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Biomedical subjects

J Marchant

Publications and source records attributed to J Marchant.

At least 19 recordsLinked to original sources

Generation game.

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Animals↗

A beneficial aspect of a CB1 cannabinoid receptor antagonist: SR141716A is a potent inhibitor of macrophage infection by the intracellular pathogen Brucella suis.

The psychoactive component of marijuana, delta9-tetrahydrocannabinol (THC) suppresses different functions of immunocytes, including the antimicrobicidal activity of macrophages. The triggering of cannabinoid receptors of CB1 and CB2 subtypes present on leukocytes may account for these effects. We investigated the influence of specific CB1 or CB2 receptor antagonists (SR141716A and SR144528, respectively) and nonselective CB1/CB2 cannabinoid receptor agonists (CP55,940 or WIN 55212-2) on macrophage infection by Brucella suis, an intracellular gram-negative bacteria. None of the compounds tested affected bacterial phagocytosis. By contrast, the intracellular multiplication of Brucella was dose-dependently inhibited in cells treated with 10-500 nM SR141716A and 1 microM SR141716A-induced cells exerted a potent microbicidal effect against the bacteria. SR144528, CP55,940, or WIN 55212-2 did not affect (or slightly potentiated) the growth of phagocytized bacteria. However, CP55,940 or WIN 55212-2 reversed the SR141716A-mediated effect, which strongly suggested an involvement of macrophage CB1 receptors in the phenomenon. SR141716A was able to pre-activate macrophages and to trigger an activation signal that inhibited Brucella development. The participation of endogenous cannabinoid ligand(s) in Brucella infection was discussed. Finally, our data show that SR141716A up-regulates the antimicrobial properties of macrophages in vitro and might be a pharmaceutical compound useful for counteracting the development of intramacrophagic gram-negative bacteria.

Animals↗

Initiation of IP(3)-mediated Ca(2+) waves in Xenopus oocytes.

Inositol (1,4,5)-trisphosphate (IP(3)) evokes Ca(2+) liberation in Xenopus oocytes as elementary events (Ca(2+) puffs) that become coupled to propagate Ca(2+) waves with increasing [IP(3)]. To investigate this transition between local and global Ca(2+) signaling, we developed an optical method for evoking rapid subcellular Ca(2+) elevations, while independently photoreleasing IP(3) and simultaneously recording confocal Ca(2+) images. Focal Ca(2+) elevations triggered waves within 100 ms of photoreleasing IP(3), compared with latencies of seconds following photorelease of IP(3) alone. Wave velocity varied with [IP(3)] but was independent of time after photorelease of IP(3), indicating that delayed wave initiation did not involve slow binding of IP(3) to its receptors. The amount of Ca(2+) required to trigger a wave was approximately 10-fold greater than the average size of puffs, and puffs showed no progressive increase in magnitude before waves initiated. Instead, Ca(2+) puffs contributed to a slow rise in basal free [Ca(2+)], which further increased puff frequency and sensitized IP(3) receptors so that individual events then triggered waves. Because the wave threshold is much greater than the size of the elementary puff, cells can employ both local and global signaling mechanisms, and the summation of stochastic behavior of elementary events allows generation of reproducible periodic waves.

Animals↗

Prevention of cross infection during outpatient spirometry.

Lung function apparatus may be a source of cross infection in patients with cystic fibrosis and may be prevented using a 'bag in bottle' system. As this system has never been validated in children the flow volume loops performed using a Vitalograph Compact in the usual way were compared with results obtained blowing into the bag and bottle system, in random order, in 20 children with asthma (age 8-15 years). Three reproducible flow volume loops were recorded for each apparatus. There was no order effect. Mean (SE) results for forced expiratory volume in one second, forced vital capacity (FVC), peak expiratory flow rate, and maximum expiratory flow at between 75% and 25% of FVC showed respectively that the bag in bottle results were significantly greater than those obtained blowing directly into the spirometer by 90 (17) ml, 12.7 (5.1) l/min, 130 (60) ml/min. Although statistically significant, these differences are within the previously described coefficients of variation for children with cystic fibrosis and are of doubtful clinical relevance. It is concluded that the bag in bottle system does not introduce any important systematic error. It potentially offers absolute protection from cross infection.

Adolescent↗

Assessment of hyperinflation in children with cystic fibrosis.

BACKGROUND: Radiological estimates of hyperinflation are used in several clinical and radiographic scoring systems for cystic fibrosis, but it is not known if these estimates of hyperinflation are related to measured total lung capacity. METHODS: Comparison was made of independent clinical estimates of hyperinflation from chest radiographs with objective plethysmographic and radiographic measurements of total lung capacity in 25 children with cystic fibrosis. RESULTS: There was good agreement between plethysmographic and radiographic measurements. Clinical estimation correctly predicted the extremes of hyperinflation, but grading was no more than 50% accurate in all other groups. CONCLUSION: The degree of hyperinflation cannot be estimated by inspecting chest radiographs in many children with cystic fibrosis. This does not invalidate the scoring systems, but suggests that a better term than "hyperinflation" should be sought.

Adolescent↗

Attitudes towards prenatal diagnosis and carrier screening for cystic fibrosis among the parents of patients in a paediatric cystic fibrosis clinic.

The parents of all children attending the Royal Brompton National Heart and Lung Hospital cystic fibrosis paediatric clinic were asked to complete an anonymous postal questionnaire addressing attitudes towards prenatal diagnosis and population carrier screening for cystic fibrosis (CF); 65% (170/261) of parents responded. Of the respondents, 92% would support the introduction of a population screening test to detect carriers of CF and 19% felt such a test should be mandatory. A total of 64% of CF parents felt they would choose not to have any further children in the knowledge that they were both carriers, 74% would choose to have a prenatal test if they became pregnant, 44% would consider terminating an affected pregnancy, 33% would not, and 23% were unsure. Overall, 72% of respondents indicated they would choose to avoid having a further child with CF either by not having further children or by terminating an affected pregnancy.

Attitude to Health↗

A comparison of two ranitidine intravenous infusion regimens in critically ill patients.

The effect of two ranitidine intravenous infusion regimens on intragastric pH was studied in 134 critically ill patients admitted to 15 intensive care units. Intragastric pH was determined hourly for 30 hours. Those patients whose intragastric acidity fell below pH 4.0 for 3 or more of the first 6 hours were considered 'at risk' of developing stress-related gastric lesions and randomized to receive a 50 mg bolus of ranitidine together with a continuous intravenous infusion of either 0.125 or 0.25 mg kg-1 h-1 ranitidine for 24 hours. The maximal elevation in intragastric pH was achieved within 12 hours. The median intragastric pH for the last 20 hours of the infusion period was 5.9 for the higher dose group and 5.6 for the lower dose group. The increase in intragastric pH achieved by the two dosage regimens did not differ significantly throughout the 24 hour period. Patients having two or more of five major risk factors (head injury, major trauma, sepsis, respiratory failure/insufficiency and major surgery) had better overall control of intragastric pH on the higher dose of ranitidine than those receiving the lower dose. The majority of intensive care patients are likely to receive satisfactory treatment with the lower dosage regimen that was tested (0.125 mg kg-1 h-1). Those with multiple risk factors may, however, require treatment with higher doses of ranitidine (0.25 mg kg-1 h-1).

Adolescent↗

Reducing multiple problem behaviours in a profoundly retarded child.

The purpose of the present paper is to describe two behaviour management programmes developed for a profoundly retarded child in a special education classroom. The target behaviours were:(1)inappropriate object contract,(2)wild running about the room, and(3)consistent refusal to eat. Literature was reviewed in an effort to fine information which would help in the management of these behaviours. However,only a limited number of studies were found to be directly relevant. Salzberg & Napolitan(1974)modified inappropriate object contact through physical restraint. Neumann & Gaoni(1975)increased food consumption in a woman suffering from anorexia nervosa by using preferred foods. No literature was found which demonstrated the suppression of wild running behavior.

Behavior Therapy↗