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Biomedical subjects

J Coughlan

Publications and source records attributed to J Coughlan.

At least 19 recordsLinked to original sources

Investigating the possible role of benthic macroinvertebrates and zooplankton in the life cycle of the haplosporidian Bonamia ostreae.

Bonamia ostreae is a protistan parasite of the European flat oyster, Ostrea edulis. Though direct transmission of the parasite can occur between oysters, it is unclear if this represents the complete life cycle of the parasite, and the role of a secondary or intermediate host or carrier species cannot be ruled out. In this preliminary study, benthic macroinvertebrates and zooplankton from a B. ostreae-endemic area were screened for the presence of parasite DNA, using polymerase chain reaction (PCR). Eight benthic macroinvertebrates and nineteen grouped zooplankton samples gave positive results. Certain species, found positive for the parasite DNA, were then used in laboratory transmission trials, to investigate if they could infect naïve oysters. Transmission of B. ostreae was effected to two naïve oysters cohabiting with the brittle star, Ophiothrix fragilis.

Animals↗

Limited (information only) patient education programs for adults with asthma.

BACKGROUND: A key component of many asthma management guidelines is the recommendation for patient education and regular medical review. A number of controlled trials have been conducted to measure the effectiveness of asthma education programmes. These programmes improve patient knowledge, but their impact on health outcomes is less well established. At its simplest level, education is limited to the transfer of information about asthma, its causes and its treatment. This review focused on the effects of limited asthma education. OBJECTIVES: The objective of this review was to assess the effects of limited (i.e. information only) asthma education on health outcomes in adults with asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and reference lists of articles. SELECTION CRITERIA: Randomised and controlled trials of individual asthma education involving information transfer only in adults over 16 years of age. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for missing information. MAIN RESULTS: Eleven trials were included. They were of variable quality. Limited asthma education did not reduce hospitalisation for asthma (weighted mean difference -0.03 average hospitalisations per person per year, 95% confidence interval -0.09 to 0.03). There was no effect on doctor visits, lung function and medication use. The effects on asthma symptoms were variable. There was no reduction in days lost from normal activity, but perceived asthma symptoms did improve after limited asthma education (odds ratio 0.40, 95% confidence interval 0.18 to 0.86). In one study, limited asthma education was associated with reduced emergency department visits (weighted mean difference -2.76 average visits per person per year, 95% confidence interval -4.34 to 1.18). REVIEWER'S CONCLUSIONS: Use of limited asthma education as it has been practiced does not appear to improve health outcomes in adults with asthma. However the use of information in the emergency department may be effective, but this needs to be confirmed.

Adult↗

Self-management education and regular practitioner review for adults with asthma.

BACKGROUND: A key component of many asthma management guidelines is the recommendation for patient education and regular medical review. A number of controlled trials have been conducted to measure the effectiveness of asthma education programmes. These programmes improve patient knowledge, but their impact on health outcomes is less well established. This review was conducted to examine the strength of evidence supporting Step 6 of the Australian Asthma Management Plan: "Educate and Review Regularly"; to test whether health outcomes are influenced by education and self-management programmes. OBJECTIVES: The objective of this review was to assess the effects of asthma self-management programmes, when coupled with regular health practitioner review, on health outcomes in adults with asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and reference lists of articles. SELECTION CRITERIA: Randomised trials of self-management education in adults over 16 years of age with asthma. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for confirmation. MAIN RESULTS: Twenty-five trials were included. Self-management education was compared with usual care in 22 studies. Self-management education reduced hospitalisations (odds ratio 0.57, 95% confidence interval 0.38 to 0.88); emergency room visits (odds ratio 0.71, 95% confidence interval (0.57 to 0.90); unscheduled visits to the doctor (odds ratio 0.57, 95% confidence interval 0.40 to 0.82); days off work or school (odds ratio 0.55, 95% confidence interval 0.38 to 0. 79); and nocturnal asthma (odds ratio 0.53, 95% confidence interval 0.39 to 0.72). Measures of lung function were little changed. Self-management programmes that involved a written action plan showed a greater reduction in hospitalisation than those that did not (odds ratio 0.35, 95% confidence interval 0.18 to 0.68). People who managed their asthma by self-adjustment of their medications using an individualised written plan had better lung function than those whose medications were adjusted by a doctor. REVIEWER'S CONCLUSIONS: Training in asthma self-management which involves self-monitoring by either peak expiratory flow or symptoms, coupled with regular medical review and a written action plan appears to improve health outcomes for adults with asthma. Training programmes which enable people to adjust their medication using a written action plan appear to be more effective than other forms of asthma self-management.

Adult↗

Long acting beta-agonists versus theophylline for maintenance treatment of asthma.

BACKGROUND: Theophylline and long acting beta2-agonists are bronchodilators used for the management of persistent asthma symptoms, especially nocturnal asthma. They represent different classes of drug with differing side-effect profiles. OBJECTIVES: To assess the comparative efficacy, safety and side-effects of long-acting beta-agonists and theophylline in the maintenance treatment of asthma. SEARCH STRATEGY: Randomised, controlled trials (RCTs) were identified using the Cochrane Airways Group register. The register was searched using the following terms: asthma and theophylline and long acting beta-agonist or formoterol or foradile or eformoterol or salmeterol or bambuterol or bitolterol. Titles and abstracts were then screened to identify potentially relevant studies. The bibliography of each RCT was searched for additional RCTs. Authors of identified RCTs were contacted for other relevant published and unpublished studies. SELECTION CRITERIA: All included studies were RCTs involving adults and children with clinical evidence of asthma. These studies must have compared oral sustained release and/or dose adjusted theophylline with an inhaled long-acting beta-agonist. DATA COLLECTION AND ANALYSIS: Potentially relevant trials, identified by screening titles and/or abstracts, were obtained. Two reviewers independently assessed full text versions of these trials to decided whether the trial should be included in the review, and assessed its methodological quality. Where there was disagreement between reviewers, this was resolved by consensus, or reference to a third party. Data were extracted by two independent reviewers. Inter-rater reliability was assessed by simple agreement. Study authors were contacted to clarify randomisation methods, provide missing data, verify the data extracted and identify unpublished studies. Relevant pharmaceutical manufacturers were also contacted. MAIN RESULTS: Six trials met the inclusion criteria. Five used salmeterol and one, biltoterol. They were of varying quality. There was a trend for salmeterol to improve FEV1 more than theophylline in three studies and salmeterol use was associated with more symptom free nights. Bitolterol, used in only one study, was reported to be less effective than theophylline. Subjects taking salmeterol experienced fewer adverse events than those using theophylline (Relative Risk 0.38; 95%Confidence Intervals 0.25, 0.57). Significant reductions were reported for central nervous system adverse events (Relative Risk 0.51; 95%Confidence Intervals 0.30, 0.88) and gastrointestinal adverse events (Relative Risk 0.32; 95%Confidence Intervals 0.17, 0.59). REVIEWER'S CONCLUSIONS: Salmeterol may be more effective than theophylline in reducing asthma symptoms including night waking and improving lung function. More adverse events occurred in subjects using theophylline when compared to salmeterol.

Adrenergic beta-Agonists↗

The effect of a Structured Question Grid on the validity and perceived fairness of a medical long case assessment.

PROBLEM: A perception that the reliability of our oral assessments of clinical competence was vitiated by lack of consistency in questioning. DESIGN: Parallel group controlled trial of a Structured Question Grid for use in clinical assessments. The Structured Question Grid required assessors to see the patient personally in advance of the student and to write down for each case the points they wished to examine. The Structured Question Grid limited assessors to two questions on each point, one designated a pass question and one at a higher level. Three basic science and three clinical reasoning issues were required, so that a total of 12 questions was allowed. SETTING: Small (70 students/year) undergraduate medical school with an integrated, problem-based curriculum. SUBJECTS: Sixty-seven students in the fourth year of a 5-year course were assessed, each seeing one patient and being examined by a pair of assessors. Assessor pairs were allocated to use the Structured Question Grid or to assess according to their usual practice. RESULTS: After the assessment but before being informed of the result the students completed a questionnaire on their experience and gave their performance a score between 0 and 100. The questions asked were based on focus group discussions with a previous student cohort, and concerned principally the perceived fairness and subjective validity of the assessment. The assessors independently completed a similar questionnaire, gave the student's performance a score between 0 and 100, and assigned an overall pass/fail grade. CONCLUSIONS: No difference was detected between students' or assessors' views of the fairness of the assessment for assessors who had used the Structured Question Grid compared to those who had not. Students whose assessors used the Structured Question Grid considered the assessment less representative of their ability. No difference was detected in the chance of students being assessed as failing or on the likelihood of a discrepancy between students' and assessors' ratings of students as passing or failing.

Clinical Competence↗

An experimental investigation of the role of iconic gestures in lexical access using the tip-of-the-tongue phenomenon.

The tip-of-the-tongue (TOT) state was induced in participants to test Butterworth & Hadar's (1989) theory that iconic gestures have a functional role in lexical access. Participants were given rare word definitions from which they had to retrieve the appropriate lexical item, all of which had been rated high in imageability. Half were free to gesture and the other half were instructed to fold their arms. Butterworth & Hadar's theory (1989) would predict, first, that the TOT state should be associated with iconic gesture and, second, that such gestures should assist in this lexical retrieval function. In other words, those who were free to gesture should have less trouble in accessing the appropriate lexical items. The study found that gestures were associated with lexical search. Furthermore, these gestures were sometimes iconic and sufficiently complex and elaborate that naive judges could discriminate the lexical item the speaker was searching for from a set of five alternatives, at a level far above chance. But often the gestures associated with lexical search were not iconic in nature, and furthermore there was no evidence that the presence of the iconic gesture itself actually helped the speaker find the lexical item they were searching for. This experimental result has important implications for models of linguistic production, which posit an important processing role for iconic gestures in the processes of lexical selection.

Adult↗

GR196429: a nonindolic agonist at high-affinity melatonin receptors.

N-[2-[2,3,7,8-tetrahydro-1H-furo(2,3-g)indol-1-yl]ethyl]acetamide (GR196429) is a novel, nonindolic melatonin receptor agonist. GR196429 had high affinity for human mt1 (pKi 9.9) and MT2 (pKi 9.8) receptors expressed in Chinese hamster ovary cells and for 2-[125I]-iodomelatonin binding sites in human cerebellum, guinea pig superior colliculus and hypothalamus and chicken retina and tectum (pKi 8.8-9.5). GR196429 was inactive at a wide range of other hormone and neurotransmitter receptors. In Chinese hamster ovary cells expressing human mt1 or MT2 receptors, both melatonin and GR196429 dose-dependently inhibited forskolin-stimulated cAMP accumulation. In rabbit isolated retina, GR196429 inhibited calcium-dependent [3H]-dopamine release with potency (IC50 30 pM) and maximum effect (76 +/- 5% at 1 nM) similar to those of melatonin. The response was antagonized by the melatonin receptor antagonist luzindole (1 microM). In slices of rat brain suprachiasmatic nucleus, perfusion (1 h) with GR196429 at zeitgeber time 10 phase advanced the circadian peak in neuronal activity measured on the following day, with a maximum phase advance of 2.7 +/- 0.3 h at 10 pM and an EC50 of 0.6 pM, results that indicated a melatonin-like action on the phase of the circadian clock. CNS penetration and duration of receptor occupancy was determined in an ex vivo radioligand binding assay. In membranes of guinea pig superior colliculus prepared 30 min after administration of GR196429 (s.c.), 2-[125I]-iodomelatonin binding was inhibited with an ED50 of 0.04 mg/kg. After a dose of 1 mg/kg, binding was significantly inhibited for at least 3 h. Thus GR196429 is a potent and selective agonist at high-affinity melatonin receptors, which modulates circadian rhythms in an in vitro model of the circadian clock and which readily penetrates the CNS.

Animals↗

Angiotensin-converting enzyme inhibition, angiotensin, and cognition.

In these studies, we have investigated possible cognition-enhancing effects of angiotensin-converting enzyme (ACE) inhibition, and putative neurochemical correlates for these actions. In a mouse habituation model, ACE inhibitors improved basal performance and antagonized scopolamine-induced deficits. The performance of aged mice and those with lesions of the nucleus basalis was also improved. ACE inhibition also improved scopolamine-impaired performance of rats in a swim-maze model. Neurochemical studies showed that a low dose (10 micrograms/kg i.p.) of ceranapril caused significant alterations in ex vivo rat brain catecholamine levels in the nucleus accumbens, amygdala, and septum. In further studies, angiotensin II (Ang II) was shown to decrease potassium-stimulated [3H] acetylcholine release from slices of rat entorhinal and human temporal cortex, an effect that could be antagonized by the angiotensin receptor antagonist [1-sar,8-thr]Ang II. It is concluded that ACE inhibition can improve both basal and impaired performance in animal models of learning, and that this improvement may be in part a consequence of the removal by ACE inhibition of an inhibitory tone on central acetylcholine release, and/or an effect on central catecholaminergic function.

Acetylcholine↗

The selective CCK-B receptor antagonist L-365,260 enhances morphine analgesia and prevents morphine tolerance in the rat.

The effects of the selective CCK-A antagonist L-365,031 and the selective CCK-B antagonist L-365,260 on morphine analgesia and opiate tolerance and dependence in rats were examined. L-365,031 and L-365,260 had no effect on baseline pain thresholds in the radiant heat tail flick test but enhanced analgesia induced by a submaximal dose of morphine (4 mg/kg). Similarly, L-365,260 did not effect pain thresholds in the paw pressure test but enhanced morphine analgesia in this model. Rats injected twice daily for 6 days with incremental doses of morphine became tolerant to the analgesic effects of the drug. Twice daily injections of either 8 mg/kg L-365,031 or 0.2 mg/kg L-365,260 prevented the development of tolerance to morphine analgesia. In contrast, L-365,260 had no influence on the development of opiate dependence in these animals, as assessed by naloxone-precipitated withdrawal. The results of the present study, when considered together with previous data, indicate that the rank order of potency of non-peptide CCK antagonists for enhancing morphine analgesia is L-365,260 greater than MK-329 greater than L-365,031. This rank order correlates well with the potency of the antagonists in blocking CCK-B receptors in rodents and suggests that CCK/opiate interactions in this species are mediated by CCK-B receptors.

Analgesia↗

The effects of ondansetron, a 5-HT3 receptor antagonist, on cognition in rodents and primates.

The selective 5-HT3 receptor antagonist, onansetron, has been assessed in three tests of cognition in the mouse, rat and marmoset. In a habituation test in the mouse, ondansetron facilitated performance in young adult and aged animals, and inhibited an impairment in habituation induced by scopolamine, electrolesions or ibotenic acid lesions of the nucleus basalis magnocellularis. Arecoline failed to improve basal performance in young adult mice but inhibited the impairment caused by scopolamine and lesions of the nucleus basalis magnocellularis. In the T-maze reinforced alternation task in rats, ondansetron and arecoline antagonised a scopolamine-induced impairment. In an object discrimination and reversal learning task in the marmoset, assessed using a Wisconsin General Test Apparatus, ondansetron improved performance in a reversal learning task. We conclude that ondansetron potently improves basal performance in rodent and primate tests of cognition and inhibits the impairments in performance caused by cholinergic deficits.

Aging↗

Autosomal dominant familial spastic paraplegia: report of a large New England family.

A large New England family with autosomal dominant familial spastic paraplegia is described. In a pedigree of 173 individuals, 71 affected individuals are identified. Seventeen cases examined by the authors are described with regard to the natural history of FSP in this family. A staging system for following progress and planning interventions is proposed. Three illustrative cases are presented. In this family, FSP is found to have a homogeneous clinical course with nearly complete penetrance. Onset occurs at or before 3 years of age with involvement limited to the lower extremities. After the initial onset, no significant progression was noted. Early aggressive habilitative care may result in more functional ambulation.

Adolescent↗

The effects of ACE inhibitors captopril and SQ29,852 in rodent tests of cognition.

The ACE inhibitors captopril and SQ29,852 enhanced a habituation response to bright illumination in young adult and aged mice measured in a two-compartment light/dark test box. The treatments also antagonised a scopolamine-induced impairment and SQ29,852 was approximately 100 times more potent than captopril. In rats trained on a reinforced alternation paradigm in a T-maze, aged rats, as compared to young adults, showed a reduction in choice performance which was antagonised by SQ29,852. The impairment in choice performance in the T-maze induced by scopolamine in young adult rats was antagonised by SQ29,852 whilst captopril only delayed the onset of the scopolamine-induced impairment. SQ29,852 also antagonised scopolamine-impaired escape latency in a spatial learning/memory paradigm in a water-maze test. The effects of SQ29,852 in the rat were achieved within a somewhat restricted dose range. The ability of captopril and SQ29,852 to increase performance in the behavioural tests is discussed in terms of an antagonism of angiotensin converting enzyme to remove an inhibitory role of angiotensin II on central cholinergic function.

Age Factors↗

The 5-HT1A agonist 8-OH-DPAT increases consumption of palatable wet mash and liquid diets in the rat.

The 5-HT1A agonist 8-OH-DPAT, at a dose of 30 micrograms/kg, enhanced the consumption of sweetened wet mash and sweetened milk in non-deprived rats. In partially satiated rats, sensitivity to the hyperphagic effect of 8-OH-DPAT on wet mash intake was substantially increased, so that the minimally effective dose was reduced to 3 micrograms/kg. Similarly, 8-OH-DPAT was more efficacious in increasing milk intake in satiated rats. Thus, 30 and 40 micrograms/kg 8-OH-DPAT produced a 4-fold increase of milk intake in completely satiated rats compared to a 2-fold increase in partially satiated animals at a dose of 30 micrograms/kg. The increased intake of liquid and wet mash diets observed after treatment with low doses of 8-OH-DPAT argues against the involvement of non-specific gnawing in the increased consumption of solid food produced by the drug. Rather, the data suggest that 8-OH-DPAT may specifically stimulate appetite by counteracting a tonic serotonergic inhibition of feeding. The present experiments also showed that 8-OH-DPAT attenuates fenfluramine-induced anorexia which is thought to depend on increased serotonergic neurotransmission.

8-Hydroxy-2-(di-n-propylamino)tetralin↗