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R J Marshall

Publications and source records attributed to R J Marshall.

At least 37 records · Page 2Linked to original sources
PubMed1997

Anesthetic activity of novel water-soluble 2 beta-morpholinyl steroids and their modulatory effects at GABAA receptors.

(3 alpha,5 alpha)-3-Hydroxypregnan-20-ones and (3 alpha,5 alpha)-3-hydroxypregnane-11,20-diones bearing a 2 beta-morpholinyl substituent were synthesized, and the utility of these steroids as anesthetic agents was evaluated through determination of their potency and duration of hypnotic activity in mice after intravenous administration. Alkylation of the morpholinyl substituent or chlorination at C-21 afforded the novel amino steroids (2 beta,3 alpha,5 alpha)-3-hydroxy-2-(2,2-dimethyl-4-morpholinyl)-pregnane-11,20-dione (19) and (2 beta,3 alpha,5 alpha)-21-chloro-3-hydroxy-2-(4-morpholinyl)pregnan-20-one (37) that were more potent and advantageously produced shorter sleep times than related compounds which were previously reported. Furthermore, salts of these and other amino steroids generally retained good aqueous solubility. In a radioligand binding assay the compounds inhibited the specific binding of [35S]-tert-butyl bicyclophosphorothionate to rat whole brain membranes, and in an electrophysiological assay they potentiated GABAA receptor-mediated currents recorded from voltage-clamped bovine chromaffin cells. These in vitro results are consistent with the anesthetic activity of the amino steroids being related to their modulatory effects at GABAA receptors.

Anesthesia↗
PubMed1997

Salt tolerance of EMRSA-16 and its effect on the sensitivity of screening cultures.

The salt (NaCl) tolerance of methicillin-resistant Staphylococcus aureus (EMRSA)-16 was compared with 18 other MRSA isolates by an agar incorporation technique. The NaCl minimum inhibitory concentration (MIC) of EMRSA-16 was 7% which compared with an MIC50 of 7%, MIC90 of 10%, range (5.5-10.5%) for the other isolates. Study of the growth kinetics in broth containing NaCl at concentrations up to 10% indicated complete inhibition of growth by 7 and 10% NaCl and partial inhibition by 5%. Addition of EMRSA-16 at inocula of < or = 1 cfu/mL into salt broths revealed lower than expected EMRSA recovery from broths containing 5, 7.5 and 10% NaCl. Two and a half per cent NaCl broths were not inhibitory. Selective broth containing 2.5% NaCl should be considered for use when screening for EMRSA-16.

Culture Media↗
PubMed1997

Assessment of exposure misclassification bias in case-control studies using validation data.

It has recently been shown that the bias due to misclassification of a binary exposure in case-control studies can be simply expressed in terms of so-called quality indices. Quality indices are measures of the degree of misclassification that are symmetric with respect to the true and measured exposure. They can be estimated from sub-study validation data and used to estimate the bias. Bias is not present if quality indices are nondifferential with respect to cases and controls. In this article the sampling distribution of these indices is investigated by developing formulae for their standard errors and these formulae are used to derive the standard error of the estimated bias. Simulation studies are used to confirm the validity of the formulae. The formulae are used to assess the bias in two studies of risk factors for Sudden Infant Death Syndrome (SIDS) and can be applied to the assessment of diagnostic tests.

Anti-Bacterial Agents↗
PubMed1996

The anaesthetic action and modulation of GABAA receptor activity by the novel water-soluble aminosteroid Org 20599.

The anaesthetic profile of a novel water-soluble aminosteroid, Org 20599 [(2 beta, 3 alpha, 5 alpha)-21-chloro-3-hydroxy-2-(4-morpholinyl)pregnan-20-one methanesulphonate], and the ability of the compound to allosterically regulate the activity of the GABAA receptor, have been studied in comparison to the properties of established intravenous general-anaesthetic agents. Intravenously administered Org 20599 produced a rapid onset, short duration loss of the righting reflex in mice. The anaesthetic potency of Org 20599 was comparable to that of the steroids 5 alpha-pregnan-3 alpha-ol-20-one or alphaxalone, and exceeded that of propofol, thiopentone or pentobarbitone. Org 20599 and the reference anaesthetic agents allosterically displaced the binding of [35S]-t-butylbicyclophosphorothionate (TBPS) from GABAA receptors of rat-brain membranes with the order of potency: 5 alpha-pregnan-3 alpha-ol-20-one > Org 20599 > alphaxalone > propofol > thiopentone > pentobarbitone. At human recombinant alpha 1, beta 2, gamma 2L subunit-containing GABAA receptors expressed in Xenopus laevis oocytes, the anaesthetic agents produced a concentration-dependent and reversible potentiation of the peak amplitude of GABA-evoked currents. A similar positive allosteric action of Org 20599 was observed for the GABAA receptors expressed by bovine adrenal chromaffin cells maintained in culture. The rank order of potency in the aforementioned assays was identical to that determined from the displacement of TBPS binding. At concentrations greater than those required for potentiation of GABA, the anaesthetics exhibited GABA-mimetic effects with a rank order of potency that paralleled their modulatory activity. Such direct agonism varied greatly in maximal effect between compounds. The modulatory and direct agonist actions of Org 20599 were additionally confirmed utilizing rat hippocampal neurones in culture. The results indicate Org 20599 to be a potent and short-acting intravenous anaesthetic agent in mice and suggest positive allosteric regulation of GABAA receptor function to be a plausible molecular mechanism of action for the drug.

Anesthetics↗
PubMed1995

A program to implement a search method for identification of clinical subgroups.

A procedure for identifying subgroups that are homogeneous with respect to an outcome variable is described. The method, search partition analysis (SPAN), is formulated in terms of a numeric outcome variable y and a set of predictors, explanatory variables or risk factors x = x1,x2,...,x p. The objective is to split observations into two groups by a binary partition, specified using Boolean expressions of the predictors, x, such that y is as homogeneous as possible in the resultant groups; uniformly ¿low' in one and uniformly ¿high' in the other. Subgroups within each of the two groups can be identified from the Boolean expressions. SPAN implements a search for the ¿best' partition from among a class of regular Boolean expressions. Features of the method are described, including how to measure partition homogeneity, complexity penalizing, search strategies and subgroup definition and representation. The approach is illustrated with analyses of predictors of low birth weight and predictors of impaired glucose tolerance for screening purposes.

Bias↗
PubMed1995

Research and development of aminosteroid neuromuscular blocking agents: past and future.

This article attempts to summarize more than 25 years of chemistry and pharmacology research aimed at the search for clinically useful muscle relaxants based on an amino-androstane skeleton. This research strategy has produced three clinically useful drugs (pancuronium, vecuronium and rocuronium), and in addition has demonstrated that it is indeed possible to design a non-depolarizing neuromuscular blocker with the onset/offset characteristics of suxamethonium. Lastly, much has been learned about the variable clinical predictiveness of data obtained in various animal species with these compounds. This factor is probably mainly responsible for the difficulties and delay in producing the non-depolarizing suxamethonium equivalent.

Animals↗
PubMed1994

Misclassification of exposure in case-control studies: assessment by quality indices.

Misclassification of a binary exposure in case-control studies is usually assessed by sensitivity and specificity of the measured exposure. Sensitivity and specificity do not adequately measure the degree of misclassification because they assess only the proportion of truly exposed (or unexposed) subjects who are misclassified by the defective measurement. They do not account for the proportion of subjects, categorized by the defective measurement as either exposed or unexposed, who are misclassified, in other words, the predictive value of the measurement. A more appropriate way of measuring misclassification is by "quality indices" that take both of these criteria into account and that are essentially rescaled sensitivity and specificity, or predictive value, measures. I present the relation between measured and actual odds ratios in terms of quality indices. If quality indices are nondifferential or proportional, there is no misclassification bias to the odds ratio. The relation offers a new approach to correcting measured odds ratios.

Bias↗
PubMed1994

Confounder prevalence and stratum-specific relative risks: implications for misclassified and missing confounders.

In this article, I describe a simple relation between stratum-specific risk ratios and the distribution of strata in disease-exposure categories. The relation does not seem well known, but it presents an alternative way to view how to make adjustments to biased stratum-specific relative risk estimates when bias is due to either a misclassified or missing confounding variable. For instance, it demonstrates that there would be no misclassification bias if categories of a confounder surrogate have the same prevalence as those of the true confounder, in each disease-exposure category, regardless of whether the surrogate is a good or bad approximation to the true confounder. It also provides an insight into the conditions required to ensure uniformity of stratum-specific relative risks.

Confounding Factors, Epidemiologic↗
PubMed1994

An overview of the pharmacology of rocuronium bromide in experimental animals.

In various animal species anaesthetized with a-chloralose (cats and pigs) or pentobarbitone (Beagle dogs and Rhesus monkeys), rocuronium has been shown to be a readily reversible, non-depolarizing neuromuscular blocking agent with a similar duration of action as vecuronium but a 6-10 fold lower potency. The outstanding features of its action is rapidity of onset. It is not expected to have any marked cardiovascular or autonomic side-effects when used in the neuromuscular blocking dose range. There is no evidence of any selective pre-junctional effect and there is no clinically relevant inhibition of acetycholinesterase. Screening in rats has not demonstrated any oestrogenic, androgenic, anabolic, glucocorticoid-like or gonad-inhibiting properties, although there was a slight increase in pituitary weight in male rats.

Acetylcholinesterase↗
PubMed1993

Analysis of case-crossover designs.

The case-crossover design provides a means to study the effects of transient exposures on the risk of acute illness, for example, the effects of drinking alcohol on the immediate risk of a heart attack. Only cases are required by the design, since each case is effectively its own control; what a case was doing at the time of an acute event is compared with what the case would have been doing usually. Maclure has described an approach based on the Mantel-Haenszel method of analysis. It is shown here how the analysis of case-crossover designs can be achieved by a method of maximum likelihood. The method is quite general and, in principle, can be used to analyse the joint effects of many transient exposures. For binary exposures the Mantel-Haenszel approach is an approximate solution to the likelihood equations. In practice, case-crossover designs are limited by the information available on each case's 'usual' behaviour. Extracting such information requires in-depth questioning, but, in principle, it can be obtained. To do so requires careful questionnaire design. The approach is illustrated by analysis of 24 hour alcohol consumption and the risk of myocardial infarction. The problem with this analysis is how to estimate the probability of what a case would 'usually' have been doing from information on drinking frequency.

Adult↗
PubMed1993

Physicochemical properties accounting for cheese texture.

Perception of texture is a complex dynamic series of events which cannot be modelled easily by physicochemical measurements. Results using cheese analogues suggest that moisture and fat are key components in determining texture because they soften the protein matrix and provide weaknesses through which the cheeses fracture. These characteristics are sensed as firmness and work during chewing. Possible models are proposed for further investigation of the tactile determinants of cognitive mechanics involved in cheese texture description.

Cheese↗
PubMed1993

A Master of Science course at the Cardiff School of Medical Photography.

Formal teaching and training in medical photography at Cardiff started in 1969 when a School of Medical Photography was established, as part of the Department of Medical Illustration, at the Cardiff Royal Infirmary. In the early 1970s the school was transferred with the Medical Illustration Department to the newly built University Hospital of Wales, and housed in planned accommodation at what is now the Institute of Health Care Studies. The school offered courses in medical photography at the level of the qualifying examinations of the Professional Institutes, to suitably qualified in-service students appointed to the Medical Illustration Department as Trainee Medical Photographers. In 1990, the University of Wales approved a Master of Science course in Medical Illustration (Photography and Video) offered by the school. The course is available both to in-service students of the school and to practising medical photographers as mature students on a distance learning programme. Details of the new course and its delivery are given.

Education, Graduate↗
PubMed1992

Pneumonia due to Legionella bozemanii and Chlamydia psittaci/TWAR following renal transplantation.

Chlamydia and Legionella are recognized causes of atypical pneumonia. A case of pneumonia due to Chlamydia psittaci/TWAR and Legionella bozemanii following renal transplantation is described. Legionella bozemanii infection was diagnosed by a rise in antibodies and by isolation of the organism from bronchoscopy specimens. It is unusual to find pneumonia caused concomitantly by two such agents. This case, despite the fatal outcome, emphasises the necessity for a comprehensive approach to the diagnosis of atypical pneumonia, including culture for Legionella, especially in immunocompromised patients.

Female↗