Biomedical subjects

A Bartlett

Publications and source records attributed to A Bartlett.

At least 19 recordsLinked to original sources

PubMed2005

Acceptability of compulsory powers in the community: the ethical considerations of mental health service users on Supervised Discharge and Guardianship.

OBJECTIVES: To explore mental health service users' views of existing and proposed compulsory powers. DESIGN: A qualitative study employing in-depth interviews. Participants were asked to respond to hypothetical questions regarding the application of compulsory powers under the Mental Health Act 1983 for people other than themselves. SETTING: Community setting in Southeast England. PARTICIPANTS: Mental health service users subject to Supervised Discharge/Guardianship. RESULTS: Participants considered that the use of compulsory powers was justified if there were some ultimate benefit, and if there was evidence of mental health problems, dangerousness, or a lack of insight. However, participants rejected intrusions into their autonomy and privacy. CONCLUSIONS: This paper's participants indicated that the proposed CTO may be unacceptable because it would threaten service users' autonomy. Service users' acceptance of proposed changes is conditional and they emphasised the importance of consent; there is no suggestion that consent will be required for the CTO. The findings also have implications for the exploration of mental health service users' views and how they might contribute to policy, service planning, and research.

Attitude to Health↗

PubMed2004

A comparison of topical formulations for the prevention of human schistosomiasis.

Recently, a dimeticone formulation has been shown to be effective at preventing Schistosoma cercariae infecting skin, while DEET (N,N-diethyl-m-toluamide), a highly effective insecticide, has been shown to have activity against cercariae. Seven formulations, 3 containing DEET, were prepared and applied to excised human skin in Franz cells for 1 h. Schistosoma cercariae were applied for 30 min at 1 and 24 h, and the number that penetrated the skin calculated (n = 9). DEET could not be incorporated into the dimeticone formulation, yet it remained the most effective at preventing cercarial penetration, both 1 and 24 h after application. The ointments that contained DEET did prevent penetration but their mode of action was due to the toxicity of DEET against the cercariae. The persistence of the protection afforded by the dimeticone formulation after washing suggests that the formulation may be interacting with the stratum corneum to prevent cercarial recognition of skin.

Animals↗

PubMed2003

Delayed tail loss during the invasion of human skin by schistosome cercariae.

Schistosomiasis is initiated when cercarial larvae invade human skin. Contrary to long-held assumptions, most cercariae of Schistosoma mansoni do not shed their propulsive tails as they penetrate. Scanning electron microscopy studies and infection experiments with entire human skin and differentiated, stratum corneum-like, human keratinocyte cultures, have shown that most cercarial tails enter the skin along with their bodies. We propose that this behaviour is an adaptive trait linked with concomitant immunity.

Animals↗

PubMed2003

Age-dependent survival and infectivity of Schistosoma mansoni cercariae.

The age dependency of the mortality, spontaneous de-tailing and infectivity of cercariae of Schistosoma mansoni has been determined at 25 degrees C. Infectivity was assessed with respect to stratum corneum-like differentiated human keratinocyte cultures (validated by comparison with fresh human skin samples) and displayed a complex age-dependent pattern. From 1 to 9 h post-emergence cercariae showed a plateau of maximal infectivity (around 90% attachment). Thereafter, infectivity declined. Immediately after release, infectivity at around 60% was significantly lower than the plateau values and this could be an adaptation for spatial dispersal of cercariae. Age-dependent patterns of cercarial mortality and spontaneous de-tailing closely mirrored the infectivity pattern except in relation to the low initial infectivity value. These findings suggest that, at a population level, the age-dependent decline in cercarial infectivity towards human skin is essentially driven by cercarial mortality. The recently described phenomenon of delayed tail loss (DTL) in S. mansoni cercariae infecting human skin is confirmed in the present study. For cercariae aged up to 13.5 h post-emergence, 90% or more of invading cercariae took their tails with them into the keratinocyte culture. The infection dynamics described in this study suggest that diurnally shed S. mansoni cercariae, with peak emergence around mid-day, will have near maximal infectivity towards humans in contact with water through all remaining daylight hours in the tropics.

Age Factors↗

PubMed2003

Penetration of human skin by the cercariae of Schistosoma mansoni: an investigation of the effect of multiple cercarial applications.

It has previously been postulated that L-arginine emitted by penetrating Schistosoma mansoni cercariae serves as an intraspecific signal guiding other cercariae to the penetration site. It was suggested that penetrating in groups offers a selective advantage. If this hypothesis is correct and group penetration at one site on the host offers an advantage, it would follow that at such a site, successive groups of cercariae would be able to penetrate skin in either greater numbers or at a faster rate. This prediction was tested by the use of an in vitro model of cercarial penetration based on the Franz cell and using human skin. It was demonstrated that there was no increase in the percentage of cercariae able to penetrate the skin with subsequent exposures. Consequently, it seems unlikely that the release of L-arginine by cercariae during penetration could have evolved as a specific orientation system based on a selective advantage offered by group penetration.

Animals↗

PubMed2002

The attachment of Schistosoma mansoni cercariae to human skin cells.

Most of our knowledge about the process of penetration of skin, by cercariae of Schistosoma mansoni, has been gained from studies carried out in vivo with laboratory animals. Human skin is significantly different from that of other animals but there are obvious practical difficulties in directly studying attachment and penetration with human skin. Techniques have been developed which enable a 3-dimensional skin equivalent to be grown in tissue culture, made from different types of human skin cells. The aim of the present study was to investigate cercarial interactions with confluent cultures of the individual skin cell types that make up normal human skin and which will be used to construct a multi-component model. Cercariae behaved differently towards the various cell types tested. They responded least to monolayers of endothelial cells and most to primary keratinocytes, derived from human foreskin and differentiated at an air/liquid interface. This study demonstrates, therefore, that cercariae are capable of distinguishing between different types of skin cells and they preferentially attach to differentiated cells which form the epidermis.

Animals↗

PubMed2002

In vitro and in vivo studies on the bioactivity of a ginger (Zingiber officinale) extract towards adult schistosomes and their egg production.

The bioactivity of an ethyl acetate extract of ginger (Zingiber officinale) towards Schistosoma mansoni adult pairs, both cultured in vitro and in vivo in laboratory mice, was investigated by monitoring worm mortality and fecundity. In vitro, a concentration of 200 mg l(-1) of extract killed almost all worms within 24 h. Male worms seemed more susceptible than female under these conditions. Cumulative egg output of surviving worm pairs in vitro was considerably reduced when exposed to the extract. For example, after 4 days of exposure to 50 mg l(-1), cumulative egg output was only 0.38 eggs per worm pair compared with 36.35 for untreated worms. In vivo efficacy of the extract was tested by oral and subcutaneous delivery of 150 mg kg(-1) followed by assessment of worm survival and fecundity. Neither delivery route produced any significant reduction in worm numbers compared with untreated controls. Worm fecundity was assessed in vivo by cumulative egg counts per liver at 55 days post infection with mice treated subcutaneously. Such infections showed egg levels in the liver of about 2000 eggs per worm pair in 55 days, in both treated and control mice, with no significant difference between the two groups. To ensure that density-dependent effects did not confound this analysis, a separate experiment demonstrated no such influence on egg output per worm pair, at intensities between 1 and 23 worms per mouse.

Animals↗

PubMed2002

Antischistosomal bioactivity of isoflavonoids from Millettia thonningii (Leguminosae).

Extracts of the seeds of the leguminous tree Millettia thonningii are molluscicidal and schistosomicidal and contain a mixture of isoflavonoids and 3-phenylcoumarins. Robustic acid and a pure mixture of alpinumisoflavone and dimethylalpinumisoflavone, as characterized by nuclear magnetic resonance, were isolated from a dichloromethane extract. The bioactivity of these compounds against Schistosoma mansoni miracidia, cercariae, and adult worms was tested in vitro. Both robustic acid and the alpinumisoflavone mixture killed cercariae and adult schistosomes in vitro. At sublethal concentrations of the isoflavonoids, reductions in miracidial motility were measured using a video-imaging technique. The inhibition of mitochondrial electron transport at site I by the isolated isoflavonoids was also investigated. The results suggest that robustic acid and at least 1 alpinumisoflavone compound from the dichloromethane extract of the seeds of M. thonniogii are responsible for some of the observed bioactivity of this extract against schistosomes.

Animals↗

PubMed2002

Dimethicone barrier cream prevents infection of human skin by schistosome cercariae: evidence from Franz cell studies.

One approach to the prevention of schistosomiasis is the use of topical formulations to inhibit cercarial penetration of skin. A number of formulations containing either cercaricidal ingredients or components designed to inhibit penetration have been studied, but with variable results. Such studies have rarely considered the persistence of inhibitory effects through time, and to date, there have been no systematic investigations of barrier formulations. The aim of this study was to use Franz cells to investigate the effect of such barrier creams on the penetration of S. mansoni cercariae into human skin. The results show that a single application of a barrier cream based on dimethicone offers a high level of protection against penetration that is sustained for at least 48 hr.

Administration, Topical↗

PubMed2001

Dissecting the cofactor-dependent and independent bindings of PDE4 inhibitors.

Type 4 phosphodiesterases (PDE4s) are metallohydrolases that catalyze the hydrolysis of cAMP to AMP. At the bottom of its active site lie two divalent metal ions in a binuclear motif which are involved in both cAMP binding and catalysis [(2000) Science 288, 1822-1825; (2000) Biochemistry 39, 6449-6458]. Using a SPA-based equilibrium [(3)H]rolipram binding assay, we have determined that Mg(2+), Mn(2+), and Co(2+) all mediated a high-affinity (K(d) between 3 and 8 nM) and near stoichiometric (R)-rolipram binding to PDE4. In their absence, (R)-rolipram binds stoichiometrically to the metal ion-free apoenzyme with a K(d) of approximately 150 nM. The divalent cation dose responses in mediating the high-affinity rolipram/PDE4 interaction mirror their efficacy in catalysis, suggesting that both metal ions of the holoenzyme are involved in mediating the high-affinity (R)-rolipram/PDE4 interaction. The specific rolipram binding to the apo- and holoenzyme is differentially displaced by cAMP, AMP, and other inhibitors, providing a robust tool to dissect the components of metal ion-dependent and independent PDE4/ligand interactions. cAMP binds to the holoenzyme with a K(s) of 1.9 microM and nonproductively to the apoenzyme with a K(d) of 179 microM. In comparison, AMP binds to the holo- and apoenzyme with K(d) values of 7 and 11 mM, respectively. The diminished Mg(2+)-dependent component of AMP binding to PDE4 suggests that most of the Mg(2+)/phosphate interaction in the cAMP/PDE4 complex is disrupted upon the hydrolysis of the cyclic phosphoester bond, leading to the rapid release of AMP.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2001

Cusum analysis of trends in operative selection and conversion rates for laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy (LC) requires a high degree of technical ability, spatial resolution and dexterity. Assessing trainees and competent operators is an important aspect of quality assurance in patient care. Most institutions quote mean conversion rate as a method of comparing operators' performance. The purpose of the present study was to use the technique of cumulative sum (cusum) analysis to determine whether a learning curve phenomenon exists in operators performing LC. METHODS: Data were obtained retrospectively by reviewing the operative records of all patients undergoing elective and acute cholecystectomy for a 30-month period coinciding with the commencement of LC at North Shore Hospital. Patients' age and gender, date and type of operative procedure, duration of operation, and name of operator were recorded. Mean and cusum-transformed data were derived for all operations as well as for four individual operators' performances. RESULTS: Over the study period a total of 614 cholecystectomies was performed, with 85% attempted laparoscopically. A total of 9.8% required conversion to the open technique. Time trend analysis with the cusum technique for all surgeons revealed an inverse relationship between selection rate and conversion rate. Analysis of four individual surgeons revealed three different time trend profiles. CONCLUSION: There was a direct inverse relationship between conversion rate and selection rate, in that careful selection is associated with a low conversion rate. Comparison of individual surgeons' performance showed wide variation, with only one surgeon exhibiting the phenomenon of a learning curve. Contrary to other reports, we found that performance on LC was not always related to operative experience. This highlights the need for a more objective method to analyse operator competence than operator experience alone.

Adolescent↗

PubMed2001

What happens afterwards? A follow-up study of those diverted from custody to hospital in the first 2.5 years of a metropolitan diversion scheme.

BACKGROUND: Court-based psychiatric services aim to identify mentally disordered defendants who require help from Mental Health Services, and attempt to arrange the necessary diversion into health care. This study followed individuals through their hospital stay to assess whether the psychiatric facility to which the individual was transferred was able to manage them, assessed whether the individual benefited from diversion into hospital, and examined how and when the individuals were discharged into the community. METHOD: All those diverted from custody to hospital in the first 2.5 years of a metropolitan diversion scheme were followed through their hospital stay for at least 18 months. RESULTS: Fifty five people were diverted into hospital, from a total of 180 referrals to the court diversion scheme, In excess of 80 per cent were suffering from some form of psychotic disorder. This group had committed relatively serious offences. If appropriately assessed, and appropriate hospital placements are arranged, successful outcome can be achieved for the majority of people diverted from custody to hospital, in terms of improved mental states and a planned discharge. CONCLUSIONS: The services provided by general psychiatric services are able to meet the needs of this group.

Adult↗

PubMed2001

Straight talking: an investigation of the attitudes and practice of psychoanalysts and psychotherapists in relation to gays and lesbians.

BACKGROUND: Early psychodynamic writing on same-gender sexual preference contributed to its pathologisation and an interest in treatment directed at changing sexual orientation. AIMS: To establish the therapeutic approaches taken by contemporary psychotherapists and psychoanalysts to gay and lesbian clients/patients. METHOD: A random sample of individuals listed as working with adults in the British Confederation of Psychotherapists' register were sent postal questionnaires. RESULTS: Data are available from 274 (69%) of 395 questionnaires. Only one of 218 respondents said that he/she was homosexual. One-third said that gay and lesbian patients did have a right to a gay or lesbian therapist. A total of 179 (82% of 218) respondents described work with gay and lesbian clients/patients, and in the majority of cases sexual orientation was an important aspect of the work. CONCLUSIONS: Gays and lesbians seeking psychoanalysis or psychotherapy in the National Health Service or outside it for personal and/or training purposes will be unlikely to find a gay or lesbian therapist if they want one. The British Confederation of Psychotherapists' practitioners take on gay and lesbian clients/patients, although many do not see these social identities as relevant to the therapeutic process. Evidence from this study indicates that such clients/patients may encounter overt or covert bias, including the pathologisation of homosexuality per se.

Attitude of Health Personnel↗

PubMed2001

Co-stimulatory blockade and tolerance induction in transplantation.

Recipients of organ and tissue transplants require lifelong immunosuppression to prevent rejection. Better understanding of the processes culminating in allograft rejection has led to novel approaches to modulating the immune response. Co-stimulatory signals between antigen-presenting and -responding cells are essential for a normal alloimmune response, and blockade of these pathways during initial graft-host interaction may be used to ameliorate or prevent a destructive response from proceeding. A large number of experimental studies now support this concept, and early clinical trials have been initiated. Despite some early difficulties and many unanswered questions, co-stimulatory blockade has major potential as a future immune-modulating mechanism for use in clinical transplantation.

Animals↗

PubMed2001

Psychotherapists' approaches to gay and lesbian patients/clients: a qualitative study.

We used qualitative research methods to examine the core issues relating to the approaches of psychodynamic and psychoanalytic psychotherapists to gay and lesbian patients and clients. The paper begins with a review of the psychoanalytic approaches to gay and lesbian sexuality and continues with material of a clinical nature, providing information about the experience of lesbians and gay men in psychotherapy. It also explores the attitudes of therapists towards gay and lesbian sexuality by discussing a range of psychoanalytic theories and their application to clinical work with patients and clients.

Attitude of Health Personnel↗

PubMed2000

Conformational difference between PDE4 apoenzyme and holoenzyme.

The type 4 cAMP-specific phosphodiesterases (PDE4s) are Mg(2+)-dependent hydrolases that catalyze the hydrolysis of 3', 5'-cAMP to AMP. Previous studies indicate that PDE4 exists in two conformations that bind the inhibitor rolipram with affinities differing by more than 100-fold. Here we report that these two conformations are the consequence of PDE4 binding to its metal cofactor such as Mg(2+). Using a fluorescence resonance energy transfer (FRET)-based equilibrium binding assay, we identified that L-791,760, a fluorescent inhibitor, binds to the apoenzyme (free enzyme) and the holoenzyme (enzyme bound to Mg(2+)) with comparable affinities (K(d) approximately 30 nM). By measuring the displacement of the bound L-791,760, we have also identified that other inhibitors bind differentially with the apoenzyme and the holoenzyme depending upon their structure. CDP-840, SB-207499, and RP-73401 bind preferentially to the holoenzyme. The conformational-sensitive inhibitor (R)-rolipram binds to the holoenzyme and apoenzyme with affinities (K(d)) of 5 and 300 nM, respectively. In contrast to its high affinity (K(d) approximately 2 microM) and active holoenzyme complex, cAMP binds to the apoenzyme nonproductively with a reduced affinity (K(d) approximately 170 microM). These results demonstrate that cofactor binding to PDE4 is responsible for eliciting its high-affinity interaction with cAMP and the activation of catalysis.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2000

The infection of human skin by schistosome cercariae: studies using Franz cells.

Franz cells (2-chambered, air/fluid phase static diffusion devices, previously used for the study of drugs across viable human skin) are utilized for the first time to investigate the process of infection of human skin by Schistosoma mansoni cercariae. Skin obtained from cosmetic surgery sources was used in the Franz cells to describe the temporal dynamics of the early interaction of cercariae with skin. At 38 degrees C, about 50% of cercariae applied in water to the epidermal surface of the skin were irreversibly attached within 1 min and after 5 min about 85%, were similarly irrecoverable. The technique also provides the means of following the early penetration path of cercariae by histological methods. Franz cell results on the dynamics of attachment/early penetration have been compared with those obtained using artificial skin equivalents and non-human mammalian skin models in the context of the physical and chemical differences between these systems and viable human skin. It is concluded that Franz cells provide a convenient system for directly investigating the early phases of S. mansoni cercariae interaction with human skin.

Animals↗

PubMed2000

The kinetics of CD154 (CD40L) expression in peripheral blood mononuclear cells of healthy subjects in liver allograft recipients and X-linked hyper-IgM syndrome.

UNLABELLED: The costimulatory pathways play a key role in T cell activation during allograft rejection (AR). Inhibition of the T cell costimulatory molecule CD154 (CD40 ligand) has been effective in producing long-term allograft survival in rodents and non-human primates. The role of the CD40-CD154 pathway in human orthotopic liver transplantation (OLT) has not been examined. AIM: To describe the patterns of CD154, CD69 and CD152 (CTLA4) expression in OLT recipients and to determine their temporal relationship to AR. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from 15 OLT allograft recipients just prior to and for seven consecutive days postoperatively. Gene and protein expression of CD154, CD69 and CD154 were examined by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry (FC), respectively. RESULTS: FC failed to demonstrate an up-regulation of CD154 and CD152 protein expression during the first postoperative week. Intracellular FC did not increase the sensitivity. There was an increased level of CD3+ CD8+ T cells expressing CD69 at the time of rejection compared to that on day 0. RT-PCR demonstrated a sporadic expression of CD154 and CD69 mRNA, with no correlation to episodes of acute cellular rejection. In vitro stimulation of PBMCs revealed an impaired up-regulation of CD154 in patients receiving conventional immunosuppression compared to healthy controls. The assays were validated using positive and negative controls, including a family with X-linked hyper-IgM syndrome. CONCLUSION: We found no evidence of spontaneous CD154 gene or protein expression in PBMCs associated with acute rejection episodes following OLT. Immunosuppression resulted in impaired responses to ex vivo stimulation. Lymphocyte costimulatory pathways play a critical role in mediating acute allograft rejection. However, we found no evidence of spontaneous CD154 gene or protein expression in PBMCs associated with acute rejection episodes following OLT. Furthermore, stimulation in vitro resulted in less up-regulation of CD154 than for healthy controls.

Abatacept↗