Biomedical subjects
Publications and source records attributed to S Harrison.
A telephone survey of primary care groups and trusts revealed that visits to community groups are the most favoured form of public involvement. There was some evidence of plans having been changed in response to public involvement. It is too early to say whether PCG/Ts will be more successful in involving the public in planning care than health authorities.
Recently, the cannabinoid (CB) receptor agonist anandamide (AEA) has been shown to excite perivascular terminals of primary sensory neurons via activation of the vanilloid receptor-1 (VR-1). To determine whether AEA stimulates central terminals of these neurons, via VR-1 activation, we studied the release of calcitonin gene-related peptide (CGRP)- and substance P (SP)-like immunoreactivities (LI) from slices of rat dorsal spinal cord. Mobilization of Ca(2+) in rat dorsal root ganglion (DRG) neurons in culture was also studied. AEA (0.1-10 micrometer) increased the outflow of CGRP-LI and SP-LI from slices of the rat dorsal spinal cord in a Ca(2+)-dependent manner and increased [Ca(2+)](i) in capsaicin-sensitive cultured DRG neurons. Both effects of AEA were abolished by capsaicin pretreatment and by the VR-1 antagonist capsazepine but not affected by the CB receptor antagonists AM281 or AM630. Both neuropeptide release and Ca(2+) mobilization induced by electrical field stimulation (EFS) were inhibited by a low concentration of AEA (10 nm). Inhibition by AEA of EFS-induced responses was reversed by AM281 and AM630, but was not affected by capsazepine. Results indicate that stimulation of VR-1 with high concentrations of AEA excites central terminals of capsaicin-sensitive DRG neurons, thus causing neuropeptide release in the dorsal spinal cord. This novel activity opposes the CB receptor-mediated inhibitory action of low concentrations AEA. However, only if large amounts of endogenous AEA could be produced at the level of the dorsal spinal cord, they may not inhibit, but rather activate, nociceptive sensory neurons.
This paper reports on a trial of vaginal products that were distributed and used by 131 women and 21 men in south west Uganda. It focuses specifically upon the issue of female control in heterosexual relationships and examines whether methods which are ostensibly under women's control, will in practice give women greater control of their sexual health. Participants were invited to select two from a range of vaginal products that included the female condom, contraceptive sponge, film, tablets, foam and gel, and use each for five weeks and their favourite product for a further three months. They were interviewed up to seven times over a five-month period. Although the women perceived that a major advantage of the products (with the exception of the female condom) was that they could be used secretly, less than 40% were using the products without their partner's knowledge after one week and this proportion declined over time with only 22% using the products secretly after ten weeks. In the main male partners were told as women felt it their duty to inform them. In general the women were very much more positive about the products than they were about the male condom, as were the men. A contributory factor to their popularity among women was the greater control they gave them. Even though, use of these products in practice often involved negotiation with male partners, the fact that use was contingent on women's action was empowering and increased somewhat their ability to control their sexual health.
This article provides a brief overview of the history of substance P from its discovery in the 1930s to the present day. The development of substance P receptor agonists and antagonists, and more recently the employment of transgenic mice, provide a framework to explore the functional role of substance P. Chronic inflammation and pain are associated with a number of diseases, and it has been proposed that substance P, released from primary afferent nerve endings play a role in these conditions. Recent developments with substance P antagonists have demonstrated the importance of substance P in several models of disease that span from asthma to chronic bronchitis; from cystitis, inflammatory bowel disease to migraine; emesis, depression, pain and seizures. Advancements in the knowledge of the role of substance P, its agonists and antagonists could provide clinical solutions for a variety of chronic inflammatory conditions.
The experimental group consisted of men from 81 couples waiting for in vitro fertilization (IVF), about half of whom had sperm dysfunction defined by a negative post-coital test. A diagnostic semen sample was subjected to a hamster oocyte penetration test (HOPT) after stimulation of the acrosome reaction with A23187 +/- pentoxifylline and to computerized sperm motility measurements (CASA) as well as conventional semen analysis according to the WHO protocol. Logistic regression was used to identify parameters that predicted the probability of achieving four or more viable embryos at IVF among the 65 couples from whom four or more oocytes were collected. The number of oocytes available and whether the woman had previously been pregnant (ever pregnant) were important factors but once these had been taken into account a number of sperm parameters had additional predictive power. The most useful of these were the percentage sperm static (CASA) or the percent sperm progressively motile (conventional semen analysis) in the Percoll preparation. A model incorporating the number of oocytes collected, ever pregnant and percentage sperm static achieved 85% correct prediction of outcome in the experimental dataset but only 62% correct prediction in an independent set of 280 IVF cycles. The percentage of hamster oocytes penetrated was a significant predictor but had no advantage over simple motility measurements. The results illustrate the difficulty of basing a prognosis for achieving satisfactory fertilization in IVF on the properties of spermatozoa.
The endogenous cannabinoid receptor ligand, anandamide (AEA), is a full agonist of the vanilloid receptor type 1 (VR1) for capsaicin. Here, we demonstrate that the potency and efficacy of AEA at VR1 receptors can be significantly increased by the concomitant activation of protein kinase A (PKA). In human embryonic kidney (HEK) cells over-expressing human VR1, AEA induces a rise in cytosolic Ca(2+) concentration that is mediated by this receptor. The EC(50) for this effect was decreased five-fold in the presence of forskolin (FRSK, 1-5 microM) or the cAMP analogue, 8-Br-cAMP (10-100 microM). The effects of 8-Br-cAMP and FRSK were blocked by a selective PKA inhibitor. The FRSK (10 nM) also potently enhanced the sensory neurone- and VR1-mediated constriction by AEA of isolated guinea-pig bronchi, and this effect was abolished by a PKA inhibitor. In rat dorsal root ganglia slices, AEA-induced release of substance P, an effect mediated by VR1 activation, was enhanced three-fold by FRSK (10 nM). Thus, the ability of AEA to stimulate sensory VR1, with subsequent neuropeptide release, appears to be regulated by the state of activation of PKA. This observation supports the hypothesis that endogenous AEA might stimulate VR1 under certain pathophysiological conditions.
Looks at some of the issues raised by patients' involvment in the research process. Uses the example of a service users' advisory group established as part of a diabetes service evaluation in the north of England. Key conclusions were: a precise role for the group should be specified at the outset; genuine user involvement is needed; wide and accurate representation of all relevant groups in society is essential; and, researchers must approach users with open minds with a view to shared decision making rather than control.
Culturing of pharyngeal swabs for Neisseria meningitidis is an important clinical and epidemiological tool. Routine methods include direct plating onto solid medium or later plating in the laboratory. A comparison of these methods used with 490 high school students found a significantly higher carriage rate with direct plating (11.8 versus 6.1%; P < 0.001).
Two alleles of the Drosophila melanogaster Rfc4 (DmRfc4) gene, which encodes subunit 4 of the replication factor C (RFC) complex, cause striking defects in mitotic chromosome cohesion and condensation. These mutations produce larval phenotypes consistent with a role in DNA replication but also result in mitotic chromosomal defects appearing either as premature chromosome condensation-like or precocious sister chromatid separation figures. Though the DmRFC4 protein localizes to all replicating nuclei, it is dispersed from chromatin in mitosis. Thus the mitotic defects appear not to be the result of a direct role for RFC4 in chromosome structure. We also show that the mitotic defects in these two DmRfc4 alleles are the result of aberrant checkpoint control in response to DNA replication inhibition or damage to chromosomes. Not all surveillance function is compromised in these mutants, as the kinetochore attachment checkpoint is operative. Intriguingly, metaphase delay is frequently observed with the more severe of the two alleles, indicating that subsequent chromosome segregation may be inhibited. This is the first demonstration that subunit 4 of RFC functions in checkpoint control in any organism, and our findings additionally emphasize the conserved nature of RFC's involvement in checkpoint control in multicellular eukaryotes.
OBJECTIVES: 1) To compare two measurement models of the BDI in chronic pain sufferers to see which provides the better fit; 2) to assess whether model fit differs for a facial pain sample compared to a sample of pain sufferers attending a multidisciplinary pain clinic; and 3) to establish which affective and somatic sub-scales of the BDI could be used in chronic pain research. DESIGN: Two groups of chronic pain sufferers, a facial pain group, and a group attending a multidisciplinary pain clinic completed self-report questionnaires on pain (Multidimensional Pain Inventory), depression (BDI), and measures of anxiety and depression-related pain cognitions (the Spielberger State-Trait Anxiety Inventory and the Pain Cognitions Questionnaire). The measurement models of the BDI were tested using LISREL structural equation modelling and their construct validity examined using partial correlation analysis. METHOD: A total of 173 people attending a multidisciplinary pain clinic and 157 patients attending a facial pain clinic completed self-report measures of pain and mood prior to their respective clinical consultations. RESULTS: The model offered by Novy et al. (containing one affective factor 'Negative-attitude suicide' and two somatic factors 'Performance difficulty' and 'Physiological manifestations') fitted both pain groups better than the model offered by Williams and Richardson (containing one affective factor 'Self-reproach', one somatic factor 'Somatic disturbance' and one factor with a mixture of both affective and somatic items 'Sadness about health'). However, when the factors were allowed to correlate in the latter model, both models were broadly equivalent. CONCLUSIONS: The two measurement models adequately fitted data in both pain samples when the factors were allowed to intercorrelate in the Williams and Richardson model. Both the affective scales offered by both models could be used in future research, although the somatic factor offered by the Williams and Richardson model offered much higher levels of internal reliability than either of those offered in the Novy et al. model. The findings are discussed in relation to the issue of depression in chronic pain.
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We present and analyze a simple three-patch host-parasitoid model where population growth is discrete. The model gives solutions that are qualitatively similar to the stable large-amplitude patterns in space found in reaction-diffusion theory. In the context of host-parasitoid interactions, the large-amplitude portions of the solution can be thought of as spatially localized host population outbreaks. Here, we show that the biological requirements for localized population outbreaks in a discrete world are identical to those found in reaction- diffusion theory. Furthermore, the model conveniently allows investigation into the robustness of these population outbreaks under the influence of density-dependent dispersal behavior. We find that localized population outbreaks in space can still occur with modest amounts of pursuit and aggregative behavior by parasitoids. We end by showing that evidence from a real host-parasitoid system is consistent with the predictions of the model.
We have investigated the ability of protease-activated receptor-1 (PAR-1), PAR-2, PAR-3 and PAR-4 agonists to induce contractile responses in isolated guinea-pig gallbladder. Thrombin, trypsin, mouse PAR-1 activating (SFLLRN-NH(2)) peptide, and mouse PAR-2 activating (SLIGRL-NH(2)) and human PAR-2 activating (SLIGKV-NH(2)) peptides produced a concentration-dependent contractile response. Mouse PAR-4 activating (GYPGKF-NH(2)) peptide, the mouse PAR-1 reverse (NRLLFS-NH(2)) peptide, the mouse PAR-2 reverse (LRGILS-NH(2)) and human PAR-2 reverse (VKGILS-NH(2)) peptides caused negligible contractile responses at the highest concentrations tested. An additive effect was observed following the contractile response induced by either trypsin or thrombin, with the addition of a different PAR agonist (SFLLRN-NH(2) and SLIGRL-NH(2), respectively). Desensitization to PAR-2 activating peptide attenuated the response to trypsin but failed to attenuate the response to PAR-1 agonists, and conversely desensitization to PAR-1 attenuated the response to thrombin but failed to alter contractile responses to PAR-2 agonists. The contractile responses produced by thrombin, trypsin, SFLLRN-NH(2) and SLIGRL-NH(2) were markedly reduced in the presence of the cyclo-oxygenase inhibitor, indomethacin, whilst the small contractile response produced by NRLLFS-NH(2) and LRGILS-NH(2) were insensitive to indomethacin. The contractile responses to thrombin, trypsin, SFLLRN-NH(2) and SLIGRL-NH(2) were unaffected by the presence of: the non-selective muscarinic antagonist, atropine; the nitric oxide synthase inhibitor, L-NAME; the sodium channel blocker, tetrodotoxin; the combination of selective tachykinin NK(1) and NK(2) receptor antagonists, (S)-1-[2-[3-(3,4-dichlorphenyl)-1 (3-isopropoxyphenylacetyl) piperidin-3-yl] ethyl]-4-phenyl-1 azaniabicyclo [2.2.2] octane chloride (SR140333) and (S)-N-methyl-N-[4-acetylamino-4-phenylpiperidino-2-(3, 4-dichlorophenyl)-butyl] benzamide (SR48968), respectively. The results indicate that PAR-1 and PAR-2 activation causes contractile responses in the guinea-pig gallbladder, an effect that is mediated principally by prostanoid release, and is independent of neural mechanisms.
This paper reports the experience of a single pilot in total primary care purchasing (TPP) between 1995 and 1997. The article's structure is based on a framework created from the seven original objectives of the pilot and 12 themes emerging from qualitative data analysis. Data are mainly drawn from interviews with participants. Interesting and useful findings emerge. For example, the TPP was able to build positive relationships with other local actors and amongst its GPs, though these did not necessarily lead to agreement or compliance. The TPP undertook conventional health needs assessment, but experienced difficulty reviewing referral practice and controlling the volume of secondary care services, contributing to problems of financial control. Though TPP has been abolished, the findings have implications for successors.
We aimed to assess the acceptability of a variety of formulations of female-controlled methods of protection against HIV and STDs among men and women in south-western Uganda. Pilot interviews were carried out with 50 men and 55 women and 25 focus group discussions (FGDs) were held with 138 women and 42 men. The female condom, foaming tablets, sponge, foam, gel and film were demonstrated to 146 women and 35 of their male partners, who then tried out 2 of the products. They were interviewed 7 times during the course of 5 months. At the end experiences were evaluated during a second series of FGDs. Sixty-five (45%) women completed the trial. The main reasons for non-completion were related to geographical mobility. Product preference after the initial demonstration was similar to that at the end of the trial. The most popular formulations were the sponge (25% of the women), foaming tablets (23%), and the female condom (19%). The foam was of medium popularity (16%). The gel (9%) and film (7%) were least popular. Ten per cent of the women and 14% of the men reported products interfering with sexual enjoyment; 24% of the women and 67% of the men said products increased enjoyment. 'Dry sex' is not popular in this area and increased lubrication was an important determinant of acceptability. Age, level of education and location did have some effect on preference. Although secrecy was a dominant theme in the FGDs, 87% of the women had informed their partners by the end of the trial. The products were generally well received. Female control was an important issue for both sexes. Male attitudes were ambivalent because female ownership of products increased women's control. Although they have clear preferences, women appear to accept the products generally and might use a single available product just as readily if choice was limited, as long as it conforms to general cultural preferences, such as those relating to wet/dry sex.
This report describes a patient who experienced a generalized allergic reaction to Pergonal during controlled ovarian hyperstimulation in preparation for an intracytoplasmic sperm injection procedure for treatment of severe male factor infertility. The report describes a successful desensitization protocol which allowed the patient to complete her treatment cycle despite the allergic reaction to Pergonal. Subsequently recombinant follicle stimulating hormone was used successfully in inducing follicular growth in the absence of any allergic reactions. Therefore, this report confirms other studies which have suggested that an allergic reaction to human menopausal gonadotropins is due to impurities in such urine-derived products.