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Biomedical subjects

J Clarkson

Publications and source records attributed to J Clarkson.

At least 19 recordsLinked to original sources
PubMed2006

Mitochondrial involvement in transhemispheric diaschisis following hypoxia-ischemia: Clomethiazole-mediated amelioration.

Mitochondria play a central role in both the physiological and pathophysiological regulation of cell survival/death. Increasing evidence places mitochondrial dysfunction at the center of many neuropathological conditions. The present study investigates the extent of mitochondrial dysfunction in cortical, hippocampal and cerebellar tissues in a rat model of hypoxia-ischemia (HI). We hypothesized that; mitochondrial dysfunction in situ may be prevented by treatment with clomethiazole (CMZ), a GABA(A) receptor agonist. Assessment of mitochondrial FAD-linked respiration at both 1- and 3-day post-HI revealed a marked decrease in activity from ipsilateral cortical and hippocampal regions (P<0.001). In addition, small changes were seen in contralateral cortical and hippocampal tissues as well as in the cerebellum at 3-days (P<0.05). Assessment of the mitochondrial electron transport chain (complexes I-V), and mitochondrial markers of integrity (citrate synthase) and oxidative stress (aconitase) confirmed mitochondrial impairment in ipsilateral regions following HI. Complexes I, II-III, V and citrate synthase were also impaired in contralateral regions and cerebellum 3-days post-HI. Treatment with CMZ (414 mg/kg/day via minipumps) provided marked protection to all aspects of neuronal tissue assessed. Circulating cytokine (interleukin [IL]-1alpha, IL-1beta, tumor necrosis factor [TNF]-alpha, granulocyte macrophage colony-stimulating factor [GM-CSF], IL-4 and IL-10) levels were also assessed in these animals 3-days post-HI. Plasma IL-1alpha, IL-1beta, TNF-alpha and GM-CSF levels were significantly increased post-HI. Treatment with CMZ ameliorated the increases in IL-1alpha, IL-1beta, TNF-alpha and GM-CSF levels while increasing plasma IL-4 and IL-10 levels. This study provides evidence of the extent of mitochondrial damage following an HI-insult. In addition, we have shown that protection afforded by CMZ extends to preservation of mitochondrial function and integrity via anti-inflammatory mediated pathways.

Animals↗
PubMed2006

Complete or ultraconservative removal of decayed tissue in unfilled teeth.

BACKGROUND: The treatment of deep dental decay has traditionally involved removal of all the soft demineralised dentine before a filling is placed. However this has been challenged in three groups of studies which involve sealing soft caries into the tooth. The three main groups either remove no caries and seal the decay into the tooth, remove minimal (ultraconservative) caries at the entrance to a cavity and seal the remaining caries in, or remove caries in stages over two visits some months apart to allow the pulp time to lay down reparative dentine (the stepwise excavation technique). OBJECTIVES: To test the null hypothesis of no difference in the incidence of damage or disease of the nerve of the tooth (pulp), progression of decay and longevity of restorations irrespective of whether the removal of decay had been minimal (ultraconservative) or complete. SEARCH STRATEGY: The Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed and EMBASE databases were searched. The reference lists in relevant papers were checked. SELECTION CRITERIA: Randomised controlled trials and controlled clinical trials comparing minimal (ultraconservative) caries removal with complete caries removal in unrestored permanent and deciduous teeth. DATA COLLECTION AND ANALYSIS: Outcome measures recorded were exposure of the nerve of the tooth (pulp) during caries removal, patient experience of symptoms of pulpal inflammation or necrosis, progression of caries under the filling, time until the filling was lost or replaced. Due to the heterogeneity of the included studies the overall estimate of effect was calculated using a random-effects model. MAIN RESULTS: Four studies met the inclusion criteria; two stepwise excavation studies and two ultraconservative caries removal studies. Partial caries removal in symptomless, primary or permanent teeth reduces the risk of pulp exposure. We found no detriment to the patient in terms of pulpal symptoms in this procedure and no reported premature loss or deterioration of the restoration. AUTHORS' CONCLUSIONS: The results of this systematic review reject the null hypothesis of no difference in the incidence of damage or disease of the nerve of the tooth (pulp) irrespective of whether the removal of decay had been minimal (ultraconservative) or complete and accepts the null hypothesis of no difference in the progression of decay and longevity of restorations. However, the number of included studies is small and differ considerably. Partial caries removal is therefore preferable to complete caries removal in the deep lesion, in order to reduce the risk of carious exposure. However, there is insufficient evidence to know whether it is necessary to re-enter and excavate further but studies that have not re-entered do not report adverse consequences.

Cariostatic Agents↗
PubMed2006

Centralisation of a hypospadias repair service--the Warwickshire experience.

An audit of the hypospadias repair service provided in the county of Warwickshire has shown that centralising all referrals to a single surgeon who uses limited, well-practiced techniques, greatly improves outcome. Comparison to previous audit of the service, when provided by a number of surgeons in the region, shows complication rates dropping - fistulae occurrence reducing from 35.8% to 6.7% and urethral stricture rates showing similar improvement from 4.4% to 0%. Overall productivity increased, and referral out of region dropped from 13% to 0%. This provides definitive evidence that restructuring of a service already in place has decreased morbidity and increased efficiency to give results comparable to published data.

Child, Preschool↗
PubMed2006

Systematic review of the effectiveness and cost-effectiveness of HealOzone for the treatment of occlusal pit/fissure caries and root caries.

OBJECTIVES: To assess the effectiveness and cost-effectiveness of HealOzone (CurOzone USA Inc., Ontario, Canada) for the management of pit and fissure caries, and root caries. The complete HealOzone procedure involves the direct application of ozone gas to the caries lesion on the tooth surface, the use of a remineralising solution immediately after application of ozone and the supply of a 'patient kit', which consists of toothpaste, oral rinse and oral spray all containing fluoride. DATA SOURCES: Electronic databases up to May 2004 (except Conference Papers Index, which were searched up to May 2002). REVIEW METHODS: A systematic review of the effectiveness of HealOzone for the management of tooth decay was carried out. A systematic review of existing economic evaluations of ozone for dental caries was also planned but no suitable studies were identified. The economic evaluation included in the industry submission was critically appraised and summarised. A Markov model was constructed to explore possible cost-effectiveness aspects of HealOzone in addition to current management of dental caries. RESULTS: Five full-text reports and five studies published as abstracts met the inclusion criteria. The five full-text reports consisted of two randomised controlled trials (RCTs) assessing the use of HealOzone for the management of primary root caries and two doctoral theses of three unpublished randomised trials assessing the use of HealOzone for the management of occlusal caries. Of the abstracts, four assessed the effects of HealOzone for the management of occlusal caries and one the effects of HealOzone for the management of root caries. Overall, the quality of the studies was modest, with many important methodological aspects not reported (e.g. concealment of allocation, blinding procedures, compliance of patients with home treatment). In particular, there were some concerns about the choice of statistical analyses. In most of the full-text studies analyses were undertaken at lesion level, ignoring the clustering of lesions within patients. The nature of the methodological concerns was sufficient to raise doubts about the validity of the included studies' findings. A quantitative synthesis of results was deemed inappropriate. On the whole, there is not enough evidence from published RCTs on which to judge the effectiveness of ozone for the management of both occlusal and root caries. The perspective adopted for the study was that of the NHS and Personal Social Services. The analysis, carried out over a 5-year period, indicated that treatment using current management plus HealOzone cost more than current management alone for non-cavitated pit and fissure caries (40.49 pounds versus 24.78 pounds), but cost less for non-cavitated root caries ( 14.63 pounds versus 21.45 pounds). Given the limitations of the calculations these figures should be regarded as illustrative, not definitive. It was not possible to measure health benefits in terms of quality-adjusted life-years, due to uncertainties around the evidence of clinical effectiveness, and to the fact that the adverse events avoided are transient (e.g. pain from injection of local anaesthetic, fear of the drill). One-way sensitivity analysis was applied to the model. However, owing to the limitations of the economic analysis, this should be regarded as merely speculative. For non-cavitated pit and fissure caries, the HealOzone option was always more expensive than current management when the probability of cure using the HealOzone option was 70% or lower. For non-cavitated root caries the costs of the HealOzone comparator were lower than those of current management only when cure rates from HealOzone were at least 80%. The costs of current management were higher than those of the HealOzone option when the cure rate for current management was 40% or lower. One-way sensitivity analysis was also performed using similar NHS Statement of Dental Remuneration codes to those that are used in the industry submission. This did not alter the results for non-cavitated pit fissure caries as the discounted net present value of current management remained lower than that of the HealOzone comparator ( 22.65 pounds versus 33.39 pounds). CONCLUSIONS: Any treatment that preserves teeth and avoids fillings is welcome. However, the current evidence base for HealOzone is insufficient to conclude that it is a cost-effective addition to the management and treatment of occlusal and root caries. To make a decision on whether HealOzone is a cost-effective alternative to current preventive methods for the management of dental caries, further research into its clinical effectiveness is required. Independent RCTs of the effectiveness and cost-effectiveness of HealOzone for the management of occlusal caries and root caries need to be properly conducted with adequate design, outcome measures and methods for statistical analyses.

Adolescent↗
PubMed2005

Experience of clinical trials in general dental practice.

There is considerable debate about the feasibility and appropriateness of research in dental primary care, particularly the conduct of clinical trials compared with other research designs. While an evidence-based approach to clinical practice is advocated to improve patient care, research relevant to primary care is sparse, with a gap between research findings and clinical practice. Conducting research in a primary care setting is important, while recruitment and retention methods are crucial for generalizability of the results. Systematic reviews show that high-quality trials provide more reliable outcomes, due to methods such as concealment of allocation to groups, blinding, and particularly outcome assessment and loss to follow-up. Our experience of clinical trials in general dental practice has given insight into the design and conduct that ensure feasibility and generalizability. However, only with adequate funding, good infrastructure, and networks can research be conducted in dental primary care.

Dental Research↗
PubMed2005

Alveolar bone grafting: achieving the organisational standards determined by CSAG, a baseline audit at the Birmingham Children's Hospital.

INTRODUCTION: Birmingham Children's Hospital (BCH) is the centre for a regional comprehensive cleft service attempting to implement the national guidelines for minimum standards of care. A national audit of cleft management (CSAG) found that 58% of alveolar bone grafts were successful; published series suggest that success rates can be of the order of 95%. We present the results of an audit of alveolar bone grafting over a 33-month period, after implementation. PATIENTS AND METHODS: A retrospective clinical process audit was taken from the hospital notes and an analysis of radiological outcome by Bergland score was obtained by two independent assessors. RESULTS: The audit highlighted the difficulties of integrating the increased clinical workload. Other difficulties included poorly standardised pre- and postoperative occlusal radiography, inconsistent orthodontic management and a lack of prospective data collection. An 81% success rate for alveolar bone grafting compares favourably to the CSAG study. Of 82 patients, 68 had sufficient data for a retrospective review; 21 were our own patients and 47 were referred into the centralised service. The success of bone grafting as defined by CSAG (including Bergland scores) is based on only two-thirds of the patients as many have their orthodontic treatment managed in more distant units and radiographs are much harder to obtain. Bone grafting later than age 11 years, was true for 28% (6/21) of our BCH patients and 46% (22/47) for those referred to our service. CONCLUSIONS: This audit demonstrates what has been achieved in a re-organised service in the context of Real Politik in the NHS and suggests the areas that require improvement.

Adolescent↗
PubMed2003

Studies of protein-ligand interactions by NMR.

Solution-state NMR has become an accepted method for studying the structure of small proteins in solution. This has resulted in over 3000 NMR-based co-ordinate sets being deposited in the Protein Databank. It is becoming increasingly apparent, however, that NMR is also a very powerful tool for accessing interactions between macromolecules and various ligands. These interactions can be assessed at a wide variety of levels, e.g. qualitative screening of libraries of pharmaceuticals and 'chemical shift mapping'. Dissociation constants can sometimes be obtained in such cases. Another example would be the complete three-dimensional structure determination of a protein-ligand complex. Here we briefly describe a few of the principles involved and illustrate the method with recent examples.

Bacterial Proteins↗
PubMed2003

The dental management of adult patients with haemophilia and other congenital bleeding disorders.

The management of adult dental patients with congenital bleeding disorders has caused a considerable number of problems to the dental profession. There is a need to simplify the process and identify what can be safely carried out on a 'shared care' basis in General Dental Practice or the Community Dental Service. Particular problems are discussed with special reference to those requiring hospital care. The Scottish Oral Health Group for Medically Compromised Patients has developed this clinical guidance in conjunction with the Scottish Haemophilia Directors. It is important that dental care is easily available for this group of patients, especially those living at some distance from the regional centres. The aim is to simplify planning dental care for this group of patients and remove a number of myths concerning their management. The hospital departments, both medical and dental, must be available for advice and to arrange for treatment that is inappropriate outside a specialist hospital.

Adult↗
PubMed2002

What Scottish primary care researchers are doing to recover their standing in the UK.

OBJECTIVE: To compare the outputs of Scottish PC research with the rest of the UK. DESIGN: Bibliometric analysis of the research level and potential impact of research publications. Papers are categorised by level (RL) from basic research to clinical observation and potential impact category (PIC), a 5 year impact factor on a numerical scale. SETTING: Interrogation of the Wellcome Trust's Research Outputs Database 1988-97. SUBJECTS: 17,303 papers, 2,280 arising from Scottish primary care. RESULTS: Scottish primary care publications totalled 14% of the published research in the UK during 1988, by 1997 it had fallen to 10%. PC researchers in the rest of the UK produced a 60% increase (1169 to 1866 per annum) in publications compared to our 25% increase (201 to 251 per annum) over the same period. Scottish papers were less likely to be presenting basic science. The mean potential impact was slightly lower than the rest of the UK (1.89 compared to 1.94, s.e.m.0.02). CONCLUSION: Scottish PC research outputs grew more slowly than the rest of the UK during 1988-97. The research interests and journals selected by the research community contributed to this pattern. The climate, infrastructure and skills required for more effective PC research during this period were also significant factors. The Scottish School of Primary Care provides a mechanism for everyone in NHSScotland and Higher Education Institutions to address the underlying issues identified in this analysis. As a 'baseline' analysis, this report will allow progress to be monitored as the SSPC becomes increasingly effective.

Bibliometrics↗
PubMed2001

NMR studies of the interactions of SpoIIAA with its partner proteins that regulate sporulation in Bacillus subtilis.

SpoIIAA is a key component in the network of interactions that regulate the first sporulation-specific transcription factor, sigma(F), in Bacillus subtilis. In its unphosphorylated form SpoIIAA is either phosphorylated by or forms a non-covalent complex with SpoIIAB, whereas in its phosphorylated form it is dephosphorylated by SpoIIE. In this work we present NMR studies of the SpoIIAA(2).SpoIIAB complex and of mutant proteins that are deficient in their ability to interact with SpoIIAB or SpoIIE. The NMR studies of the SpoIIAA(2).SpoIIAB complex allowed us to define a contiguous patch that is perturbed upon complex formation. By examining the chemical shift perturbations in the mutant proteins we have identified more specific areas that contain residues critical for the SpoIIAB and SpoIIE interactions.

Adenylyl Imidodiphosphate↗
PubMed2001

UV Raman evidence of a tyrosine in apo-human serum transferrin with a low pK(a) that is elevated upon binding of sulphate.

The binding of sulphate to human serum apo-transferrin has been examined by ultraviolet absorption and ultraviolet resonance Raman difference spectroscopies between pH 6.0 and 9.0. The ultraviolet absorption data reveals a negative feature at 245 nm that increases in magnitude with pH, with an apparent pK(a) of 7.57, which the Raman difference data reveals to be due to tyrosine. The pK(a) of this tyrosine is unusually low and is measured at 7.84 by the Raman difference method and is elevated to greater than 9.0 upon addition of sulphate. Previous studies on the N-lobe imply that Tyr 188 is the tyrosine with a low pK(a) and also that Arg 124 is the primary binding site for the sulphate. The functional relevance may be that with sulphate bound, both carbonate binding and the deprotonation of Tyr will be disfavoured, and as a result so is iron binding.

Apoproteins↗
PubMed2001

UV resonance Raman study of streptavidin binding of biotin and 2-iminobiotin: comparison with avidin.

UV resonance Raman (UVRR) spectroscopy is used to study the binding of biotin and 2-iminobiotin by streptavidin, and the results are compared to those previously obtained from the avidin-biotin complex and new data from the avidin-2-iminobiotin complex. UVRR difference spectroscopy using 244-nm excitation reveals changes to the tyrosine (Tyr) and tryptophan (Trp) residues of both proteins upon complex formation. Avidin has four Trp and only one Tyr residue, while streptavidin has eight Trp and six Tyr residues. The spectral changes observed in streptavidin upon the addition of biotin are similar to those observed for avidin. However, the intensity enhancements observed for the streptavidin Trp Raman bands are less than those observed with avidin. The changes observed in the streptavidin Tyr bands are similar to those observed for avidin and are assigned exclusively to the binding site Tyr 43 residue. The Trp and Tyr band changes are due to the exclusion of water and addition of biotin, resulting in a more hydrophobic environment for the binding site residues. The addition of 2-iminobiotin results in spectral changes to both the streptavidin and avidin Trp bands that are very similar to those observed upon the addition of biotin in each protein. The changes to the Tyr bands are very different than those observed with the addition of biotin, and similar spectral changes are observed in both streptavidin and avidin. This is attributable to hydrogen bond changes to the binding site Tyr residue in each protein, and the similar Tyr difference features in both proteins supports the exclusive assignment of the streptavidin Tyr difference features to the binding site Tyr 43.

Avidin↗
PubMed2001

Bacillus subtilis mutations that alter the pathway of phosphorylation of the anti-anti-sigmaF factor SpoIIAA lead to a Spo- phenotype.

Sigma-F, the first sporulation-specific transcription factor of Bacillus subtilis, is regulated by an anti-sigma factor SpoIIAB, which can also act as a protein kinase that phosphorylates the anti-anti-sigma factor SpoIIAA. The time course of phosphorylation reaction is biphasic, a fact that has been interpreted in terms of a mechanism for sequestering SpoIIAB away from sigmaF and thus allowing activation of sigmaF when needed. Site-directed mutagenesis of SpoIIAA has allowed us to isolate two mutants that cannot activate sigmaF and which are therefore Spo-. The two mutant SpoIIAA proteins, SpoIIAAL61A and SpoIIAAL90A, are phosphorylated with linear kinetics; in addition they are less able to form the stable non-covalent complex that wild-type SpoIIAA makes with SpoIIAB in the presence of ADP. The phosphorylated form of SpoIIAAL90A was hydrolysed by the specific phosphatase SpoIIE at the same rate as wild-type SpoIIAA-P, but the rate of hydrolysis of SpoIIAAL61A-P was much slower. The secondary structure and the global fold of the mutant proteins were unchanged from the wild type. The results are interpreted in terms of a model for the wild type in which SpoIIAB, after phosphorylating SpoIIAA, is released in a form that is tightly bound to ADP and which then makes a ternary complex with an unreacted SpoIIAA. We propose that it is the inability to make this ternary complex that deprives the mutant cells of a means of keeping SpoIIAB from inhibiting sigmaF.

Adenosine Diphosphate↗
PubMed2001

Increasing mouthguards usage among junior rugby and basketball players.

OBJECTIVE: To evaluate a Western Australian mouthguard promotion campaign, launched at the start of the 1997/98 junior rugby union and junior basketball seasons, aimed at increasing mouthguard usage at competition and training. METHOD: A quasi-experimental field design was used to assess the impact of the mouthguard campaign on behavioural change. Observational data were collected pre- and post-campaign on mouthguard usage by players present at a rugby and basketball competition event and at a training session. Junior Australian Rules Football players were used as a control group. RESULTS: Pre-post observational surveys showed a significantly greater increase in mouthguard usage in competition games among rugby union (77% to 84%) and basketball players (23% to 43%) compared with the control group (72% to 73%). All codes showed a post-campaign increase in mouthguard usage at training, but the intervention codes' increases were greater than the control's increase (rugby union: 29% to 40%; basketball: 11% to 36%; football: 34% to 40%). CONCLUSIONS: The campaign had a significant and substantial effect on behaviour and provides evidence of the benefits of leveraging a sponsorship to modify the behaviour of the target group. IMPLICATIONS: This campaign provides a model for promoting mouthguard usage in other sports among junior players.

Adolescent↗
PubMed2000

Ultrasonically enhanced leaching: removal and destruction of cyanide and other ions from used carbon cathodes.

The used carbon cathodes ('Spent Pot Lining', SPL) from aluminium smelting are typically contaminated with F-, CN- and Na+ which must be removed before disposal to produce material which satisfies environmental guidelines in respect of maximum rates of ion release. Leaching of powdered and crushed carbon samples in aqueous solution were studied in the presence and absence of ultrasound. First, it was demonstrated that the total leaching of F-, CN- and Na+ from the carbon powder could be accomplished after approximately 20 min of sonication using ultrasound. Second, carbon particles (< 5 mm) showed leaching characteristics under ultrasound which were in good quantitative agreement with the National River Authority (NRA) test under silent conditions; the former being a much more rapid (approximately 1 h compared to 24 h for the NRA test) but equivalent method to the latter standard test. Third, the removed CN- ions were found to be destroyed in the presence of ultrasound, possibly via the oxidative action of hydrogen peroxide generated by the sonication of water.

Journal Article↗
PubMed1999

Therapeutic vaccination with p24-VLP and zidovudine augments HIV-specific cytotoxic T lymphocyte activity in asymptomatic HIV-infected individuals.

This study evaluates the impact of therapeutic vaccination with p24-VLP and zidovudine on the induction or maintenance of HIV-specific cytotoxic lymphocyte activity in a cohort of asymptomatic patients with CD4 counts greater than 400 cells/microl. In a dummy, randomized, phase II clinical trial of the therapeutic vaccine, participants were randomized to one of three arms for 6 months: p24-VLP (500 microg) in alum monthly plus zidovudine 200 mg tds, alum adjuvant plus zidovudine, or p24-VLP plus placebo. Subjects were studied for a total of 52 weeks from baseline. Monitoring included viral load, CD4 and CD8 counts, markers of immune activation, delayed-type hypersensitivity (DTH) skin testing, and cytotoxic T lymphocyte (CTL) measurement. The nine subjects who received p24-VLP and zidovudine had an augmentation and/or broadening of their CTL response compared with baseline (p = 0.004). The eight subjects receiving p24-VLP and seven subjects receiving zidovudine did not have a statistically significant increase or broadening of CTL activity. The augmentation of the CTL response in the subjects who received p24-VLP and zidovudine was not associated with a decline in viral load or an increase in CD8 counts. This study suggests that HIV-specific CTL activity can be augmented in HIV-infected individuals receiving p24-VLP and zidovudine, supporting the hypothesis of therapeutic vaccination in the presence of antiretroviral therapy.

AIDS Vaccines↗