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H Smith

Publications and source records attributed to H Smith.

At least 73 records · Page 4Linked to original sources

In a medium containing glucose, lactate carbon is incorporated by gonococci predominantly into fatty acids and glucose carbon incorporation is increased: implications regarding lactate stimulation of metabolism.

The reason for stimulation by lactate of metabolism of gonococci growing in a medium containing glucose, which enhances pathogenicity by increasing growth rate, lipopolysaccharide (LPS) synthesis and protein formation, has been investigated. Tricine dodecylpolyacrylamide gel electrophoresis (SDS-PAGE) and thin layer chromatography (TLC) on homogenates of gonococci grown in this medium with [14C]lactate showed that lactate carbon was preferentially incorporated into lipid and LPS. Nuclear magnetic resonance (NMR) spectroscopy on lipid extracted from gonococci grown in the glucose containing medium with [13C]lactate showed that lactate carbon was incorporated into fatty acid moieties and not into ethanolamine or glycerol moieties. In contrast, NMR on lipid from gonococci grown with [13C]glucose indicated glucose carbon in both moieties. When unlabelled lactate was added, lipid synthesis from [l3C]glucose was stimulated and small amounts of different fatty acids were formed. The NMR data shows that gluconeogenesis from lactate carbon does not occur in the presence of glucose, suggesting that lactate is used solely for rapid production, via pyruvate, of acetyl CoA, the precursor not only for fatty acid synthesis but also for the constituents and products of the citric acid cycle, including ATP. The rapid formation of a high level of acetyl CoA is the probable reason for the stimulation of metabolism and oxygen uptake by lactate. 14C label on LPS was detected in its fatty acids. Most proteins that stained with silver in tricine SDS-PAGE were not significantly labelled by [14C]lactate in the glucose-containing medium. Two of three appreciably labelled proteins were identified by N-terminal sequencing as GroEL and porin 1B, and one of the two less labelled proteins was similar to peroxiredoxin type proteins. There were no signs of specific induction of these proteins by lactate and their labelling was consistent with fatty acids in attached lipid.

Bacterial Proteins↗

Host factors that influence the behaviour of bacterial pathogens in vivo.

Interest is increasing in how bacteria behave and produce virulence determinants within the infected host. There are three aspects of this process; observations on the bacteria themselves, recognition of host factors that affect them and investigation of metabolic interactions between the two. The first aspect is relatively easy to investigate and attracts much interest. The second and third are difficult to work on and hence understudied. The review aims to stimulate interest in them by indicating methods of investigation and describing some successful studies. After discussing host factors that determine growth in vivo consideration is given to factors that influence the production of the determinants of mucosal colonization, penetration, interference with host defence and damage to the host. The final section deals with the influence of host-derived cytidine 5'-monophospho-N-acetyl neuraminic acid and lactate on the pathogenicity of gonococci, meningococci and Haemophilus influenzae.

Cytidine Monophosphate N-Acetylneuraminic Acid↗

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Journal Article↗

Groin hernia repair in Scotland.

BACKGROUND: The use of mesh for groin hernia repair has dramatically changed the way this common operation is performed. The aim of this study was to survey the methods of groin hernia repair in Scotland and to assess patient satisfaction with the operation. METHODS: Between 1 April 1998 and 31 March 1999 all patients who underwent groin hernia repair in the National Health Service in Scotland were identified. As well as looking at the type of hernia repair performed and postoperative morbidity, patients were sent a Short Form-36 about 3 months after the operation to assess satisfaction and return to normal activity. RESULTS: Information was obtained on 5506 (97 per cent) of patients who underwent groin hernia repair during the study period. Eighty-five per cent of patients had an open mesh repair and 4 per cent had a laparoscopic repair. Most operations (85 per cent) were performed using general anaesthesia on an inpatient basis (78 per cent), and 8 per cent were for repair of a recurrent hernia. Potentially serious intraoperative complications were rare (seven patients), although they were significantly (P < 0. 001) more likely to be associated with a laparoscopic approach or repair of a femoral hernia: relative risk compared with open inguinal hernia repair 33 (95 per cent confidence interval (c.i.) 6-197) and 22 (95 per cent c.i. 3-152) respectively. Wound complications were common and 10 per cent of patients required a district nurse to attend the wound. Patients expressed a high degree of satisfaction; 94 per cent would recommend the same operation to someone else if required. CONCLUSION: An open mesh repair using general anaesthesia has become the repair of choice for a groin hernia in Scotland. Despite a high incidence of wound complications, patients are satisfied with this operation.

Aged↗

Identification of transcription activators that regulate gonococcal adaptation from aerobic to anaerobic or oxygen-limited growth.

Analysis of the Neisseria gonorrhoeae DNA sequence database revealed the presence of two genes, one encoding a protein predicted to be 37. 5% identical (50% similar) in amino acid sequence to the Escherichia coli FNR protein and the other encoding a protein 41% and 42% identical (54 and 51% sequence similarity) to the E. coli NarL and NarP proteins respectively. Both genes have been cloned into E. coli and insertionally inactivated in vitro. The mutated genes have been transformed into gonococci and recombined into the chromosome. The fnr mutation totally abolished and the narP mutation severely diminished the ability of gonococci to: (i) grow anaerobically; (ii) adapt to oxygen-limited growth; (iii) initiate transcription from the aniA promoter (which directs the expression of a copper-containing nitrite reductase, AniA, in response to the presence of nitrite); and (iv) reduce nitrite during growth in oxygen-limited media. The product of nitrite reduction was identified to be nitrous oxide. Immediately upstream of the narL/narP gene is an open reading frame that, if translated, would encode a homologue of the E. coli nitrate- and nitrite-sensing proteins NarX and NarQ. As transcription from the aniA promoter was not activated during oxygen-limited growth in the presence of nitrate, the gonococcal two-component regulatory system is designated NarQ-NarP rather than NarX-NarL. As far as we are aware, this is the first well-documented example of a two-component regulatory system working in partnership with a transcription activator in pathogenic neisseria. A 45 kDa c-type cytochrome that was synthesized during oxygen-limited, but not during oxygen sufficient, growth was identified as a homologue of cytochrome c peroxidases (CCP) of other bacteria. The gene for this cytochrome, designated ccp, was located, and its regulatory region was cloned into the promoter probe vector pLES94. Transcription from the ccp promoter was repressed during aerobic growth and induced during oxygen-limited growth and was totally FNR dependent, suggesting that the gonococcal FNR protein is a transcription activator of at least two genes. However, unlike AniA, synthesis of the CCP homologue was insensitive to the presence of nitrite during oxygen-limited growth.

Adaptation, Physiological↗

Physiological interactions of phytochromes A, B1 and B2 in the control of development in tomato.

The role of phytochrome B2 (phyB2) in the control of photomorphogenesis in tomato (Solanum lycopersicum L.) has been investigated using recently isolated mutants carrying lesions in the PHYB2 gene. The physiological interactions of phytochrome A (phyA), phytochrome B1 (phyB1) and phyB2 have also been explored, using an isogenic series of all possible mutant combinations and several different phenotypic characteristics. The loss of phyB2 had a negligible effect on the development of white-light-grown wild-type or phyA-deficient plants, but substantially enhanced the elongated pale phenotype of the phyB1 mutant. This redundancy was also seen in the control of de-etiolation under continuous red light (R), where the loss of phyB2 had no detectable effect in the presence of phyB1. Under continuous R, phyA action was largely independent of phyB1 and phyB2 in terms of the control of hypocotyl elongation, but antagonized the effects of phyB1 in the control of anthocyanin synthesis, indicating that photoreceptors may interact differently to control different traits. Irradiance response curves for anthocyanin synthesis revealed that phyB1 and phyB2 together mediate all the detectable response to high-irradiance R, and, surprisingly, that the phyA-dependent low-irradiance component is also strongly reduced in the phyB1 phyB2 double mutant. This is not associated with a reduction in phyA protein content or responsiveness to continuous far-red light (FR), suggesting that phyB1 and phyB2 specifically influence phyA activity under low-irradiance R. Finally, the phyA phyB1 phyB2 triple mutant showed strong residual responsiveness to supplementary daytime FR, indicating that at least one of the two remaining phytochromes plays a significant role in tomato photomorphogenesis.

Base Sequence↗

Head-shaking nystagmus (HSN): the theoretical explanation and the experimental proof.

Head-shaking nystagmus (HSN) is induced by oscillating the head at high frequency in the horizontal plane. This test is used in the clinic to detect the presence of a unilateral loss of vestibular function. HSN has been described as monophasic with fast-phase direction towards either side, or biphasic with the direction of fast phases reversing after a few seconds. Loss of vestibular function amplifies existing non-linearities in the vestibular system, so that imposed sinusoids can induce biases which are the source of HSN. Fifty-one patients suffering from loss of peripheral vestibular function (43 partial, 11 total unilateral tests) were exposed to whole-body sinusoidal stimulation, with increasing head velocities (90-220 degrees/s) at 1/6Hz, to explore the consistency of per-rotatory induced biases. A bias was induced in all cases, but it wandered on either side, healthy or pathologic, unless test head velocities were larger than approximately 180 degrees/s. Given this condition, the slow-phase bias was located towards the pathologic side for all patients with significant bias ( > 5 degrees/s). These observations demonstrate that the sign and amplitude of the bias is variable and is not correlated with the lesioned side, unless high head velocities are imposed. This explains why the direction of the initial phase of HSN in the clinic seems so labile. Subsequent monophasic or biphasic characteristics of HSN are simply the reflection of interactions between two main time constants associated with "velocity storage" and "gaze holding" in the vestibular central processes.

Adult↗

Expanding epidemiology of blastomycosis: clinical features and investigation of 2 cases in Colorado.

On the basis of case reports of blastomycosis, Blastomyces dermatitidis is widely accepted to be endemic in the central United States in and around the Ohio and Mississippi River Valleys. Blastomycosis also occurs in parts of Canada and in the southeastern United States. However, there has been no large-scale skin testing, and the environmental range of B. dermatitidis may have been underestimated. We describe 2 immunocompetent patients with blastomycosis acquired while working in the Front Range region of the Rocky Mountains. The patients were coworkers engaged in a prairie dog relocation project. In the course of this work, they had extensive contact with contaminated soil. Significantly above-average rainfall before the exposure may have contributed to favorable conditions for sporulation of the fungus.

Adult↗

Clinical governance in primary care groups: the feasibility of deriving evidence-based performance indicators.

OBJECTIVES: To test the feasibility of deriving comparative indicators in all the practices within a primary care group. DESIGN: A retrospective audit using practice computer systems and random note review. SETTING: A primary care group in southern England. SUBJECTS: All 18 general practices in a primary care group. MAIN OUTCOME MEASURES: Twenty six evidence-based process indicators including aspirin therapy in high risk patients, detection and control of hypertension, smoking cessation advice, treatment of heart failure, raised cholesterol levels in those with established cardiovascular disease, and the treatment of atrial fibrillation. Feasibility was tested by examining whether it was possible to derive these indicators in all the practices; the problems and constraints incurred when collecting data; the variations in indicator values between practices in both their identification of diseases and in the uptake of various interventions; the possible reasons for these variations; and the cost of generating such indicators. RESULTS: It was possible to derive eight indicators in all practices and in three practices all 26 indicators. The median number of indicators derived was 12 with two practices able to generate eight. There was considerable variation in the use of computers between practices and in the ability and ease of various practice computer systems to generate indicators. Practices varied greatly in the identification of diseases and in the uptake of effective interventions. Variation in identification of ischaemic heart disease could not be explained by a higher prevalence in practices with a more deprived population. The cost of generating these indicators was 5300 Pounds. CONCLUSION: Comparative evidence-based indicators, used as part of clinical governance in primary care groups, could have the potential to turn evidence into everyday practice, to improve the quality of patient care, and to have an impact on the population's health. However, to derive such indicators and to be able to make meaningful comparisons primary care groups need greater conformity and compatibility of computer systems, improved computer skills for practice staff, and appropriate funding.

Benchmarking↗

Reactions to the use of evidence-based performance indicators in primary care: a qualitative study.

OBJECTIVES: To investigate reactions to the use of evidence-based cardiovascular and stroke performance indicators within one primary care group. DESIGN: Qualitative analysis of semi-structured interviews. SETTING: Fifteen practices from a primary care group in southern England. PARTICIPANTS: Fifty two primary health care professionals including 29 general practitioners, 11 practice managers, and 12 practice nurses. MAIN OUTCOME MEASURES: Participants' perceptions towards and actions made in response to these indicators. The barriers and facilitators in using these indicators to change practice. RESULTS: Barriers to the use of the indicators were their data quality and their technical specifications, including definitions of diseases such as heart failure and the threshold for interventions such as blood pressure control. Nevertheless, the indicators were sufficiently credible to prompt most of those in primary care teams to reflect on some aspect of their performance. The most common response was to improve data quality through increased or improved accuracy of recording. There was a lack of a coordinated team approach to decision making. Primary care teams placed little importance on the potential for performance indicators to identify and address inequalities in services between practices. The most common barrier to change was a lack of time and resources to act upon indicators. CONCLUSION: For the effective implementation of national performance indicators there are many barriers to overcome at individual, practice, and primary care group levels. Additional training and resources are required for improvements in data quality and collection, further education of all members of primary care teams, and measures to foster organisational development within practices. Unless these barriers are addressed, performance indicators could initially increase apparent variation between practices.

Adult↗

Effects of forearm bier block with bretylium on the hemodynamic and metabolic responses to handgrip.

We tested the hypothesis that a reduction in sympathetic tone to exercising forearm muscle would increase blood flow, reduce muscle acidosis, and attenuate reflex responses. Subjects performed a progressive, four-stage rhythmic handgrip protocol before and after forearm bier block with bretylium as forearm blood flow (Doppler) and metabolic (venous effluent metabolite concentration and (31)P-NMR indexes) and autonomic reflex responses (heart rate, blood pressure, and sympathetic nerve traffic) were measured. Bretylium inhibits the release of norepinephrine at the neurovascular junction. Bier block increased blood flow as well as oxygen consumption in the exercising forearm (P < 0.03 and P < 0.02, respectively). However, despite this increase in flow, venous K(+) release and H(+) release were both increased during exercise (P < 0.002 for both indexes). Additionally, minimal muscle pH measured during the first minute of recovery with NMR was lower after bier block (6.41 +/- 0.08 vs. 6.20 +/- 0.06; P < 0.036, simple effects). Meanwhile, reflex effects were unaffected by the bretylium bier block. The results support the conclusion that sympathetic stimulation to muscle during exercise not only limits muscle blood flow but also appears to limit anaerobiosis and H(+) release, presumably through a preferential recruitment of oxidative fibers.

Adult↗

Dying at home: evaluation of a hospice rapid-response service.

Various studies suggest that there is a preference among patients, professionals and the public for death to occur at home (Dunlop et al, 1989; Townsend et al, 1990; Hinton, 1994). Data indicates that some patients are denied the opportunity to exercise choice in the place of death. In areas where palliative rapid-response teams have been available more people have been able to die at home. This article presents the findings of an evaluation of a hospice rapid-response service in the Highlands of Scotland, which was designed to respond to the needs of people in crisis facing death. The study was designed to produce a rigorous and comprehensive description of a newly-operational service at the pilot stage. It reflects not only the views of the professionals involved but also focuses on the views of informal carers. Seventeen patients were referred to the rapid-response service in its first year of operation between April 1998 and March 1999. The service has shown some success in enabling patients to die at home and satisfaction with the service is high among professionals and lay carers.

Community Health Nursing↗

An outbreak of multi-resistant Shigella sonnei in a long-stay geriatric nursing centre.

An outbreak of Shigella sonnei infection in a long-stay nursing centre was detected during routine surveillance of notifications in July 1999. Subsequent investigations identified 13 cases of multi-resistant S. sonnei infection affecting nine staff, three community members associated with the centre and one resident of the centre. Each isolate of S. sonnei was genetically indistinguishable. The outbreak investigation identified contact with residents with vomiting and diarrhoea as a significant risk factor for infection amongst staff providing nursing care. This association, and the duration of the outbreak over several months, suggests that transmission was most likely person-to-person. This outbreak demonstrates the importance of infection control policies and hygiene measures in long-stay nursing facilities.

Aged↗

Implementation of influenza immunisation policy in general practice: 1997 to 1998.

Influenza immunisation policy and practice in primary care in central southern England was surveyed in early 1998, when national guidelines advised immunisation only for people with specified 'higher risk' medical conditions or who lived in long stay facilities such as nursing or residential homes. Three hundred and one questionnaires were returned from 441 general practices (68%). Between 71% and 82% of all respondents stated that they 'always' offered influenza immunisation to adults with the specified 'higher risk' medical conditions. For children the corresponding range was 33% to 43%. We estimated that 11.5% of the combined practice population of two million had received influenza immunisation late in 1997. The age data supplied suggested that 64% of those aged over 75 years had been immunised. Seventy-four per cent of respondents said they would be willing to follow an age based policy. The total coverage figures mask suboptimal uptake in target groups, coupled with immunisation of those outside the target groups. This could be partly addressed by rewarding high coverage of target groups such as elderly people aged over 75 years and by clarifying the guidelines for immunisation of children with 'higher risk' medical conditions.

Adult↗

Family practice research networks. Experiences from 3 countries.

Access to data about the clinical problems, patients, and processes that characterise family practice is essential for the development of this specialty. Practice-based research networks (PBRNs) play an increasing role in obtaining these data. We compared 3 PBRNs: one in Wisconsin in the United States, one in Wessex in the United Kingdom, and one in Nijmegen in the Netherlands. We organized our data into 4 key areas for review: the mission of the network, its contribution to the evidence base of family medicine, the management of the network, and the financing of the network infrastructure. Extending the evidence base of family practice is the overriding objective of these networks, and their main focus is on common morbidities. They provide access to unselected patient populations, but there are differences in their size. There are aspects of PBRNs that are common in countries with different health care systems, despite the fact that local circumstances--the research mission or the characteristics of the health care system under which they operate--determine their form and structure. Networks develop over time and their focus and activities may evolve. Financial support for these networks continues to be a problem.

Family Practice↗