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Biomedical subjects

S Harrison

Publications and source records attributed to S Harrison.

At least 37 records · Page 2Linked to original sources
PubMed1997

Does short-term group therapy affect unexplained medical symptoms?

This paper describes an intensive time-limited group-therapy program conducted in a busy surgical clinic by two nursing staff with the support of a consultant psychiatrist. Nineteen patients with chronic idiopathic facial pain were recruited to the study and underwent weekly group therapy over 8 weeks. At the end of the study period, results showed decreases in pain, anxiety and depression scores, along with an improvement in the patients coping skills. The findings support the use of group psychological interventions undertaken by appropriately trained nursing staff in reducing symptoms associated with chronic idiopathic facial pain.

Adult↗
PubMed1997

The effect of okadaic acid on non-adrenergic non-cholinergic contraction in guinea-pig isolated bronchus.

1. We have investigated the role of phosphatases in modulating contractile responses to electrical field stimulation (EFS), methacholine, substance P and capsaicin in guinea-pig isolated main bronchus by use of the phosphatase 1 and 2A inhibitor okadaic acid. 2. Non-adrenergic non-cholinergic (eNANC) contractile responses were elicited by EFS (3 Hz, 20 s, 0.5 ms max. voltage) in the guinea-pig isolated main bronchus in the presence of the non-selective muscarinic antagonist, atropine (1 microM), the non-selective beta-adrenoceptor antagonist; propranolol (1 microM), the neutral endopeptidase inhibitor thiorphan (10 microM) and the cyclo-oxygenase inhibitor, indomethacin (5 microM). Okadaic acid significantly attenuated eNANC contractile responses (% inhibition) elicited by EFS (0.01 microM, 15.2 +/- 26.9%; 0.03 microM, 30.4 +/- 13.9%; 0.01 microM, 39.8 +/- 5.1%; 0.3 microM, 59.5 +/- 8.7%; 1 microM 77.8 +/- 7.8%; P < 0.05, n = 4). In contrast, the inactive analogue 1-Nor okadaone (0.3 microM) failed to attenuate significantly eNANC contractile responses (% inhibition elicited by 1-Nor okadaone, -1.25 +/- 8.5% vs dimethylsulphoxide (DMSO), -13.5 +/- 21.5%; P > 0.05, n = 4). 3. Cholinergic contractile responses were elicited by EFS (1-30 Hz, 10 s, 0.5 ms max. voltage) in guinea-pig isolated bronchus in the presence of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME, 30 microM). Okadaic acid failed to attenuate significantly the contractile (% methacholine Emax) response elicited by EFS at all frequencies tested compared with the control (1 Hz, control, 22 +/- 7.9% vs okadaic acid, 18 +/- 7.7%; 3 Hz, control, 26 +/- 6.9% vs okadaic acid, 27 +/- 9.1%; 10 Hz, control, 36 +/- 7.6% vs okadaic acid, 33 +/- 8.9%; 30 Hz, control, 50 +/- 7.6% vs okadaic acid, 42 +/- 14%; P > 0.05, n = 4). 4. Okadaic acid (0.3 microM) failed to alter significantly the contractile potency (pD2) to capsaicin (okadaic acid, 9.0 +/- 0.5, vs DMSO, 9.2 +/- 0.4; P > 0.05 n = 6), substance P (okadaic acid, 7.6 +/- 0.3 vs DMSO, 8.2 +/- 0.2; P > 0.05 n = 7) or methacholine (okadaic acid, 6.4 +/- 0.2 vs DMSO, 6.4 +/- 0.3; P > 0.05 n = 4). 5. Okadaic acid (0.01-1 microM) did not appear to reverse substance P-induced tone. The maximal relaxant response (% reversal of substance P-induced tone) mediated by okadaic acid (1 microM) was 33 +/- 11.7% (n = 4), this was not significantly different from the DMSO (0.8%) or a time-dependent fall in tone of 34.3 +/- 23.1% (n = 4) and 33 +/- 15.8% (n = 4), respectively. Okadaic acid (0.3 microM) failed to augment isoprenaline-induced relaxation responses in substance P contracted bronchus (okadaic acid, 6.5 +/- 0.4 vs DMSO, 5.9 +/- 0.3; P > 0.05, n = 9). 6. These results indicate that protein phosphatases appear to regulate the release of sensory neuropeptides from airway sensory nerves in response to electrical field stimulation.

Animals↗
PubMed1997

Immunologic responses to vaccinia vaccines administered by different parenteral routes.

To develop a less reactogenic but equally immunogenic vaccine, this study of 91 human volunteers compared the safety and immunogenic potency of a new, cell culture-derived vaccinia virus vaccine administered intradermally and intramuscularly with the licensed vaccinia vaccine administered by scarification. Cutaneous pox lesions developed in a higher proportion of scarification vaccinees. Scarification and intradermal vaccine recipients who developed cutaneous pox lesions had more local reactions but also achieved significantly higher cell-mediated and neutralizing antibody responses than those who did not develop pox lesions. Although less reactogenic, intradermal or intramuscular administration of vaccinia vaccine without the concomitant development of a cutaneous pox lesion induced lower immune responses.

Antibodies, Viral↗
PubMed1997

Glial development in the Drosophila CNS requires concomitant activation of glial and repression of neuronal differentiation genes.

Two classes of glial cells are found in the embryonic Drosophila CNS, midline glial cells and lateral glial cells. Midline glial development is triggered by EGF-receptor signalling, whereas lateral glial development is controlled by the gcm gene. Subsequent glial cell differentiation depends partly on the pointed gene. Here we describe a novel component required for all CNS glia development. The tramtrack gene encodes two zinc-finger proteins, one of which, ttkp69, is expressed in all non-neuronal CNS cells. We show that ttkp69 is downstream of gcm and can repress neuronal differentiation. Double mutant analysis and coexpression experiments indicate that glial cell differentiation may depend on a dual process, requiring the activation of glial differentiation by pointed and the concomitant repression of neuronal development by tramtrack.

Animals↗
PubMed1996

The indirect immunobead test for seminal antisperm antibodies and fertilization rates at in-vitro fertilization.

A series of 183 patients with positive indirect immunobead tests on semen was studied to determine the correlation in semen between specific antibody types, binding sites, antibody concentration, and fertilizing ability. IgM was present in only 44 ejaculates and was present in sufficient quantity to cause significant binding to immunobeads (i.e. >20% of motile donor spermatozoa) in only three of them. There was no correlation between the percentages of motile donor spermatozoa that bound IgA and IgG immunobeads but the two classes of beads generally bound to the same region of the spermatozoa. A total of 63 couples went on to attempt in-vitro fertilization (IVF) treatment, all with mature eggs recovered. Of these mature eggs, 44% were fertilized and cleaved normally in comparison to 68% in a group of patients with tubal disease. Fertilization rates in individuals followed a bimodal distribution with a substantial number of couples experiencing zero or very poor rates (0-20%), the mode for the remainder lying between 60 and 80%. The fertilization rate tended to decrease as the amount of antibody increased. The percentage of donor spermatozoa that bound to immunobeads, taken as the greater of IgA and IgG, was selected by logistic regression as a significant predictor of poor fertilization (rate <=25%). The predictive power of the equation was improved by including the motile normal sperm concentration but the equation could only account for a small proportion of the total variation in fertilization rate. The presence of antibodies to the sperm head was highly correlated with the antibody concentration but was not selected as a predictor of fertilization. We conclude that the nature of the antigen against which the seminal antisperm antibody is directed may be as important as the antibody concentration in affecting sperm function. There seems to be little practical value in measuring IgM in seminal plasma.

Adult↗
PubMed1996

End of the line? Tramtrack and cell fate determination in Drosophila.

Cell differentiation reflects the balance of two opposing influences, pathways which confer specialized properties on specific cells or groups of cells, and antagonising mechanisms which modulate responsiveness to such differentiative cues. It appears that the zinc finger protein Tramtrack (Ttk) fulfils the latter function in the CNS and PNS of Drosophila. Ttk seems to be able to inhibit neural development by down-regulating competence to respond to neuralising signals. We speculate, however, that restriction of neural competence is merely one example of a more general ability of Ttk to influence differentiation and that, given its widespread expression profile, Ttk might be implicated in a number of differentiative events.

Animals↗
PubMed1996

Health Management Guide. Disease management.

Disease management has been described as a comprehensive, integrated approach to care and reimbursement based on the natural course of a disease. It requires a management approach which brings together research evidence, best practice and inter-professional and inter-agency working. Starting with the ideal of continuity of care for individual patients, it implies structured co-ordination of care over time and across primary, secondary and tertiary settings. The appeal of disease management is that it promises reduced costs, combined with increased quality of care and patient satisfaction. But the concept is open to different definitions and interpretations and its effectiveness in improving UK healthcare is still largely untested. This Health Management Guide removes the mystique behind disease management and puts it in the context of existing knowledge and practice. Treating it as a concept, rather than a specific technique, it distinguishes between its different potential applications, offers practical guidance on implementation, and reports on how NHS organisations are taking it forward.

Asthma↗
PubMed1996

General practice fundholding in the UK National Health Service: evidence to date.

The published evidence on the effects of General Practitioner Fundholding, a major feature of the 1991 reorganization of the UK National Health Service, is reviewed with regard to the source and character of the evidence, as well as the findings on the outputs (including referrals, prescribing, service shifts, and the attitudes of various actors); the processes (inter- and intra-organizational); and the inputs (costs). An overall assessment based on this evidence is presented; the latest political and organisational developments in NHS primary care are outlined; and the future of GP fundholding is discussed.

Cost-Benefit Analysis↗
PubMed1995

The eastern Australian childhood nevus study: prevalence of atypical nevi, congenital nevus-like nevi, and other pigmented lesions.

BACKGROUND: Various melanocytic lesions are frequently observed. An understanding of phenotypic factors and environmental stimuli that are associated with these lesions may help explain their pathogenesis. OBJECTIVE: This study was undertaken to determine the prevalence of atypical nevi, blue nevi, cafe-au-lait macules, congenital nevus-like nevi, halo nevi, nevi spili, nevi 5 mm or more in diameter, and skin-colored melanocytic nevi in a population of schoolchildren and to explore risk factors including solar radiation in the development of these melanocytic lesions. METHODS: A cross-sectional study was performed by the same medical investigators to examine schoolchildren in three Australian cities that span a wide range of latitudes. RESULTS: Data from 1123 white Australian schoolchildren, 6 to 15 years of age, were analyzed. Acquired melanocytic nevi (atypical nevi, nevi > or = 5 mm in diameter, and skin-colored nevi) were more likely to develop in older fair-skinned subjects who had freckles and lived closest to the equator. Café-au-lait macules and congenital nevus-like nevi were observed in 36.3% and 4.4% of the total population, respectively. Prevalence for both these types of melanocytic lesions increased significantly with decreasing latitude. Halo nevi were present in 5.3% of the subjects and were usually solitary. These lesions were related to the presence of atypical nevi primarily by virtue of their size rather than of other features of clinical atypia. CONCLUSION: Like melanocytic nevi in general, large and atypical nevi are strongly influenced by geographic location and, by implication, degree of solar radiation. The same can be said for congenital nevus-like nevi, which suggests that many so-called congenital nevi are in fact acquired early in life.

Adolescent↗
PubMed1995

A cluster of cases of streptococcal necrotizing fasciitis in Gloucestershire.

We describe the first cluster of cases of necrotizing fasciitis (NF) in this century in the United Kingdom (UK). Between 1 January and 30 June 1994 there were six cases (five confirmed, one probable) of Streptococcus pyogenes NF in west Gloucestershire, population 320,000. Two cases died. The first two patients probably acquired their infections during the course of elective surgery performed in the same operating theatre, possibly from a nasopharyngeal carrier amongst the theatre staff. The remaining infections were community-acquired. Of 5 S. pyogenes isolates there were 2 M1 strains, 1 M3, 1 M5 and 1 M non-typeable strain. S. pyogenes NF had not been recorded in west Gloucestershire in the preceding 10 years and the incidence of S. pyogenes bacteraemia in England and Wales had not risen in the past 5 years. The two presumably theatre-acquired infections raised several issues. The need for detailed bacteriological investigation of all cases of post-surgical NF was confirmed. Clusters of S. pyogenes infection following surgery should be managed by closure of the operating theatre until all staff have been screened for carriage. Closure of an operating theatre and screening of staff following a sporadic case is probably not justified because of the infrequency of surgical cross-infection with S. pyogenes. Regular, routine screening of theatre staff is neither practical nor necessary.

Aged↗
PubMed1995

A policy agenda for health care rationing.

In any system of third party payment for health care, such care will be rationed. A clear policy agenda will be focused upon three questions: Who should ration? What mechanisms should exist for making and implementing rationing decisions? What are the criteria by which rationing should occur?

Decision Making↗
PubMed1995

Regulation by phosphodiesterase isoenzymes of non-adrenergic non-cholinergic contraction in guinea-pig isolated main bronchus.

1. We have investigated the role of phosphodiesterase isoenzymes in modulating electric field stimulation (EFS), substance P and capsaicin-induced contraction of the guinea-pig isolated main bronchus. 2. Non-adrenergic non-cholinergic contractile responses were elicited by EFS (3 Hz, 20 s) in the guinea-pig isolated main bronchus in the presence of the non-selective muscarinic antagonist, atropine (0.1 microM), the non-selective beta-adrenoceptor antagonist, propranolol (1 microM), the neutral endopeptidase inhibitor, thiorphan (10 microM) and the cyclo-oxygenase inhibitor, indomethacin (5 microM). The type III, type III/IV, type IV and type V phosphodiesterase isoenzyme inhibitor, SKF 94836, benzafentrine, Ro-20-1724 and zaprinast respectively, significantly attenuated the contractile response to EFS. The IC50 (95% confidence limits) value for SKF 94836, benzafentrine, Ro-20-1724 and zaprinast was 8.3 microM (0.89-78); 0.7 microM (0.1-4.5); 0.5 microM (0.2-1.2) and 13 microM (2-87) respectively. 3. The phosphodiesterase isoenzyme inhibitors, SKF 94836, Ro-20-1724 and zaprinast, partially attenuated the contractile response to substance P (10 nM). Benzafentrine significantly inhibited the contractile response to substance P, yielding an IC50 value of 1.9 microM (0.9-3.8). 4. The phosphodiesterase isoenzyme inhibitor, Ro-20-1724 (0.1-100 microM) failed to reduce significantly the contractile potency of capsaicin (P > 0.05). In contrast, SKF 94836 (1 microM), benzafentrine (10 microM) and zaprinast (100 microM) significantly reduced the contractile potency of capsaicin (P < 0.05). 5 The selective phosphodiesterase isoenzyme inhibitors, SKF 94836, benzafentrine, Ro-20-1724 andzaprinast (0.01-100 microM) reversed in a concentration-dependent manner the contractile response toexogenously administered capsaicin (EC50) yielding ICm values of 3.91 microM (0.68-22); 3.37 microM (1.86-6.11); 0.366 microM (0.201-0.564) and 50.1 microM (18.6- 135) respectively.6 In conclusion, phosphodiesterase isoenzymes appear to regulate the contractile response to electricalfield stimulation and our results provide circumstantial evidence for a regulatory role ofphosphodiesterase type IV isoenzyme on sensory nerve function in vitro.

Animals↗
PubMed1995

Early responses of trans-activating factors to growth hormone in preadipocytes: differential regulation of CCAAT enhancer-binding protein-beta (C/EBP beta) and C/EBP delta.

Using the 3T3-F442A preadipocyte line as a model of GH-dependent differentiation, early changes in the DNA-binding affinity of transcription factors in response to GH addition were investigated. Addition of 50 ng/ml human GH to cells in chemically defined medium led to a rapid increase in binding activity of activator protein 1 (AP-1) and CCAAT enhancer-binding protein (C/EBP), which was significant at 30 min and reached maximal induction by 2 h (3-fold for AP-1, 2.5-fold for C/EBP). Induction in AP-1 DNA binding correlates with a concomitant GH trans-activation of c-jun and c-fos genes described previously. Using specific antibodies in electrophoretic mobility shift assays and Western blots, it was shown that the increase in activity of C/EBP is the result of an increase in synthesis of two alternatively translated forms of C/EBP beta: 40-C/EBP beta and 23-C/EBP beta. This increase in protein was not accompanied by alteration in mRNA level and could be blocked by a Janus kinase 2 tyrosine kinase inhibitor and a C kinase inhibitor at concentrations shown to inhibit GH-dependent activation of microtubule-associated protein (MAP) kinases. Concomitant with the translationally activated increase in C/EBP beta, a GH-dependent increase was observed in C/EBP delta transcription. This was accompanied by an increase in mRNA for C/EBP delta, which was superinduced by cycloheximide and, unlike the increase in C/EBP beta protein, was not observed with insulin. Thus GH exerts its effects on C/EBP isoforms at two levels: transcriptional activation of C/EBP delta and translational activation of C/EBP beta. It is proposed that GH-dependent phosphorylation results in the efficient translation of 40-C/EBP beta and 23-C/EBP beta (the mouse homolog of the inhibitor liver-enriched inhibitory protein), and that together with the induction of C/EBP delta, these may be involved in initiating the adipocyte differentiation program.

3T3 Cells↗
PubMed1995

Localization of the response elements of a gene induced by intermittent growth hormone stimulation.

Three regions required for the expression of a mouse major urinary protein (MUP) transgene were identified by a deletion analysis. One of these was located upstream of the cap site between -2139 and -1800, another was the proximal promoter region downstream of -324 and the third lay within the 338 nucleotide intron 1. Both the proximal promoter and intron 1 are involved in sexually dimorphic expression of the transgene (male/female ratio 20), which is dictated by the different temporal profiles of circulating GH in the two sexes. The data also indicated that the region between exons 3 and 7 may contribute to full expression in males and that a region between -718 and -324 may contribute towards the low expression level that obtains in females, but compared with the three principal regions the effects of these regions are relatively minor. We propose (1) that full expression of the transgene requires the co-operation of transcription factors bindings to the three principal regions and (2) that the difference in expression between the sexes relates to interactions between transcription factors bound to the proximal promoter and to sites in intron 1. Our results complement earlier in vitro footprinting and gel-retardation studies of the homologous rat apha 2u-globulin genes. These identified a number of response elements, including putative C/EBP and AP1 sites in the proximal promoter and intron 1 respectively and three putative psi NF-1 sites, two in the proximal promoter and one in intron 1, but proof of the functionality of these sites in regulating transcription was lacking. The proximal promoter also contained a 34 nucleotide sequence that has 70% identity with the SPI GH response element.

Alpha-Globulins↗