Biomedical subjects
Publications and source records attributed to S Harrison.
People who work in the control of communicable diseases often claim that incidents such as disease outbreaks tend to happen on Friday afternoons. A survey of outbreaks of foodborne illness did not support this belief, which we suggest is a myth.
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Much attention has focused on the important role played by phosphatases in the control of gene transcription, cell differentiation and memory regulation. It is also clear that phosphatases may regulate a number of biochemical pathways which can modulate cellular function. Of particular interest is the role of phosphatases in the control of neuronal function. Alterations in neuronal function may contributed to the heightened airways responsiveness observed in asthma to a number of physiological stimuli including distilled water, sulfur dioxide, metabisulfite, hypertonic saline, exercise, allergens, viruses and cold air. An understanding of the mechanisms which regulate the function of sensory nerves could have important clinical implications. In this review we will highlight a number of studies that have investigated the role of phosphatases in the regulation of airway nerve function.
The consistent and correct use of the male condom makes it highly effective in both disease prevention and as a contraceptive method. However, it is also well recognized that its use is under men's control. Because of this vital limitation, there have been frequent calls for female-controlled methods of HIV prevention, particularly from women from sub-Saharan Africa. Here we report on data collected in focus-group discussions (FGDs) with women aged 17-54 in South-Western Uganda. A total of 138 women, from rural villages, urban family planning clinics and a truck-stop town, were recruited to participate in 18 FGDs on the male condom, the female condom and existing formulations of vaginal microbicidal products. Three themes emerged: (i) problems with men's control over the male condom, (ii) the importance of control over and secrecy about protective measures and (iii) sexual pleasure associated with different methods. We found that the female condom, while being perceived as an improvement over the male condom, was recognized as having limited value because of the need to agree its use prior to sex taking place. Other products were considered to be significantly better than the female condom; the sponge, in particular, was perceived as having advantages over every other product. Women like the fact that it could be inserted some time before, and left in place some time after, sexual intercourse, that it was effective for multiple instances of intercourse, and that men would be unaware that it was being employed. Female-controlled methods to prevent sexually transmitted infections, including HIV, and to increase reproductive choice, hold the promise of ceding some control over sexual and reproductive health to women.
As part of a large IEC (Information, Education and Communication)/STD intervention trial, a 19-lesson, comprehensive school-based AIDS education programme was implemented and evaluated in 50 primary and 16 secondary schools in 12 parishes of Masaka District, Uganda. A series of three teacher-training and evaluation workshops spread over a year was held in each parish, between which teachers implemented the programme in the classroom. One hundred and forty-eight teachers were trained and about 3,500 students were subsequently exposed to the programme. Both teachers and students responded positively, which suggests that this type of programme has much to offer young people who attend school. However, some problems were encountered: language, programme content, community resistance to teaching about condoms, and several practical issues. Proposed solutions include flexibility with the English language policy, alternative approaches to role play activities, targeting influential individuals with information about the need for young people to learn about safer sex, and a parallel community-based IEC programme to facilitate community acceptance of the need for the programme. In addition, implementation may be incomplete unless comprehensive AIDS education is fully incorporated into the curriculum, and properly examined. These findings are placed in the context of other life skills/AIDS education programmes being introduced both in Uganda and elsewhere in Africa.
Total purchasing in primary care (TPPC) was piloted in the mid-1990's, first by four "pioneer sites", and later by over 80 first and second waves of "pilot sites". Separate evaluations of three of the pioneers show that they faced challenges similar to those experienced by the pilot sites, namely: the need to develop organisations which were effective both internally and, in their relationships with other health-care agencies, externally; and the difficulties encountered when attempting to change the behaviour of local acute care providers. Although GP fund holding and/or TPPC have had some successes in influencing the pattern of delivery for some elective and community services, the challenge of reducing hospital admissions and lengths of stay remains formidable.
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OBJECTIVE: To evaluate the use of magnetic resonance imaging (MRI) in making clinical decisions when assessing nonhealing pressure ulcers and nonhealing myocutaneous flaps for the presence of an abscess, osteomyelitis, sinus tracts, and fluid collections. DESIGN: Retrospective review of patient charts and radiographic studies. SETTING: Regional spinal cord injury center. SUBJECTS: Twelve patients who had MRI as part of their evaluation for a nonhealing pressure ulcer or myocutaneous flap. RESULTS: Seven patients had MRI for preoperative evaluation, four with a previous flap that had recurrent breakdown and three with a new grade III or IV ulcer. Five patients had MRI for postoperative evaluation of myocutaneous flaps with delayed healing. MRI was useful in identifying osteomyelitis in three patients and sinus tracts that required surgical revision in six patients. MRI was also used in two patients to assess the size of fluid collections postoperatively in determining whether the patients should be mobilized after surgery. These chronic nonhealing wounds resulted in multiple admissions and lengthy hospital stays and required multiple surgical revisions. Patients who did poorly with healing or had repeated breakdown tended to have concurrent issues such as poor self care, increased age, increased time of spinal cord injury, poor nutrition, or other medical problems. CONCLUSION: Chronic nonhealing pressure ulcers and myocutaneous flaps can be difficult to treat and evaluate with conventional methods. There are multiple reasons for failure to heal. MRI can be a useful tool for identifying some of these factors including osteomyelitis, fluid collections, abcesses, and sinus tracts in the perioperative period. Identifying the appropriate patient populations and clinical indications for the optimal use of MRI should be subject of further study.
Several clinical studies document a greater discrimination between asthmatic and healthy subjects in bronchial responsiveness to a range of stimuli such as cold air, distilled water and sodium metabisulphite, than to conventional bronchoconstrictor agonists including histamine and methacholine. One of the mechanisms thought to account for the bronchoconstriction induced by these agents is via reflex activation of the cholinergic pathway. An increase in sensory nerve (afferent) activity in asthma might account for the increased responsiveness to these agents. If so, a number of strategies are available to inhibit the function of afferent nerves which could lead to a suppression of bronchial hyperresponsiveness, including (1) inhibition of afferent activity, (2) inhibition of neuropeptide release and (3) antagonism of tachykinin receptors. As there are numerous reviews dealing with the latter, in this review Domenico Spina, Saloni Shah and Selena Harrison focus on the first two strategies.
With the use of tissue-expansion techniques, it is possible to elongate the facial nerve without impairing its function. The rate of expansion is limited by ischemic events imposed by stretching of the nerve and by anatomic characteristics of the nerve segment. In this study, we used various electroneurography techniques to determine the first sign of facial dysfunction during expansion. The main objective of the study was to ascertain test-retest variability of electroneurography techniques. Facial nerves were expanded in 16 cats with the use of a tissue expander secured more deeply to the main trunk. We conducted electroneurography measurements with the use of surface electrodes, temporary needle electrodes, and permanently implanted electrodes. Technique-dependent variations encountered with the surface electrodes made this method unreliable. Using implanted electrodes, we noted gradual worsening of the compound-action potential amplitude with increasing expansion. During acute expansion, reduction in compound-action potential amplitude was correlated with clinically observed deterioration of facial-nerve function. In this study, electroneurography with implanted electrodes was found to be the most reliable predictor of the rate of successful facial nerve expansion.
BACKGROUND: Strabismus can occur in as many as 30% of patients after scleral buckle procedures for retinal detachments. Most previous case series have reported on horizontal and vertical deviations. This study examines the frequency of torsion after scleral buckle procedures, the abnormalities of extraocular muscles seen during strabismus surgery, and the surgical procedures effective in improving torsion. METHODS: A chart review examined the records of all patients coming to a strabismus referral practice with diplopia reported > or =6 months after scleral buckle procedures. RESULTS: Forty-six percent of patients with diplopia after scleral buckle operations had torsion (88% extorsion, 12% intorsion). The 2 mechanisms that caused extorsion most frequently were inadvertent production of a superior oblique muscle palsy and tightening of the inferior rectus muscle from the underlying scleral buckle. Other mechanisms of extorsion were also seen. The mechanism for production of intorsion was scarring of the superior oblique muscle to the nasal border of the insertion of the superior rectus muscle. Surgical procedures were successful in reducing torsion 4 degrees or more in 59% of cases. CONCLUSION: In patients undergoing surgery for torsion after a scleral buckle procedure, exploration of the superior oblique muscle and the inferior rectus muscle may yield information about the mechanism involved in the production of the torsion.
We have investigated the contractile property of cyclosporin A and FK506 in guinea-pig isolated bronchus. Cyclosporin A (10 microM) failed to significantly attenuate the excitatory non-adrenergic non-cholinergic (eNANC) and cholinergic contractile response (per cent methacholine Emax) induced by electrical field stimulation (EFS). In contrast, eNANC responses were significantly attenuated by both the neurokinin (NK)-1 and (NK)-2 receptor antagonists, N-acetyl-L-tryptophan 3,5-bis (trifluoromethyl)-benzyl and SR48968, respectively. Cyclosporin A and FK506 caused a concentration-dependent contraction in guinea-pig isolated bronchus, which was significantly attenuated by NK-1 and NK-2 receptor antagonists. The capsaicin receptor antagonist, capsazepine (10 microM) significantly reduced the contractile response to cyclosporin A and capsaicin, but not to FK506. The N-type calcium channel blocker, omega-Conotoxin (omegaCTX: 10 nM), significantly reduced the contractile response to FK506 and the eNANC response following EFS. In contrast, omega-CTX failed to significantly reduce the contractile potency to capsaicin or cyclosporin A. In bronchial preparations desensitized by repeated application of capsaicin (1 microM), the contractile responses to both cyclosporin A (100 microM) and FK506 (100 microM), were significantly reduced. In contrast, the contractile responses to substance P and neurokinin A (10 microM) were not altered. Furthermore, repeated application of cyclosporin A (100 microM) significantly inhibited the contractile response to capsaicin (1 microM). The findings from this study would indicate that cyclosporin A and FK506 mediate contraction of guinea-pig isolated bronchus secondary to the release of neuropeptides from airway sensory nerves. However, the release of sensory neuropeptides appears to be mediated via different mechanisms for cyclosporin A and FK506, the former by stimulation of the vanilloid receptor and the latter via opening of N-type calcium channels.
Tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of catecholamine neurotransmitters, is expressed in a restricted number of areas, and subject to numerous regulations during development and in adulthood. Two transcription factor binding sites present in the proximal region of the TH gene, the TPA-responsive element (TRE) and the c-AMP responsive element (CRE), have been shown to play important roles in TH gene regulation in vitro. In order to elucidate in vivo the role of these two sites, we produced transgenic mice bearing a 5.3-kb fragment from the 5' flanking sequence of the TH gene with mutations in either the CRE-or TRE-sites. Using the intact 5.3-kb fragment fused to two different reporter genes (HSV1-tk and lacZ), we show that this promoter fragment is able to specifically direct expression in catecholaminergic tissues both in adult mice and embryos. Interestingly, the CRE- and TRE-mutated transgenes were not expressed in adult mice, contrary to the situation in embryos where they were specifically expressed in catecholaminergic regions. These results demonstrate that the CRE and TRE play an essential role in basal TH expression in adult tissues in vivo. Moreover, they suggest that distinct transcription factors are involved in TH regulation in developing and adult tissues. In support of this, gel mobility shift experiments revealed a complex present only in embryonic tissues. Taken together, these data highlight the diversity of the mechanisms underlying the establishment and maintenance of the catecholaminergic phenotype.
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PURPOSE: We studied whether the spermatozoa from sperm autoimmune infertile men undergo premature acrosomal loss and whether this relates to the presence of sperm antibodies in wives. MATERIALS AND METHODS: We evaluated acrosome status of live washed native and overnight capacitated spermatozoa from 17 sperm nonautoimmune fertile and 23 sperm autoimmune infertile men using an immunofluorescent peanut lectin binding assay. We used cytotoxic and immunobead binding assays to prescreen the serum and seminal plasma of these men, and serum and cervical mucus of the wives for immunological infertility. We performed immunofluorescent sperm antibody assays on all study samples to ascertain sperm antibody isotype levels in each sample. Levels of acrosomal loss in husband native and capacitated spermatozoa were correlated with levels of IgG, IgA and IgM sperm antibodies in the study samples. RESULTS: Sperm autoimmune infertile men had a significantly larger percentage of sperm (p <0.0001) that had lost the acrosome and a lower percentage of sperm with intact acrosome (p <0.0001) in native and capacitated preparations in contrast to those of fertile controls. Levels of cytotoxic and IgA antibodies, especially in seminal plasma and cervical mucus, correlated significantly with percentages of sperm with a total loss of acrosome in native and capacitated sperm preparations (p < or = 0.01). CONCLUSION: Infertile men with sperm antibodies in serum and seminal plasma undergo premature acrosome loss. This loss may expose the reproductive tract immune system, especially that involving IgA, in autoimmune infertile men and the wives to high immunogenic levels of sperm acrosome membrane antigens, thereby rendering them immunologically infertile.
We have investigated the effects of L-arginine, D-arginine and L-lysine on airway smooth muscle responsiveness to spasmogens in vitro. Both L-arginine and D-arginine (100 mM) significantly reduced the contractile potency and maximal contractile response to histamine but not to methacholine or potassium chloride in guinea-pig epithelium-denuded isolated trachea. Similarly, the contractile response to histamine was significantly reduced by L-arginine (100 mM) in rabbit epithelium-denuded isolated bronchus. The amino acid L-lysine (100 mM) failed to significantly alter the contractile potency of histamine in guinea-pig isolated trachea (P > 0.05). In guinea-pig isolated trachea precontracted with histamine, both L-arginine and D-arginine produced a concentration-dependent relaxation which was not significantly altered by epithelium removal or by the presence of the nitric oxide synthase inhibitor, NG-nitro L-arginine methyl ester (L-NAME; 50 microM). Thus, at very high concentrations, arginine exhibit a non-competitive antagonism of histamine-induced contraction of isolated airway preparations that was independent of the generation of nitric oxide and was not dependent on charge. These observations confirm previous studies of cutaneous permeability responses and of contractile responses of guinea-pig isolated ileal smooth muscle. Taken together, the data suggest that high concentrations of arginine can exert an anti-histamine effect.