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Biomedical subjects

P Gilbert

Publications and source records attributed to P Gilbert.

At least 55 records · Page 3Linked to original sources
PubMed2001

Assessment of resistance towards biocides following the attachment of micro-organisms to, and growth on, surfaces.

AIMS: To develop a rapid method for the assessment of biocidal activity directed towards intact biofilms. METHODS AND RESULTS: Escherichia coli and Staphylococcus epidermidis were cultured for up to 48 h within 96-well microtitre plates. The planktonic phase was removed and the wells rinsed. Residual biofilms were exposed to various concentrations of chloroxylenol, peracetic acid, polyhexamethylene biguanide (PHMB), cetrimide or phenoxyethanol for 1 h. At 15-min intervals, biocide was removed, and the wells washed in neutraliser and filled with volumes of fresh medium. Re-growth of the cultures was monitored during incubation at 35 degrees C in the plate reader. Times taken for the treated wells to re-grow to fixed endpoints were determined and related to numbers of surviving cells. Time--survival curves were constructed and the survival of the attached bacteria, following exposure to the agents for 30 min, interpolated for each biocide concentration. Log--log plots of these survival data and biocide concentration were constructed, and linear regression analysis performed in order to (i) calculate concentration exponents and (ii) compare the effectiveness of the biocides between variously aged biofilm and planktonic cells. From such analyses iso-effective concentrations of biocide (95% kill in 30 min) were calculated and expressed as planktonic : biofilm indices (PBI). CONCLUSION: PBI varied between 1.02 and 0.02, were relatively unaffected by age of the biofilms but differed significantly between organism and biocide. Notably those compounds with the higher activity against planktonic bacteria (PHMB and peracetic acid) were most prone to a biofilm effect but remained the most effective of the agents selected. SIGNIFICANCE AND IMPACT OF THE STUDY: The endpoint method proved robust, enabled the bactericidal effects of the biocides to be assessed against in-situ biofilms, and was suitable for routine screening applications.

Bacterial Adhesion↗
PubMed2001

Evolutionary approaches to psychopathology: the role of natural defences.

OBJECTIVE: Psychoanalytic theories of the mind emerged in the immediate post-Darwinian era of the 1880s and 1890s. Since that time much has changed in both psychoanalytic and evolutionary theorizing. This paper explores recent evolutionary thinking on psychopathology. METHOD: Relevant literature was reviewed. RESULTS: This paper outlines some of the common behavioural defence mechanisms and then explores ways in which they are represented in various disorders, with a focus on depression. This paper suggests that 'symptoms' can be related to the activation of evolved defence mechanisms to respond to losses and threats. Such will involve, for example, anxious arousal and heightened vigilance and attention to the threat, with the type of defence (e.g. fight, flight, submit, help seeking) being mirrored in particular symptom presentations. CONCLUSION: Defences can become pathological when they are too easily aroused or prolonged, are arrested (aroused but not expressed) and/or ineffective.

Adaptation, Psychological↗
PubMed2001

Identification of human immunodeficiency virus type 1 subtype C Gag-, Tat-, Rev-, and Nef-specific elispot-based cytotoxic T-lymphocyte responses for AIDS vaccine design.

The most severe human immunodeficiency virus type 1 (HIV-1) epidemic is occurring in southern Africa. It is caused by HIV-1 subtype C (HIV-1C). In this study we present the identification and analysis of cumulative cytotoxic T-lymphocyte (CTL) responses in the southern African country of Botswana. CTLs were shown to be an important component of the immune response to control HIV-1 infection. The definition of optimal and dominant epitopes across the HIV-1C genome that are targeted by CTL is critical for vaccine design. The characteristics of the predominant virus that causes the HIV-1 epidemic in a certain geographic area and also the genetic background of the population, through the distribution of common HLA class I alleles, might impact dominant CTL responses in the vaccinee and in the general population. The enzyme-linked immunospot (Elispot) gamma interferon assay has recently been shown to be a reliable tool to map optimal CTL epitopes, correlating well with other methods, such as intracellular staining, tetramer staining, and the classical chromium release assay. Using Elispot with overlapping synthetic peptides across Gag, Tat, Rev, and Nef, we analyzed HIV-1C-specific CTL responses of HIV-1-infected blood donors. Profiles of cumulative Elispot-based CTL responses combined with diversity and sequence consensus data provide an additional characterization of immunodominant regions across the HIV-1C genome. Results of the study suggest that the construction of a poly-epitope subtype-specific HIV-1 vaccine that includes multiple copies of immunodominant CTL epitopes across the viral genome, derived from predominant HIV-1 viruses, might be a logical approach to the design of a vaccine against AIDS.

AIDS Vaccines↗
PubMed2001

Endothelium-derived endothelin-1 reduces cerebral artery sensitivity to nitric oxide by a protein kinase C-independent pathway.

BACKGROUND AND PURPOSE: Nitric oxide (NO) reduces endothelin-1 (ET-1) production and blunts ET-1 dependent vasoconstriction. The direct effects of smooth muscle ET(A) receptor stimulation on NO-mediated relaxation are unknown. We hypothesized that endothelium-derived ET-1 regulates vascular tone by reducing smooth muscle sensitivity to NO, possibly through activation of protein kinase C (PKC). METHODS: Rings of rabbit middle cerebral artery were mounted on microvessel myographs to measure isometric tension. Dose-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP; an NO donor) were obtained with or without ET-1 receptor blockade. Experiments were performed in the presence of indomethacin (10 micromol/L). Results are expressed as mean+/-SEM. RESULTS: In depolarized conditions (40 mmol/L KCl physiological solution), ACh-induced relaxation was entirely NO-dependent, as indicated by its suppression by N(omega)-nitro-L-arginine (P<0.05). Arterial sensitivity (pD(2)) to ACh (6.32+/-0.11, n=6) was increased (P<0.05) to 6.77+/-0.10 (n=6) by BQ123 (ET(A) receptor antagonist, 5 micromol/L) but not by BQ788 (ET(B) receptor antagonist, 5 micromol/L; 6.08+/-0.22, n=5). Consistent with this finding, blockade of ET(A) receptors increased (P<0.05) vascular sensitivity to SNP (6.95+/-0.10, n=8), whereas BQ788 had no influence on arterial sensitivity to SNP (6.17+/-0.07, n=7) compared with control (6.43+/-0.13, n=11). In denuded arteries, the sensitivity to SNP (7.10+/-0.08, n=8) was reduced by exogenous ET-1 (6.51+/-0.35, n=7, P<0.05). Chelerythrine, a PKC inhibitor, did not alter smooth muscle sensitivity to NO, whereas phorbol 12-myristate 13-acetate, a PKC activator, strongly increased it. CONCLUSIONS: Blockade of ET(A) but not ET(B) receptors sensitizes vascular smooth muscle to exogenous and endothelium-derived NO. This suggests that ET-1 regulates smooth muscle sensitivity to NO by a PKC-independent pathway. This represents an alternative pathway by which NO and ET-1 interact to regulate vascular tone.

Animals↗
PubMed2001

Acne: a biopsychosocial and evolutionary perspective with a focus on shame.

PURPOSE: Hypotheses regarding the psychological factors implicated in the development and maintenance of acne first emerged in the middle of the eighteenth century. However, the psychodermatological literature from this date relating to acne has variously been described as confusing, overly prone to conjecture and, in particular, atheoretical. The current paper has two key objectives; first, to present a biopsychosocial model of acne development and maintenance and, secondly, to understand the psychosocial strain imposed by acne from an evolutionary perspective with a particular emphasis on body shame reactions. METHODS: The psychodermatological literature relating to acne is reviewed with the data analysed for potential biopsychosocial interactions and shame eliciting responses. RESULTS: The review indicates that acne can be reconceptualized as a biopsychosocial phenomena which, in turn, provides the field with innovative hypotheses for empirical inquiry and the potential for expanding and evaluating treatment options. The evolutionary analysis illustrates that acne provides the potential for distressing body shame reactions due to the skin disease's potential for damaging self-other evaluations of attractiveness. CONCLUSIONS: Acne has tended to be viewed as a minor dermatological complaint which imposes minimal psychological distress upon sufferers. The paper concludes that acne has the ability to elicit in some sufferers significant mental health concerns due to a heightened sense of shame relating to appearance.

Journal Article↗
PubMed2000

The power and omnipotence of voices: subordination and entrapment by voices and significant others.

BACKGROUND: Cognitive therapy for psychotic symptoms often embraces self-evaluative beliefs (e.g. self-worth) but whether and how such beliefs are related to delusions remains uncertain. In previous research we demonstrated that distress arising from voices was linked to beliefs about voices and not voice content alone. In this study we examine whether the relationship with the voice is a paradigm of social relationships in general, using a new framework of social cognition, 'ranking' theory. METHOD: In a sample of 59 voice hearers, measures of power and social rank difference between voice and voice hearer are taken in addition to parallel measures of power and rank in wider social relationships. RESULTS: As predicted, subordination to voices was closely linked to subordination and marginalization in other social relationships. This was not the result of a mood-linked appraisal. Distress arising from voices was linked not to voice characteristics but social and interpersonal cognition. CONCLUSION: This study suggests that the power imbalance between the individual and his persecutor(s) may have origins in an appraisal by the individual of his social rank and sense of group identification and belonging. The results also raise the possibility that the appraisal of voice frequency and volume are the result of the appraisal of voices' rank and power. Theoretical and novel treatment implications are discussed.

Adult↗
PubMed2000

Expression of the multiple antibiotic resistance operon (mar) during growth of Escherichia coli as a biofilm.

The multiple antibiotic resistance (mar) operon is a global regulator controlling the expression of various genes in Escherichia coli which constitutes the mar regulon. Upregulation of mar leads to a multi-drug resistant phenotype, which includes resistance towards structurally unrelated antibiotics, organic solvents and the disinfectant pine oil. Biofilms also display similar decreases in susceptibility to antimicrobial agents. A marOII-lacZ fusion strain (SPC105) of E. coli was used to monitor mar expression under various growth conditions including batch, continuous and biofilm culture. In chemically-defined media (CDM), mar expression was maximal in mid-log and declined in the stationary phase. Conversely, in rich media (Luria-Bertani broth), minimal expression in mid-log was followed by an increase in the stationary phase. In continuous culture, expression was inversely related to specific growth rate (mu = 0.05-0.4 h-1). LacZ expression by the marOII-lacZ fusion was generally low within the total biofilm population and equivalent to that of stationary phase cultures grown in batch culture. When the expression of mar in CDM batch culture was compared with that in biofilm populations, beta-galactosidase activity was generally higher throughout batch culture than in the attached population. Overall, these results suggest that while mar expression will be greatest within the depths of a biofilm where growth rates are suppressed, its probable induction within biofilms cannot explain the elevated levels of antibiotic resistance observed.

Bacterial Proteins↗
PubMed2000

The effect of a rapid change in availability of epidural analgesia on the cesarean delivery rate: a meta-analysis.

OBJECTIVE: This study was undertaken to quantitatively estimate the effect of a rapid introduction or withdrawal of on-demand epidural analgesia on the cesarean delivery rate. STUDY DESIGN: MEDLINE and meeting abstracts were searched for studies reporting the cesarean delivery rate immediately before and after a rapid change in the availability of epidural analgesia. Nine studies reporting data on 37,753 patients were selected. Meta-analysis was performed to estimate the means and 95% confidence intervals for the changes in rates of total cesarean deliveries, cesarean deliveries among nulliparous women, cesarean deliveries for dystocia, and operative vaginal deliveries. RESULTS: There was no significant change in the overall cesarean delivery rate with an increase in the availability of epidural analgesia. Similarly, the rates of cesarean deliveries among nulliparous patients, of cesarean deliveries for dystocia, and of operative vaginal deliveries did not significantly differ between periods of high and low epidural analgesia availability. CONCLUSION: A rapid change in the availability of epidural analgesia is not associated with any increase in the cesarean delivery rate.

Analgesia, Epidural↗
PubMed2000

An evaluation of the potential of the multiple antibiotic resistance operon (mar) and the multidrug efflux pump acrAB to moderate resistance towards ciprofloxacin in Escherichia coli biofilms.

The chromosomal multiple antibiotic resistance operon, mar, is widely represented amongst Gram-negative bacteria and has been implicated in resistance towards oxidative stress agents, organic solvents and a large number of structurally unrelated antimicrobial agents. The major mechanism associated with such increased resistance is an upregulation of the efflux pump acrAB. Growth as a biofilm is often associated with similar generalized reductions in susceptibility to inimical agents. Escherichia coli K12 (AG100), an isogenic mutant of AG100 constitutive for mar expression (AG102) and an isolate deleted of the mar locus (MCH164) were grown as biofilms in cellulose-fibre depth filters and perfused with a simple salts, minimal medium (CDM) over 120 h. Biofilms were exposed to various concentrations of ciprofloxacin (0.004, 0.015 and 0.1 mg/L) for 42 h. The numbers of viable cells within the perfusate and within the biofilm were estimated throughout. Whereas no differences were seen between the wild-type and mar-deleted isolates, that constitutive for mar displayed reduced susceptibility to ciprofloxacin at concentrations of 0.004 mg/L (MIC for AG100 was 0.0052 mg/L). Similar antibiotic perfusion experiments were conducted using isolates in which the efflux pump acrAB was either deleted (AG100-A) or constitutively expressed (AG100-B). Exposure of AG100-A biofilms to ciprofloxacin at 0.004 and 0.1 mg/L showed similar susceptibilities to those seen in the wild-type (AG100) and mar-deleted (MCH164) isolates and suggested that acrAB was not induced within the attached population. On the other hand, constitutive expression of acrAB (AG100-B) protected biofilms against the lower concentration of ciprofloxacin used (0.004 mg/L). This protection was again lost at concentrations of 0.1 mg/L. Overall, these results show that ciprofloxacin resistance in biofilms is not mediated by the upregulation of the mar or acrAB operons.

Ampicillin↗
PubMed2000

Menstruation in schoolgirls--1: The normal menarche.

The mean age for onset of menstruation (menarche) is 12.8 years. Many schools teach girls about puberty and menstruation and prepare them for the menarche. The school nurse has a valuable part to play in all aspects of menstruation in schoolgirls, psychological as well as physical. The early periods may be irregular and vary markedly in the amount of blood loss. It can take up a year or more for a steady pattern to develop. Dysmenhorrhoea may occur, which may be mild or of the severe spasmodic type. Premenstrual tension syndrome is less common in schoolgirls. Girls should be taught about the importance of hygiene, especially if tampons are used.

Adolescent↗
PubMed1999

Emerging recombinant human immunodeficiency viruses: uneven representation of the envelope V3 region.

OBJECTIVE: To determine whether the envelope V3 region from HIV-1 subtypes A, C or D had the same probability of being present in intersubtype recombinant genomes. MATERIALS AND METHODS: The envelope C2-C5 and the gag p24-p7 regions from one hundred infants infected perinatally in Tanzania were compared using phylogenetic and recombination analysis. Exact binomial and Fisher's exact tests were used to assess if various genomic regions were more likely to be overrepresented in intersubtype recombinants. RESULTS: Of one hundred HIV-1 positive infants analyzed, twenty-two (22%) showed exclusively subtype A sequence in gag and env. Subtype C accounted for twenty-two infants (22%) whereas nineteen infants (19%) were infected by HIV-1 subtype D. Intersubtype recombinant genomes accounted for thirty-seven infections (37%). The V3 region from subtype A was found in all fifteen A-D recombinants (P = 0.00003) and the V3 region from subtype C was found in all twelve C-D recombinants (P = 0.0002). Conversely, subtype D gag sequences were preferentially represented in the gag of A-D recombinants (P = 0.0003) as well as C-D recombinants (P = 0.002). In A-D recombinants, the V3 region of subtype A was generally surrounded by subtype A C3-C5 sequences. In contrast, the V3 region from subtype C was surrounded by subtype D C3-C5 sequences in C-D recombinants. Significant differences were not found in the number of subtype A or subtype C sequences in A-C recombinants. CONCLUSION: We have shown that several recombinant HIV-1 viruses have been generated and efficiently transmitted to infants in Tanzania. The recombination patterns showed that the V3 region of subtypes A or C was always selected in A-D and C-D recombinants. This selection suggests that the fitness of subtype D-V3 in perinatal transmission may be reduced with respect to V3 from subtype A and/or subtype C. The elevated number of recombinants transmitted perinatally suggests that co-infection or super-infection by two HIV-1 subtypes is not uncommon in this population.

Amino Acid Sequence↗
PubMed1999

A murine model of myocardial microvascular thrombosis.

Disorders of hemostasis lead to vascular pathology. Endothelium-derived gene products play a critical role in the formation and degradation of fibrin. We sought to characterize the importance of these locally produced factors in the formation of fibrin in the cardiac macrovasculature and microvasculature. This study used mice with modifications of the thrombomodulin (TM) gene, the tissue-type plasminogen activator (tPA) gene, and the urokinase-type plasminogen activator (uPA) gene. The results revealed that tPA played the most important role in local regulation of fibrin deposition in the heart, with lesser contributions by TM and uPA (least significant). Moreover, a synergistic relationship in fibrin formation existed in mice with concomitant modifications of tPA and TM, resulting in myocardial necrosis and depressed cardiac function. The data were fit to a statistical model that may offer a foundation for examination of hemostasis-regulating gene interactions.

Animals↗