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Biomedical subjects

P Gilbert

Publications and source records attributed to P Gilbert.

At least 73 records · Page 4Linked to original sources
PubMed1999

Concomitant Block of the Rapid (I(Kr)) and Slow (I(Ks)) Components of the Delayed Rectifier Potassium Current is Associated With Additional Drug Effects on Lengthening of Cardiac Repolarization.

BACKGROUND: The delayed rectifier potassium current, which comprises both a rapid (I(Kr)) and as slow (I(Ks)) component, is a major outward current involved in repolarization of cardiac myocytes. I(Kr) is the target of most drugs that prolong repolarization, whereas electrophysiological effects resulting from combined block of I(Kr) and I(Ks) still need to be characterized. METHODS AND RESULTS: Studies in isolated, buffer-perfused guinea pig hearts were undertaken to compare lengthening of cardiac repolarization under conditions of I(Kr) block alone, I(Ks) Block alone, or combined block of I(Kr) and I(Ks). In protocol A, isolated perfusion with N-acetylprocainamide (NAPA) (I(Kr) block), indapamide (I(Ks) block), or combined NAPA/indapamide was performed at a pacing cycle length of 250 msec. Increases in monophasic action potential duration measured at 90% polarization (MAPD(90)) from baseline after perfusion with NAPA 100 µmol/L (IC(50) for block of I(Kr)) was 19 +/- 6 msed (P <.05), after indapamide 100 µmol/L (EC(50) for block of I(Ks)) 13 +/- 2 msec (P <.05), but 42 +/- 5 msec after combined NAPA 100 µmol/L and indapamide 100 µmol/L (P <.05 vs. baseline and isolated administrations), suggesting the possibility of excessive lengthening of cardiac repolarization by blocking both I(Kr) and I(Ks). As well, in protocol B where sequential perfusions with dofetilide (I(Kr) blocker), dofetilide/indapamide, and indapamide in the same hearts were used, combined dofetilide/indapamide infusion showed a greater increase in MAPD(90) during all pacing cycles studied (250 to 150 msec). CONCLUSIONS: Combined I(Kr) and I(Ks) block may lead to excessive lengthening of cardiac repolarization. This may predispose patients to proarrhythmia during coadministration of drugs.

Journal Article↗
PubMed1999

Recall of shame and favouritism in relation to psychopathology.

OBJECTIVES: There is good evidence that early rearing experiences affect vulnerability to subsequent psychopathology. Recent research on memories of rearing style have been influenced by attachment theory and have focused primarily on domains of emotional warmth and control. However, early experiences of being shamed, criticized and made to feel inferior, together with believing one's sibling is favoured over oneself, are also likely to play a role in vulnerability. This study therefore explored recall of being shamed and sibling favouritism. METHOD: A large community sample (N = 638) and a varied non-psychotic patient sample (N = 213) completed two recall of parent rearing scales (the PBI and EMBU). These gave measures of recall of emotional warmth, overprotection/control, being shamed and shown up, and self or sibling favouring. Participants also completed the SCL-90-R scale. RESULTS: Patients recalled less warmth, more control, more shame and more favouring of siblings than the community sample. The difference was greatest for shame, and following MANOVA analysis shame remained significantly different between the two groups even after controlling for emotional warmth and control. Similarly, recalling being less favoured than a sibling and shamed had robust associations with indicators of psychopathology and these were only marginally reduced when emotional warmth was controlled for. Moreover, hostility (as measured by the SCL-90-R) was specifically related to recall of being shamed but not emotional warmth. CONCLUSION: This study suggests that over and above issues of emotional warmth and control, recall of direct experiences of being shamed, feeling inferior and less favoured in a family, may be particularly pathogenic. They operate independently of warmth and may be especially important in proneness to hostile feelings. Given this, therapists may wish to specifically explore shame issues with patients.

Adolescent↗
PubMed1998

Extracellular products as mediators of the formation and detachment of Pseudomonas fluorescens biofilms.

Pseudomonas fluorescens B52 produces substantial biofilms at the air/liquid/solid interface of glass coverslips clamped vertically and partly submerged in liquid medium at 21 degrees C. Biofilm formation was maximal ca. 20-50 h after inoculation of the liquid medium and as indicated by environmental scanning electron microscopy (ESEM), contained large numbers of bacterial cells that were embedded within an extensive exopolymeric matrix. Incubation beyond 50 h led to reductions in biofilm which ESEM related primarily to losses of exopolymer. Both biofilm formation and the subsequent decline in exopolymer deposition was more rapid, and occurred to greater extents, when supernatants from two-day old cultures of B52 were used as the initial growth media. The addition of N-acyl-hexanoyl homoserine lactone to fresh growth medium had a similar effect upon biofilm formation as using spent culture medium. Homoserine lactones could not be demonstrated in spent culture supernatants by an Agrobacterium tumefaciens bioassay. An exopolysaccharide lyase was detected in spend culture media taken from dense biofilm cultures whose action was specifically directed towards biofilm exopolysaccharide. Results suggest that (i) cell-cell signals such as homoserine lactones are associated with the formation of P. fluorescens biofilms, (ii) the enzymic degradation of exopolymers has a specific role in the detachment of cells under starvation conditions, and (iii) whilst short chain (C6) exogenous homoserines can trigger such response in P. fluorescens, its own signal substance is likely to possess a longer (> C8) fatty acyl chain.

4-Butyrolactone↗
PubMed1998

Determination of 226Ra in mineral drinking waters by alpha liquid scintillation with rejection of beta-gamma emitters.

The radiotoxicity of radium isotopes (especially the long-half-life 226Ra) requires their monitoring in drinking waters or nuclear wastes. We studied the applicability of the PERALS method of detection (photon electron rejecting alpha liquid scintillation) for radium measurement. This method combines alpha liquid scintillation with pulse shape analysis for beta rejection and specific chemical extractants included in the scintillating cocktail. Radium is separated by an extractive-scintillator cocktail called RADAEX containing 2-methyl-2-heptylnonanoic acid (HMHN) and dicyclohexano-21-crown-7 (Cy(2)21C7) as extractant molecules. The variation of the radium extraction has been studied relative to pH, salt concentrations, anion and cation effects, and the volume ratio between aqueous and organic phases. The main parameter affecting the radium extraction in mineral drinking water is its complexation by inorganic anions, especially sulfate. Due to the lack of thermodynamic data, some complexation constants had to be determined. For instance, the value reported in this paper for radium sulfate (log beta = 2.58 +/- 0.22) is in good agreement with that from the literature. The knowledge of complexation constants allows the determination of radium extraction recovery for any solution when the inorganic anion concentrations had been measured by capillary zone electrophoresis. The detection limit for this technique is found to be equal to 0.006 Bq.L-1 using only 6 mL of sample solution for analysis. Several French mineral waters have been studied and the results compared with determinations of uranium and thorium concentrations by ICPMS and time-resolved laser induced fluorescence (TRLIF).

Beta Particles↗
PubMed1998

Realizing specialist and advanced nursing practice: a typology of innovative nursing roles.

This paper outlines the findings of the first phase of a Department of Health funded project: Realizing Specialist and Advanced Nursing Practice establishing the parameters of and identifying competencies for 'Nurse Practitioner' roles and evaluating programmes of preparation. An extensive literature review and interviews with 49 key informants was used to revise a typology of Domains of Innovative Nursing Roles which the authors had constructed. It also emerged from the key informant interviews that a substantial number of respondents considered the role of the Nurse Practitioner (NP) to be a composite of both specialist and advanced practice. Further analysis indicated that although current preparation for a 'specialist' role would meet many of the outcomes perceived necessary to prepare individuals for the NP role, something 'extra' was seen as a prerequisite for the NP. It is suggested, therefore, that there is a strong case for considering the NP role in terms of 'specialist plus', and that the typology can be helpful in considering the major emphasis within NP roles.

Attitude of Health Personnel↗
PubMed1998

The role of defeat and entrapment (arrested flight) in depression: an exploration of an evolutionary view.

BACKGROUND: The social rank theory of psychopathology suggests that with the evolution of social hierarchies various psychobiological mechanisms became attuned to the success or failure in conflict situations. Specifically, subordinates and those who have lost status are at greater risk of pathology than winners and those of higher status. In this theory concepts of defeat and entrapment are seen to be of special relevance to the study of depression. We outline the role of defeat and entrapment within the social rank theory of depression. METHODS: New self-report measures of entrapment and defeat were developed and used to test predictions of the social rank theory of depression. Both a sample of students and depressed patients were assessed with these new scales and other social rank measures (e.g. social comparison and submissive behaviour). RESULTS: The entrapment and defeat measures were found to have good psychometric properties and significantly correlated with depression. They were also strongly associated with other rank variables. Defeat maintained a strong association with depression even after controlling for hopelessness (r = 0.62), whereas the relationship between hopelessness and depression was substantially reduced when controlling for defeat. Entrapment and defeat added substantially to the explained variance of depression after controlling for the other social rank variables. CONCLUSIONS: Defeat and entrapment appear to be promising variables for the study of depression. These variables may also help to develop linkages between human and animal models of psychopathology.

Adult↗
PubMed1998

Changes in the biocide susceptibility of Staphylococcus epidermidis and Escherichia coli cells associated with rapid attachment to plastic surfaces.

Differences in opacity between wells of a microtitre plate containing different volumes of inoculated growth medium reflected planktonic growth without any contribution from cells attached at the well surface. Simple algebra and a knowledge of the dependence of optical density upon sample path length (volume) for suspensions of differing cell density enables the generation of growth curves for attached populations (biofilms). In this manner, minimum inhibitory concentrations (MICs) were determined at various stages of growth (0-20 h), both for cells growing attached to the bases of the plate wells and, simultaneously, for cells growing in suspension above them. Biocides included cetrimide, polyhexamethylene biguanide, peracetic acid, phenoxyethanol and chloroxylenol. Results, expressed as planktonic:biofilm MIC ratios, showed susceptibility to change, not only as a function of attachment and biofilm formation, but also with respect to the nature of the chemical agent. In some instances, changes in susceptibility greater than twofold occurred immediately on attachment and could occur in the presence of biocide concentrations which exceeded the MIC.

Anti-Infective Agents, Local↗
PubMed1998

Surface-catalysed disinfection of thick Pseudomonas aeruginosa biofilms.

Transition metal catalysts were incorporated into polymers which formed the surface for bacterial attachment and biofilm formation in a constant depth film fermenter (100 microns thickness), flow chamber (about 30 microns thickness) and in batch culture (< 30 microns thickness). The catalysts drive the breakdown of persulphates to reactive oxygen species. When Pseudomonas aeruginosa biofilms were exposed to dilute solutions of potassium monopersulphate (20 micrograms ml-1-1 mg ml-1), significant enhancement of killing was notable for catalyst-containing surfaces over that of controls. The degree of enhancement was greatest for thin films, but was nevertheless significant for the 100 microns thick biofilms. Fluorescence probes and viability staining, in conjunction with laser confocal microscopy, showed that reactive species were generated at the biofilm-substratum interface and killed the biofilm from the inside. Reaction-diffusion limitation now concentrates the active species within the biofilm rather than protecting it, and a diffusion bump is established whereby further treatment agent is drawn to the substratum enabling relatively thick biofilms to be disinfected.

Biofilms↗
PubMed1998

Changes in the strength of attachment of micro-organisms to surfaces following treatment with disinfectants and cleansing agents.

Suspensions of Pseudomonas aeruginosa and Staphylococcus epidermidis, and biofilms established (16 h) on submerged glass and stainless steel (216 2B) coupons, were exposed to sodium hypochlorite (0.02% or 0.015% w/v), Dodigen (0.0015% w/v or 0.0006% w/v), sodium dodecylsulphate (6% w/v or 0.1% w/v) and Tween-80 (6% w/v) for 5 min at 20 degrees C. Survival was assessed by viable counts and blot succession. Biofilm bacteria were significantly less susceptible to these biocides than were planktonic cells, but their attachment to the surfaces was loosened by such treatments. Treatment with the non-ionic surfactant, Tween-80, however, strengthened the attachment of Staph. epidermidis to stainless steel. Such effects on attachment strength, which are species and surface dependent, have profound implications on post-treatment cleansing and possible re-contamination of product in clean-in-place (CIP) systems.

Bacterial Adhesion↗
PubMed1998

Efficient trial designs for studying combination antiretroviral treatments in patients with various resistance profiles.

Selecting antiretroviral therapies for human immunodeficiency virus type 1-infected persons is complicated by the availability of a vast number of potentially useful drug combinations and by extensive variation among patients in their resistance to various drugs. AIDS clinical trials have used designs in which a handful of drug regimens in a few patient classes can be compared. Here is proposed implementation of innovative designs with factorial structure that permit assessment of many treatment arms and patient classes in a single trial; when and how they can be appropriately used are discussed. These designs are efficient, permit systematic investigation of correlations between genetic mutations and in vivo drug resistance, and provide insight into important drug interactions in people that conventional designs are unable to provide. Through creative application of these designs, identification of superior drug combinations and the science of understanding in vivo joint drug dynamics and genotypic resistance will progress at an optimum pace.

Anti-HIV Agents↗
PubMed1998

Performance evaluation of disinfectant formulations using poloxamer-hydrogel biofilm-constructs.

Poloxamer F127 is a di-block co-polymer of polyoxyethylene and polyoxypropylene. Aqueous solutions show thermo-reversible gelation, being liquid at temperatures < 15 degrees C and robust gels at temperatures > 15 degrees C. Chilled poloxamer solutions (30% w/v) were inoculated with approximately 10(4-5) cfu ml-1 of stationary phase cultures of Pseudomonas aeruginosa, Ps. fluorescens, Pantoea agglomerans, Micrococcus luteus, Staphylococcus epidermidis, Bacillus subtilis or Listeria innocua. Drops (200 microliters) of the inoculated poloxamers were placed on stainless steel coupons held in Petri dishes containing moistened cotton wool and incubated at 30 degrees C for 5 h. All strains grew well giving between 10(6-7) cfu ml-1 at 5-6 h. The cultured gels were readily applied to tests of biocide effectiveness as the stainless steel coupons could be removed and flooded with biocide solution for fixed exposure times. Provided that the temperature of the biocide solutions was > 15 degrees C, the integrity of the gels could be maintained during exposure. After exposure, the gels and their supports were removed to separate tubes containing neutralizer solution (< 15 degrees C). The gels rapidly dispersed within 5 min to ensure a complete recovery of the sample population. Biofilm-constructs and cell suspensions (10(7) cfu ml-1) were exposed to four commercial disinfectant formulations, based on hypochlorite, alcohol, hydrogen peroxide and a tenside, at recommended use levels. Cell suspensions, in the presence of bovine serum albumen (BSA; 0.03% w/v), were subject to a > 5-log kill within 5 min while the killing effected against the biofilm-constructs varied between 0.4 and 2-log reductions. The results indicate a high degree of reproducibility between replicate samples, with patterns of susceptibility varying both as a function of organism, biocide type and concentration. The experiments strongly support the view that poloxamer-constructs are suitable for application in trials and testing of disinfectant formulations.

Bacillus subtilis↗
PubMed1998

The use of poloxamer hydrogels for the assessment of biofilm susceptibility towards biocide treatments.

Poloxamer F127 is a non-toxic, di-block copolymer of polyoxyethylene and polyoxypropylene. Aqueous solutions (30% w/v) show thermoreversible gelation, being liquid at temperatures < 15 degrees C and robust gels at temperatures > 15 degrees C. Chilled poloxamer (30% in tryptone soya broth) was mixed with an inoculum of Pseudomonas aeruginosa (10(4) cfu ml-1) and placed as 100 microliters drops onto separate glass cover-slips. These were placed into sealed Petri dishes containing moistened cotton wool and incubated at 35 degrees C. Viable counts could be performed on the poloxamer gels by transfer of the coverslips to diluents at < 15 degrees C. Growth curves in the gels and in liquid batch cultures were indistinguishable from one another with stationary phase cell densities, being approximately 5 x 10(10) cfu ml-1 in each at 16 h. SDS-PAGE of cell envelope preparations showed the poloxamer-grown cells to exhibit a biofilm rather than planktonic phenotype. Susceptibility towards various concentrations of chlorhexidine, iodine and hydrogen peroxide was assessed for 10 min at 35 degrees C for suspensions of broth-grown cells and for incubated poloxamer-gels (1 and 16 h). The gels were immersed in biocide, on their glass supports, before transfer to neutralizer at 10 degrees C where dissolution was complete within 5 min. Further serial dilutions and plate counts were made. While modest decreases in susceptibility towards all biocides were associated with incorporation of the inoculum with the gel (1 h incubation), substantial changes were noted after prolonged incubation and adaptation to a biofilm phenotype (16 h incubation). The gel populations mimic the localized high cell densities observed in biofilms and will also be subject to the same nutrient and chemical gradients as found within natural biofilms. Thermoreversible gelation enables complete recovery of the test inoculum without further trauma. They therefore provide an effective model for assessing biofilm susceptibility towards biocides and would be suitable for screening programmes.

Biofilms↗
PubMed1998

Evolutionary psychopathology: why isn't the mind designed better than it is?

This paper outlines some of the basic issues in evolutionary thinking when applied to psychopathology. It aims to give some background and context to the papers that follow. Particular attention is given to the way evolution is constrained by previous design features, the importance of trade offs between advantages and disadvantages of different traits, the way social dilemmas and conflicts have shaped the evolution of human motivational systems, and the psychology that supports them. The paper concludes with a plea to avoid thinking of evolutionary approaches as a reductionist science, when the focus needs to be on the way evolution theory informs the study of the social-biological interface.

Biological Evolution↗
PubMed1998

The evolved basis and adaptive functions of cognitive distortions.

This paper explores common cognitive distortions from the perspective of evolutionary psychology. It is suggested that cognitive distortions are natural consequences of using fast track defensive algorithms that are sensitive to threat. In various contexts, especially those of threat, humans evolved to think adaptively rather than logically. Hence cognitive distortions are not strictly errors in brain functioning and it can be useful to inform patients that 'negative thinking' may be dysfunctional but is a reflection of basic brain design and not personal irrationality. The evolved nature of cognitive distortions has been implicit in cognitive therapy from its early days (Beck, 1963; Ellis, 1962) but has not been fully articulated in what is now known about evolved mental processes. Many forms of cognitive distortion can be seen to use the (previously) adaptive heuristic of better safe than sorry.

Adaptation, Psychological↗