing of swift foxes within coyote core areas. Most mortalities caused by coyotes occurred in the immediate vicinity of swift fox dens, suggesting that coyotes made an active effort to kill swift foxes.
The source and role of RANTES in interstitial lung disease
Authors: Petrek M , Pantelidis P , Southcott AM , Lympany P , Safranek P , Black CM , Kolek V , Weigl E , du Bois RM
Published: February 2003

The chemokine "regulated on activation, normal T-cell expressed and secreted" (RANTES) is a potent eosinophil and lymphocyte attractant with particular preference for CD45RO+ T-cells and eosinophils. These cells accumulate in the lungs of patients with sarcoidosis and fibrosing alveolitis. The purpose of this study was to determine whether RANTES mediates the inflammatory cell influx in these diffuse lung diseases. Cell types and number of bronchoalveolar cells expressing RANTES protein were investigated by immunocytochemistry using lavage cells obtained from 22 patients and 11 control subjects. Subsequently, RANTES messenger ribonucleic acid (mRNA) was semiquantitated using reverse transcription polymerase chain reaction (RT-PCR) methodology in unseparated lavage cell pellets in 26 patients and 13 control subjects. Cells expressing RANTES mRNA were identified by in situ hybridization. RANTES protein expression in lower respiratory tract (LRT) cells was identified in all study groups. The percentage of RANTES+ lavage cells in sarcoidosis was higher than in controls. RANTES was localized in the cytoplasm, mainly in alveolar macrophages (CD68+ cells) in sarcoidosis, and both in alveolar macrophages and eosinophils in fibrosing alveolitis. The same cell types which expressed RANTES protein expressed RANTES mRNA, as assessed by in situ hybridization. Sarcoidosis patients had higher levels of RANTES mRNA than the other groups. RANTES protein was higher in individuals with abnormal lymphocyte numbers: RANTES protein and mRNA expression was significantly correlated with lavage CD45RO+ lymphocyte numbers. These results indicate that RANTES may mediate T-lymphocyte influx in diffuse lung disease, particularly sarcoidosis. Moreover, they suggest that the cellular source of RANTES is the alveolar macrophage in sarcoidosis, and both macrophages and eosinophils in fibrosing alveolitis.
Allergen reduction measures in houses of allergic asthmatic patients: effects of air-cleaners and allergen-impermeable mattress covers
Authors: van der Heide S , Kauffman HF , Dubois AE , de Monchy JG
Published: February 2003

Recommendations for allergen avoidance or allergen reduction measures play an important part in the treatment of allergic asthmatic patients. The purpose of this study was to test recently developed air-cleaners with respect to their capacity to capture airborne allergen particles and to improve clinical parameters of asthmatic patients sensitized to aeroallergens. Forty five allergic asthmatic patients were studied in a double-blind procedure for 6 months. The patients were divided into three groups of 15 patients. In Group 1, the intervention consisted of the application of active air-cleaners in living-rooms and bedrooms. In Group 2, placebo air-cleaners were used in combination with allergen-impermeable mattress covers. In Group 3, the same intervention was performed as in Group 2 but with active air-cleaners. Allergen levels in mattress and floor dust were measured before, and 3 and 6 months after the interventions. After 6 months, the air-cleaners were dismantled and the filters were analysed for the amount of dust collected and allergen content. Immunological and lung function parameters were measured before, and 3 and 6 months after the interventions. Considerable amounts of airborne dust and allergenic particles were captured in the filters of the air-cleaners. Up to the 18.9 g of dust, 4,513 ng of house dust mite allergen, Der p 1, and 50,000 mU of cat allergen, Fel d 1, (in houses with cats) were collected by air-cleaners in living-rooms. Only in Group 3 (in which both active air-cleaners and mattress covers were used) was a small (less than 1 doubling dose) but statistically significant improvement of provocative concentration of histamine causing a 20% fall in forced expiratory volume in one second (PC20) observed (from 5.96 to 9.02 mg x mL(-1)). The amount of dust and house dust mite allergen collected in the filters was significantly correlated with an improvement of peak flow variation. In combination with other allergen avoidance measures, the examined air-cleaners can contribute to diminished allergen exposure and improvement of airway hyperresponsiveness in asthmatic patients.
Asthma in Greenwich, UK: impact of the disease and current management practices
Authors: Marks GB , Burney PG , Premaratne UN , Simpson J , Webb J
Published: February 2003

A great deal of the care of patients with asthma takes place in general practices. The aim of the present study was to describe the impact of asthma in the community and to identify current asthma self-management practices. A two-part questionnaire survey was conducted in a random sample (23%; n=24,398) of persons aged 16-50 yrs, registered with one of the 41 general practices in Greenwich, London, UK. The two parts were: a screening questionnaire identifying persons with current asthma (defined as waking with shortness of breath in the last 12 months, attack of asthma in the last 12 months, or currently taking treatment for asthma); and an asthma questionnaire (completed by those with asthma) assessing quality of life, frequency of asthma symptoms, possession and use of self-management tools, and action in the event of an exacerbation of asthma. The crude response rate was 51%, but this may be an underestimate due to errors in the sampling frame. The prevalences of wheeze and asthma in the past 12 months were 26% and 14%, respectively. Among asthma patients: 43% reported symptoms occurring three or more times per week, and 20% were woken by asthma symptoms on three or more nights per week; most had asthma with a mild impact on quality of life; 26% used inhaled steroids on most days in the preceding month; 16% had a peak flow meter at home; and 7% had oral steroids available. Of the 44% of subjects with asthma, who could identify an exacerbation of asthma in the preceding 6 months: 19% had used a peak flow meter during the episode; 19% had changed their treatment without first being told to do so by a doctor; and 50% had sought urgent medical help. Smokers used less appropriate asthma management and subjects whose asthma had a severe impact on quality of life used more treatment and peak flow monitoring. In conclusion, the prevalence of asthma among adults in Greenwich, UK, has increased since a similar survey in 1986. Many people have fairly mild asthma and a smaller number have severe disease. Much remains to be done to promote appropriate strategies for self-management of asthma exacerbations.
Users of antiasthma drugs in Iceland: a drug utilization study
Authors: Gislason T , Olafsson O , Sigvaldason A
Published: February 2003

There has been an increasing consensus worldwide on how to treat asthma, and, simultaneously, an increase in the sales of antiasthma drugs. However, little is known about actual drug use, dosage, combinations of drugs, etc., or about the clinical characteristics of patients using these drugs. All individuals with prescriptions for antiasthma drugs, who came to Icelandic pharmacies during March 1994, were invited to participate. By means of questionnaires, the pharmacists recorded the age and gender of the patient, the specialty of the prescribing doctor, as well as the name of the drug, total amount prescribed, and dosage. The patients were asked to answer another questionnaire on their clinical diagnosis, usage of other antiasthma drugs, etc. The pharmacists registered 2,026 individuals, with 2,687 prescriptions: 1,574 for beta2-agonists, 838 for inhaled corticosteroids, 208 for theophylline, 48 for anticholinergic drugs, and 19 for cromoglycates. One thousand, three hundred and fifty one patients answered the questionnaires. The majority (67%) claimed to have asthma, 18% chronic bronchitis, 11% emphysema and 5% other diseases or symptoms. Among those aged > or = 16 yrs with asthma, 93% used beta2-agonists, 62% inhaled corticosteroids, 19% theophylline, and very few used other drugs. The most commonly used combination (57%) was beta2-agonists with inhaled corticosteroids. Thirty one per cent used beta2-agonists as monotherapy, and 5% used only inhaled corticosteroids. Theophylline was used mainly in combination with beta2-agonists and inhaled corticosteroids. In conclusion, our data suggest that two thirds of antiasthma drug users have asthma and that most are treated according to present guidelines. The use of inhaled corticosteroids, however, seems somewhat less than optimal.
Increased hydrogen peroxide and thiobarbituric acid-reactive products in expired breath condensate of asthmatic patients
Authors: Antczak A , Nowak D , Shariati B , Krol M , Piasecka G , Kurmanowska Z
Published: February 2003

Symptoms of bronchial asthma are a manifestation of airway inflammation. Circulatory leucocytes (predominantly eosinophils, mast cells and neutrophils), release inflammatory mediators, including reactive oxygen species, i.e. superoxide anion which is dismutated to hydrogen peroxide (H2O2). Neutrophils from asthmatics generate greater amounts of these species than those of healthy subjects. Some of the H2O2 and thiobarbituric acid-reactive products (TBARs) can evaporate from alveolar lining fluid, and could be expired from the airways of asthmatics. In this study, therefore, we determined whether asthmatic patients exhale more H2O2 and TBARs than healthy subjects. We examined 10 healthy subjects as a control group and 21 asthmatic subjects. In asthmatic subjects, forced expiratory volume in one second (FEV1), was 68+/-9% of predicted value, peak expiratory flow rate (PEFR) was 65+/-8% pred, and bronchial reversibility was 34+/-5% of prebronchodilated FEV1. The mean H2O2 level measured spectrofluorimetrically in the expired breath condensate of asthmatic subjects was 26 fold higher than that in healthy controls (0.26+/-0.29 vs 0.01+/-0.03 nM; p<0.05). The concentration of TBARs in breath condensate was also higher in asthmatic patients compared with nonasthmatics (0.073+/-0.071 vs 0.004+/-0.009 nM; p<0.05). There was a significant correlation between H2O2 level and concentration of TBARs in asthmatic patients (r=0.74; p<0.01). There was also a strong inverse correlation between H2O2 content of all asthmatics and FEV1% pred (r=-0.63; p<0.005) and PEFR% pred (r=-0.52; p<0.05). We conclude that there are elevated levels of hydrogen peroxide and thiobarbituric acid-reactive products in expired breath condensate of asthmatic patients, and that measurement of these substances in the expired breath condensate could be a simple, noninvasive method that could be used as a biochemical marker of airway inflammation.
An evaluation of two aerosol delivery systems for rhDNase
Authors: Shah PL , Scott SF , Geddes DM , Conway S , Watson A , Nazir T , Carr SB , Wallis C , Marriott C , Hodson ME
Published: February 2003

Increasingly, proteins are delivered to the respiratory tract as an aerosol, and clinical efficacy is dependent on optimal delivery of the protein in an intact form. The object of this study was to compare the in vivo and in vitro results of two aerosol delivery systems for the aerosolization of recombinant human deoxyribonuclease I (rhDNase) in patients with cystic fibrosis (CF). Patients with CF who were to be initiated on rhDNase were randomized either to the Hudson nebulizer and Pulmo-Aide compressor or to the Sidestream nebulizer driven by the CR50 air compressor. An in vitro study was performed in six sets of the two aerosol delivery systems. One hundred and seventy three patients were randomized in this open study, where rhDNase was administered for 7 days. Improvements in pulmonary function were observed in both groups following 1 week of therapy with rhDNase. Changes in the Sidestream/CR50 and Hudson/Pulmo-Aide groups, respectively, were: 16 and 11% for forced expiratory volume in one second (p=0.14); 12 and 10% for forced vital capacity (p=0.70); and 14 and 7% for forced expiratory flow at 25-75% of expiration (FEF(25-75)) (p=0.18). A greater proportion of patients in the Sidestream/CR50 group (58%) had a >10% response in FEF(25-75) compared to the Hudson/Pulmo-Aide group (42%; p=0.03). The Sidestream nebulizer had a faster nebulization rate (p<0.05), lower mass median diameter for the aerosol mass produced (p<0.001), higher percentage of particles in the respirable range (p<0.001) and greater respirable output (p<0.005), compared to the Hudson nebulizer. The Sidestream/CR50 combination is a quicker, more efficient system in vitro than the Hudson/Pulmo-Aide combination, whereas the in vivo study only suggested a difference. Clinically, the two systems have similar efficacy.
Evaluation of a self-management plan for chronic obstructive pulmonary disease
Authors: Watson PB , Town GI , Holbrook N , Dwan C , Toop LJ , Drennan CJ
Published: February 2003

We hypothesized that the use of an Action Plan might assist self-management for patients with chronic obstructive pulmonary disease (COPD). A pilot process and randomized, controlled study were undertaken to evaluate an Action Plan that provided advice on management of usual care and exacerbations, together with a booklet on self-management. Fifty six subjects with COPD recruited through general practitioners (GPs) completed the 6 month study, 27 in the control group and 29 in the intervention group. The control group received usual care from their GP, and the intervention group received a booklet and Action Plan from their practice nurse plus a supply of prednisone and antibiotic from their GP. The two groups were demographically similar with a mean age of 68 yrs. The resources were well received by GPs, practice nurses and intervention group subjects. After 6 months, there were no differences in quality of life scores or pulmonary function. There were significant changes in self-management behaviour in the intervention group compared to controls. In response to deteriorating symptoms, 34 versus 7% (p=0.014) initiated prednisone treatment and 44 versus 7% (p=0.002) initiated antibiotics. Subjects in the intervention group readily adopted self-management skills but did not show any difference in quality of life or lung function parameters. A larger, prospective, controlled, clinical trial of this approach is warranted.
Sniff nasal inspiratory pressure in patients with chronic obstructive pulmonary disease
Authors: Uldry C , Janssens JP , de Muralt B , Fitting JW
Published: February 2003

In subjects with normal lung mechanics, inspiratory muscle strength can be reliably and easily assessed by the sniff nasal inspiratory pressure (SNIP), which is the pressure measured in an occluded nostril during a maximal sniff performed through the contralateral nostril. The aim of this study was to assess the validity of the SNIP in patients with chronic obstructive pulmonary disease (COPD), where pressure transmission from alveoli to upper airways is likely to be dampened. Twenty eight patients with COPD were studied (mean forced expiratory volume in one second (FEV1) = 36% of predicted). The SNIP and the sniff oesophageal pressure (sniff Poes) were measured simultaneously during maximal sniffs, and were compared to the maximal inspiratory pressure obtained against an occlusion (MIP). All measurements were performed from functional residual capacity in the sitting position. The ratio SNIP/sniff Poes was 0.80, and did not correlate with the degree of airflow limitation. The ratio MIP/sniff Poes was 0.87, and the ratio SNIP/MIP was 0.97. Inspiratory muscle weakness, as defined by a low sniff Poes, was present in 17 of the 28 patients. A false diagnosis of weakness was made in eight patients when MIP was considered alone, in four when SNIP was considered alone, and in only three patients when MIP and SNIP were combined. We conclude that both the sniff nasal inspiratory pressure and the maximal inspiratory pressure moderately underestimate sniff oesophageal pressure in chronic obstructive pulmonary disease. Although suboptimal in this condition, the sniff nasal inspiratory pressure appears useful to complement the maximal inspiratory pressure for assessing inspiratory muscle strength in patients with chronic obstructive pulmonary disease.
Vital capacities in acute and chronic airway obstruction: dependence on flow and volume histories
Authors: Brusasco V , Pellegrino R , Rodarte
Published: February 2003

The aim of this study was to investigate whether measurements of vital capacity (VC) are affected by the direction of the manoeuvre (inspiratory vs expiratory) and by the rate of expiratory flow. The study was performed on 25 individuals with chronic airway obstruction (CAO) and a forced expiratory volume in one second (FEV1) (expressed in standardized residuals (SR)) of -2.0+/-1.4 SD (CAO group), and 10 asthmatic subjects with methacholine (MCh)-induced bronchoconstriction (FEV1 -23+/-1.02 SR) (MCh group). VCs were measured during fast inspiration following both slow (FIVCse) and forced (FIVCfe) expiration from end-tidal inspiration to residual volume (RV), and during slow (EVC) or forced (FVC) expiration from total lung capacity (TLC). In the CAO group, FVC was the smallest volume (3.75+/-1.03 L) and significantly different from the other three estimates of VC; FIVCse (4.03+/-0.91 L) was the largest volume and significantly different from FVC and FIVCfe (3.83+/-0.98 L). In the MCh group, FVC (4.16+/-0.94 L) and EVC (4.19+/-0.89 L) were the largest volumes, although only the difference between FVC and FIVCfe (3.76+/-0.81 L) reached statistical significance. These data suggest that both flow and volume histories contribute to decreased vital capacities during bronchoconstriction. However, whereas increasing expiratory flow always tends to decrease vital capacity, the volume history of full inflation has different effects in chronic and acute bronchoconstriction, probably due to different effects on airway calibre. These results stress the importance of using standardized manoeuvres in order to obtain comparable values of vital capacity.
In vitro comparison of the amount of salbutamol available for inhalation from different formulations used with different spacer devices
Authors: Barry PW , O'Callaghan C
Published: February 2003

Metered-dose inhalers (MDIs) are currently being reformulated to contain hydrofluoroalkanes (HFAs), which do not damage the Earth's ozone layer. As different formulations of inhaled drugs may behave differently when used with spacer devices, we wished to determine the amount of salbutamol available for inhalation from a conventional metered-dose inhaler (Ventolin) and a new HFA-containing formulation (Airomir), when used with two different spacers. A glass multistage liquid impinger was used to determine the amount of salbutamol delivered from the inhalers used with the Aerochamber and the Nebuhaler spacer devices. High speed video-recordings of inhaler actuation into air were made, and the speed of the aerosol and the aerosol cloud volume were measured. More salbutamol in small particles (<5 microm) was delivered from the Airomir MDI than the Ventolin MDI, when used with the Aerochamber (40.4 (95% confidence interval (95% CI) 31.2-49.6) versus 19.5 (19.0-20.0) microg) and the Nebuhaler (42.1 (36.3-47.9) versus 24.6 (23.3-25.8) microg). The aerosol cloud from the Airomir MDI was slower than the Ventolin aerosol, and 60 ms after actuation had travelled 186 mm, whereas the Ventolin aerosol had travelled 320 mm. At the same time, the Airomir aerosol occupied a smaller volume than the Ventolin MDI (251 (213-288) versus 695 (608-782) cm3). The hydrofluoroalkane formulation delivers more salbutamol than the conventional formulation when used either with the Aerochamber or Nebuhaler spacer. This may be because less drug is deposited in the spacer from the hydrofluoroalkane formulation, which is emitted from the metered-dose inhaler at a slower speed and occupies a smaller volume than the conventional formulation. The observed difference in drug delivery may be important for patients changing formulations, and in severe asthma, where high doses of salbutamol may be administered through a spacer.
Acute severe asthma: pathophysiology and pathobiology of gas exchange abnormalities
Authors: Rodriguez-Roisin R
Published: February 2003

Acute severe asthma, or "status asthmaticus", is a devastating clinical condition ultimately resulting in life-threatening hypoxaemia. The pivotal intrapulmonary mechanism of this condition is profound ventilation/perfusion (V'A/Q') mismatch, characterized by a predominant bimodal blood flow pattern reflecting a marked deterioration (increase) of the dispersion of pulmonary blood flow. This V'A/Q' profile is consistent with the presence of numerous alveolar units with low V'A/Q' ratios, in which ventilation is markedly reduced, although never abolished, but perfusion is maintained. Further V'A/Q' worsening whilst breathing 100% O2 suggests the presence of an underlying vigorous hypoxic vascular response. Of equal importance, gas exchange disturbances are poorly related to the severity of reduced maximal airflow rates. Inhaled platelet-activating factor (PAF), both in normal individuals and asthmatic patients, results in moderate-to-severe disturbance of V'A/Q' status, a finding that is probably related to altered microvascular permeability within the airway wall. Salbutamol, but not ipratropium bromide, prevented all PAF-induced systemic and lung function abnormalities, possibly because venoconstriction in the bronchial circulation was antagonized. Taken together, these findings support the hypothesis that platelet-activating factor may play a critical role in the pathobiology of severe acute exacerbations of asthma.
Cellular glutathione turnover in vitro, with emphasis on type II pneumocytes
Authors: van Klaveren RJ , Demedts M , Nemery B
Published: February 2003

The most important extracellular antioxidant in the lung is glutathione (GSH). The epithelial lining fluid of normal lungs contains very high concentrations of this tripeptide, about 100 times higher than that found in the extracellular fluid of many other tissues. How these high extracellular GSH levels are established and the mechanisms for increases (e.g. smokers) or decreases (e.g. lung fibrosis) are still unknown, but more insight into the regulation of GSH turnover in type II pneumocytes has recently become available. The purpose of this review is to give an overview of the literature concerning cellular GSH turnover for different cell types in vitro, with an emphasis on alveolar type II epithelial cells. The main messages of this review are that: 1) GSH is, in fact, an important vehicle for stabilizing, detoxifying and transferring cysteine; 2) cysteine is the rate-limiting substrate for GSH synthesis, especially under conditions of oxidative stress; 3) various transport systems exist for the uptake of the constituents of GSH, of which gamma-glutamyltransferase appears to be important; 4) intracellular GSH levels of the type II cells are governed by different factors, including, probably, the extracellular redox state; and 5) a more reduced extracellular redox state appears to favour GSH efflux, whilst an oxidized state leads to retention of GSH inside the cell. These concepts should lead to reconsideration of some of the conventional approaches to increasing intracellular glutathione levels.
Psychiatry and the media
Authors: Byrne Peter
Published: February 2003

Aspects of print, broadcast, film and ‘new media’ are related to their interactions with psychiatry. Frequent representations of mental health issues are paralleled by the adoption of psychological theories into media studies. Key areas are covered where psychiatric items diverge from other medical specialities, such as the depiction of suicide, the dominance of ‘human interest’ stories and negative representation of people with mental illness. Although the language of mental disorders is important, the power of the image needs to be examined. Media items also have implications for public mental health (children as vulnerable viewers) and the clinical practice of psychiatry that are not uniformly negative. Television has limitations and clinicians are encouraged to participate in radio and other media. Resources and practical advice for media contact are provided.
Intoxication and legal defences
Authors: Haque Quazi , Cumming Ian
Published: February 2003

Intoxication with alcohol and drugs is commonly associated with criminal offending. The relationship between intoxication and criminal culpability is complex and may be of psychiatric relevance, especially if a mental condition legal defence is being considered. This article outlines the legal issues (such as they apply in England and Wales) of which psychiatrists should be aware when preparing medico-legal opinions about mentally disordered offenders.