PubMed Health⌕ Search

Biomedical subjects

P W Marshall

Publications and source records attributed to P W Marshall.

10 recordsLinked to original sources
PubMed1997

A comparison of the effects of aspirin on bleeding time measured using the Simplate method and closure time measured using the PFA-100, in healthy volunteers.

AIMS: The aim of this study was to compare the effects of aspirin on platelet function as measured by the 'classical' template bleeding time with a new ex vivo method measuring closure times using the PFA-100 machine. Platelet aggregation in response to arachidonic acid was also measured ex vivo. METHODS: The trial was a randomized, double-blind, placebo-controlled crossover design, with each volunteer taking 750 mg aspirin (BP) or placebo, three times a day for 5 days, with an 18 day wash-out period between treatments. Bleeding times and closure times were measured before the first dose on the first day and 0.5 h after the last dose on the fifth day of each treatment period. They were also measured 2 weeks after the last day of the trial. RESULTS: Baseline bleeding times (pre-placebo) were 415 s using the Simplate, whilst baseline closure times were 115 s using the PFA-100. Aspirin treatment caused an increase of both the template bleeding time (61%) and the closure time of the PFA-100 (79%) when compared with the effects of placebo. The platelet aggregatory response to arachidonic acid was completely inhibited following aspirin treatment and was unaffected following placebo. Two weeks after the end of the trial, all values had returned to pre-treatment levels. The template bleeding time was unaltered in 1 of the 12 volunteers during aspirin treatment and was significantly prolonged in 3 of the 12 volunteers during placebo treatment. The PFA-100 closure time was unaltered in 1 of the 12 volunteers during aspirin treatment and was prolonged in 1 subject during placebo treatment. CONCLUSIONS: The change in closure time using the PFA-100 is as sensitive and reproducible to the effects of aspirin on platelet function as is the template bleeding time test. However, the PFA-100 produced less variable effects with fewer false positive results.

Adult↗
PubMed1993

ICI D7288, a novel sinoatrial node modulator.

We evaluated the cardiovascular effects of the sinoatrial (SA) node modulating agent, ICI D7288, in guinea pig isolated atria and SA node, anaesthetised and exercising dogs, and conscious rats. ICI D7288 (0.1-100 microM) caused a reduction in spontaneous beating rate in guinea pig isolated right atria without affecting the contractile force of paced left atria. The effect was associated with a reduction in the rate of diastolic depolarisation recorded intracellularly from pacemaker cells in the SA node. In anaesthetised dogs, ICI D7288 (0.02-1 mg/kg intravenously, i.v.) caused a dose-related reduction in heart rate (HR) without directly affecting left ventricular (LV) contractility. Exercise tachycardia in dogs was reduced by the compound (0.1-1 mg/kg i.v. and 0.3-10 mg/kg orally, p.o.). The increase in cardiac output (CO) during exercise was well maintained unless the tachycardia was reduced by > 30%, when it was attenuated. Administration of ICI D7288 p.o. (3-100 mg/kg) to conscious rats reduced HR by < or = 40%, but had no effects on blood pressure (BP). We suggest that ICI D7288, through its selective effects on the SA node, may be of use in treatment of ischaemic heart disease to reduce increased HR without impairing cardiac function.

Action Potentials↗
PubMed1992

Attenuation of chemically induced defence response by 5-HT1 receptor agonists administered into the periaqueductal gray.

The ability of 5-HT1 receptor agonists to modulate a chemically induced defence response has been studied in Lister hooded rats. Microinjections of the excitatory amino acid D,L-homocysteic acid (DLH) in both rostral and caudal dorsal periaqueductal gray matter (PAG) caused explosive motor behaviour characteristic of defence. This behaviour was quantified in terms of response duration, arena revolutions and number of defensive jumps. Direct administration into the PAG of either 5-carboxamidotryptamine (5-CT) or 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT) produced behaviours (decreased exploratory rearing, dose related onset of flat body posture) indicative of 5-HT1A receptor activation. Pretreatment with either 5-CT or 8-OHDPAT directly in the PAG caused a significant attenuation, and in some cases a complete abolition, of the DLH evoked response. These agonists share high affinity in vitro for the 5-HT1A receptor. Thus the results suggest that in vivo activation of 5-HT1A receptors mediates an antiaversive response with respect to defensive behaviour elicited by specific chemical stimulation of the dorsal PAG.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1984

In-vitro activity of enoxacin against aminoglycoside-resistant gram-negative bacilli and other clinical isolates.

The in-vitro activity of enoxacin was tested against 500 clinical isolates of Gram-negative bacilli that were resistant to one or more of gentamicin, tobramycin and amikacin, and against 1060 recent consecutive clinical isolates of Gram-negative bacilli and Gram-positive cocci. Enoxacin was active against staphylococci (MICs less than or equal to 4 mg/l) but less active against Streptococcus faecalis (MICs mostly 8 mg/l). It was active against Pseudomonas aeruginosa (MICs 0.5-4 mg/l) and very active against Enterobacteriaceae. In the series of consecutive isolates 97% of Enterobacteriaceae had MICs less than or equal to 1 mg/l. The aminoglycoside-resistant series of Enterobacteriaceae included more strains with higher MICs (13% were 2-4 mg/l and 10% were greater than or equal to 8 mg/l); the majority of the isolates with MICs greater than or equal to 8 mg/l); the majority of the isolates with MICs greater than or equal to 8 mg/l were Serratia marcescens and Providencia spp. Among the non-fermenting species the least sensitive were Acinetobacter calcoaceticus and Ps. maltophilia. Enoxacin-resistant strains of Enterobacteriaceae were resistant to nalidixic acid, but nalidixic acid-resistant strains ranged from fully sensitive to highly resistant to enoxacin.

Aminoglycosides↗
PubMed1980

A model of reflex tracheal constriction in the dog.

1 A tracheal pouch with its nerve and blood supply intact has been prepared in situ in dogs. 2 Mechanical stimulation of the upper airways in dogs anaesthetized with chloralose induced a consistent increase in pouch pressure which was abolished by bilateral vagal section. 3 The response of the pouch following mechanical stimulation of the airways was abolished by intravenous pentobarbitone, atropine, administered systemically or when present in the pouch, and tetracaine, applied to the stimulus area or when present in the pouch. 4 Salbutamol had no inhibitory effects on the response regardless of its route of administration. 5 These results suggest that the increase in pouch pressure following mechanical stimulation of the upper airways is mediated by a vagal reflex arc. 6 The technique may distinguish between drugs the site of action of which is at the afferent or efferent end of this reflex arc.

Airway Resistance↗
PubMed1980

A model of irritant-induced bronchoconstriction in the spontaneously breathing guinea-pig.

1 Inhalation of an aqueous aerosol of citric acid caused bronchoconstriction in anaesthetized guinea-pigs which was abolished by bilateral vagal section. 2 Conscious guinea-pigs developed slow, laboured breathing within 90 s of exposure to citric acid aerosol. The onset of this pattern of breathing was delayed by prior aerosol administration of atropine, ipratropium bromide, isoprenaline and tetracaine. 3 The data suggest that exposure of guinea-pigs to citric acid may be a useful model of reflex bronchoconstriction.

Animals↗
PubMed1976

The mechansim of tachyphylaxis to ICI 74,917 and disodium cromoglycate.

Pre-incubation in vitro of sensitised peritoneal mast cells for 10 min with either ICI 74,917 (10-5 M) abolished the ability of either drug to inhibit histamine release when subsequently presented to the cells at the same time as antigen. In the case of disodium cromoglycate, tachyphylaxis was abolished by washing the cells after pre-incubation with the drug. The failure to abolish tachyphylaxis to ICI 74,917 was due to the high pre-incubation concentration employed, as at lower concentrations (10-8 M) tachyphylaxis to ICI 74917 was readily abolished by washing. Tachyphylaxis to these anti-allergic agents may be related to a physical blocking of drug receptor sites on or in mast cells.

Animals↗
PubMed1975

Inhibition of immediate hypersensitivity reactions in the rat by ICI 74,917 and disodium cromoglycate.

ICI 74,917, a potent inhibitor of IgE-mediated passive cutaneous anaphylaxis (PCA) in the rat, exhibited tachyphylaxis in that pre-dosing sensitised rats with a high dose of compound reduced the inhibitory effect on rat PCA of a second dose given at challenge. This phenomenon was most apparent when the pre-dose-challenge dose interval was 15--60 min. Similar findings were obtained using antigen-induced histamine release in vitro from rat peritoneal cells. In these respects, ICI 74,917 was similar to disodium cromoglycate (DSCG) although DSCG appeared less effective in inducing tachyphylaxis than ICI 74,917. There was no evidence in vivo or in vitro that a high dose of either DSCG or ICI 74,917 enhanced the activity of a second low dose of either drug given at challenge.

Animals↗