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Biomedical subjects

L Shaw

Publications and source records attributed to L Shaw.

At least 19 recordsLinked to original sources

Clinical and economic impact of exercise electrocardiography and exercise echocardiography in clinical practice.

BACKGROUND: Patients with known or suspected coronary disease are often investigated to facilitate risk assessment. We sought to examine the cost-effectiveness of strategies based on exercise echocardiography and exercise electrocardiography. METHODS AND RESULTS: We studied 7656 patients undergoing exercise testing; of whom half underwent exercise echocardiography. Risk was defined with the Duke treadmill score for those undergoing exercise electrocardiography alone, and by the extent of ischaemia by exercise echocardiography. Cox proportional hazards models, risk adjusted for pretest likelihood of coronary artery disease, were used to estimate time to cardiac death or myocardial infarction. Costs (including diagnostic and revascularisation procedures, hospitalisations, and events) were calculated, inflation-corrected to year 2000 using Medicare trust fund rates and discounted at a rate of 5%. A decision model was employed to assess the marginal cost effectiveness (cost/life year saved) of exercise echo compared with exercise electrocardiography. Exercise echocardiography identified more patients as low-risk (51% vs 24%, p<0.001), and fewer as intermediate- (27% vs 51%, p<0.001) and high-risk (22% vs 4%); survival was greater in low- and intermediate-risk and less in high-risk patients. Although initial procedural costs and revascularisation costs (in intermediate-high risk patients) were greater, exercise echocardiography was associated with a greater incremental life expectancy (0.2 years) and a lower use of additional diagnostic procedures when compared with exercise electrocardiography (especially in lower risk patients). Using decision analysis, exercise echocardiography ( in 2615/life year saved) was more cost effective than exercise electrocardiography. CONCLUSION: Exercise echocardiography may enhance cost-effectiveness for the detection and management of at risk patients with known or suspected coronary disease.

Coronary Artery Disease↗

Intravenous busulfan for allogeneic hematopoietic stem cell transplantation in infants: clinical and pharmacokinetic results.

SUMMARY: High-dose busulfan is an important component of myeloablative regimens. Variable drug exposure may occur following oral administration. Therefore, the use of intravenous busulfan has been advocated. Previous work has suggested a cumulative dosage of 16 mg/kg for haematopoietic transplantation in children less than 3 years of age, but only limited data are available in infants. Pharmacokinetics of intravenous busulfan administered at the suggested dosage were studied in 14 infants (median age 4.7 months). Busulfan plasma concentrations were measured by either GC-MS or HPLC-UV. In seven patients, the dose was decreased to target an area- under- the- curve of 600-1300 micromol min. The median total dose given was 13.8 mg/kg. All patients engrafted. Severe veno-occlusive disease occurred in one patient. Our study demonstrates that a cumulative dosage of 16 mg/kg is associated with higher exposure than expected in infants. We suggest an initial dose of 0.8 mg/kg followed by pharmacokinetically guided dose adjustment.

Area Under Curve↗

Pneumococcal nasopharyngeal carriage in children following heptavalent pneumococcal conjugate vaccination in infancy.

AIMS: To ascertain whether the reduction in nasopharyngeal carriage of vaccine serotypes induced by pneumococcal conjugate vaccine (PnCV) administered to infants persists beyond the age of 2 years. METHODS: Non-randomised, unblinded controlled study of 2-5 year old children who had received three doses of heptavalent PnCV (7VPnCV) in infancy and 23-valent pneumococcal polysaccharide vaccine at 13 months, and unimmunised controls. Nasopharyngeal swabs were taken in summer (150 vaccinated subjects, 126 controls) and winter (143 vaccinated subjects, 188 controls). The swabs were cultured and serotyped for Streptococcus pneumoniae. RESULTS: Carriage rates (vaccinated subjects: 24.7% and 43.4%; controls: 27.0% and 41.0%, in summer and winter respectively) and carriage of vaccine serotypes (subjects: 10.0% and 30.0%; controls: 13.5% and 31.5%, in summer and winter respectively) were similar in the two groups. CONCLUSIONS: Effects of vaccination in infancy on rates of nasal carriage of pneumococcus and serotype replacement in children living in a largely unvaccinated population are no longer evident by 2-5 years of age.

Anti-Bacterial Agents↗

Dental erosion in a group of British 14-year-old, school children. Part III: Influence of oral hygiene practises.

OBJECTIVES: The aims of this study were firstly to describe the dental history and oral hygiene practises in a cluster random sample of 14-year-old children in Birmingham, UK. The second aim was to determine whether the oral hygiene practises are associated with dental erosion. METHOD: A total of 418, 14-year-old schoolchildren from a cluster random sample in Birmingham, UK were assessed for dental erosion (209 males and 209 females). Data on the dental history and oral hygiene practises were obtained from a self-reported questionnaire supplemented by a structured interview. The data were analysed using SPSS with Mann-Whitney U analyses and odds ratios. RESULTS: 74% of the teenagers claimed to attend the dentist on a six-monthly basis; 60% brushed their teeth twice a day ie before breakfast and last thing at night, 25% once a day, 12% three times or more a day and 3% less than once a day. It was a so found that 28% of the children brushed their teeth after meals; 92% of the children used a manual toothbrush and 56% of them replaced their toothbrush every three-months. The most common technique used by the children was a circular brushing movement; 44% of them used a mouthwash and 40% used other interdental cleaning. Girls brushed their teeth more frequently than boys. Associations were found between dental erosion and brushing teeth last thing at night, after meals, techniques of brushing teeth, and type of toothbrush and frequency of brushing. It was concluded that reported oral hygiene practises in teenage schoolchildren in Birmingham, UK complied with generally recommended guidelines. However, there was an association between dental erosion and some of these oral hygiene practises. Advice concerning the impact of some oral hygiene procedures needs to be given to those who are susceptible to dental erosion.

Adolescent↗

Is there a relationship between asthma and dental erosion? A case control study.

OBJECTIVES: The aims of this study were firstly to assess and compare the prevalence of dental erosion and dietary intake between three groups of children; children with asthma, those with significant tooth erosion but with no history of asthma, and children with no history of asthma or other medical problems. Secondly, to discover whether there was a relationship between medical history and dietary practises of these children and the levels of dental erosion. Thirdly, to measure and compare their salivary flow rates, pH and buffering capacity. METHODS: The study consisted of 3 groups of children aged 11-18 years attending Birmingham Dental Hospital: 20 children with asthma requiring long-term medication, 20 children referred with dental erosion, and 20 children in the age and sex matched control group. Tooth wear was recorded using a modification of the tooth wear index (TWI) of Smith and Knight. Data on the medical and dietary history were obtained from a self-reported questionnaire supplemented by a structured interview. The salivary samples were collected under standard methods for measurements. RESULTS: Fifty percent of the children in the control group had low erosion and 50% moderate erosion. However, high levels were recorded in 35% of children in the asthma group and 65% in the erosion group. There appeared to be no overall differences in diet between the groups. There was an association between dental erosion and the consumption of soft drinks, carbonated beverages and fresh fruits in all the three groups. More variables related to erosion were found in the erosion and asthma groups. A comparison between the three groups showed no significant differences in unstimulated and stimulated salivary flow rates, or pH and buffering capacity. CONCLUSION: There were significant differences in the prevalence of erosion between the three groups, children with asthma having a higher prevalence than the control group. Although there was a relationship between the levels of erosion and some medical history and acidic dietary components, these did not explain the higher levels in asthmatic children. Further investigation is required into the factors affecting the increased prevalence of erosion in children with asthma.

Adolescent↗

Cytomegalovirus and cyclosporin-induced gingival overgrowth in children with liver grafts.

OBJECTIVE: To determine whether cytomegalovirus (CMV) is associated with gingival overgrowth in paediatric liver graft recipients treated with cyclosporin. STUDY DESIGN: Thirty-four children, 25 of whom were under 5 years of age, who had undergone liver transplantation, were examined. An Index of Severity of Gingival Overgrowth was used to measure the prevalence and severity of the gingival overgrowth. The trough cyclosporin level was recorded and the CMV status of the patient matched to the dental findings. The association between the severity of gingival overgrowth and CMV infection was examined using the contingency coefficient. An anova was used to assess the association between the circulating trough cyclosporin concentration and the severity of gingival overgrowth. Pearson's Product Moment Correlation Coefficient was used to examine the association between the duration of exposure to cyclosporin and the severity of gingival overgrowth. RESULTS: There was a significant inverse association between the duration of exposure to cyclosporin and the severity of gingival overgrowth. There was no relationship between the trough cyclosporin concentration and the severity of gingival overgrowth. There was no association between CMV and gingival overgrowth. CONCLUSION: Gingival overgrowth was related to the duration of cyclosporin therapy but was neither more prevalent nor more severe in subjects who were CMV seropositive.

Analysis of Variance↗

Investigation of the effect of FK506 (tacrolimus) and cyclosporin on gingival overgrowth following paediatric liver transplantation.

INTRODUCTION: Gingival overgrowth associated with immunosuppression following liver transplantation is a commonly recognized clinical problem. The aims of this study were to determine the incidence of gingival overgrowth in a group of children post liver transplantation and to compare gingival overgrowth in children receiving FK506 with those receiving cyclosporin. METHODS: Seventy-nine children (aged 15-196 months) undergoing liver transplantation at Birmingham Children's Hospital between October 1998 and October 2000 were studied. Gingival overgrowth was assessed in a blinded fashion and scored in a previously validated manner. Gingival overgrowth scores of the patients on each immunosuppressant drug were then compared. RESULTS: Fifty-two patients were treated with cyclosporin and 27 treated with tacrolimus. Eighteen children were also receiving nifedipine (also known to cause gingival overgrowth) and were considered separately. Of the 41 children receiving cyclosporin alone, 26 exhibited gingival overgrowth compared to zero of 20 patients receiving tacrolimus alone. Those children treated with immunosuppression plus nifedipine developed gingival overgrowth, however, this was much less marked in the tacrolimus group. CONCLUSION: Tacrolimus, unlike cyclosporin, is not associated with gingival overgrowth when used for immunosuppression following liver transplantation in children, and may be the drug of choice for children.

Adolescent↗

Long-term cytotoxicity of resin-based dental restorative materials.

Highly filled composites, Ormocers (organically modified ceramics) and 'smart' materials have been developed to overcome the polymerization shrinkage problems of conventional composite materials. The purpose of the current study was to investigate the effect of longer-term (up to 8 weeks) ageing of these resin-based dental restorative materials and determine the effect of post-curing on cytotoxicity. Twelve discs of each material (Colombus/IDR, Definite/Degussa, Ariston pHc/Vivadent) were either light-cured (Lc) or light-cured and post-cured (Pc). For cytotoxicity testing, the discs were placed in contact with cell culture medium (DMEM) and incubated at 37 degrees C. Extracts from composite materials were collected after 24 h and weekly over a time period of 8 weeks. Cytotoxicity of the eluates to cultured fibroblasts (Balb/c3T3) were measured by the succinic dehydrogenase (SDH) activity (MTT assay) and the results expressed in percentage of negative controls (Teflon discs). The results showed that ageing significantly influenced the cytotoxicity of the materials. Except for Ariston pHc, materials were less cytotoxic after 8 weeks of ageing than they were in early intervals and post-curing was not generally useful in reducing cytotoxicity. The Ariston pHc was initially moderately toxic, but then become highly cytotoxic for 5 weeks before returning to initial levels. The current study demonstrated the importance of assessing the cytotoxicity of resin composite materials at multiple times.

3T3 Cells↗

Tooth surface pH during drinking of black tea.

OBJECTIVES: To investigate the composition of black tea in terms of its erosive potential. To determine the pH profile at the palatal surface of anterior and posterior sites of the dentition after drinking black tea. METHODS: Tea solution was analysed for its pH and anion composition to provide information on its acid content. A group of ten healthy subjects, aged 21-23 years were monitored for tooth surface pH on the palatal aspects of the maxillary anterior dentition and the maxillary molar dentition after drinking tea using a micro-pH electrode mounted on a vinyl splint. RESULTS: The pH of the tea solution was 4.9 and the major anions detected were oxalate and citrate. Tooth surface pH monitoring indicated that only small decreases in pH of less than 1 pH unit were observed after drinking tea and the minimum mean pH reached was 5.45. Maximum decrease in pH was observed after 20-25 seconds and resting pH levels were restored within approximately 2 minutes after drinking. CONCLUSION: The pH and anion profile of black tea are indicative of low acid composition. The very small pH decreases observed at the tooth surface after drinking tea indicate that it may be safely recommended as a substitute for more acidic drinks as a part of preventive measures for dental erosion.

Adult↗

Dental erosion in a group of British 14-year-old school children. Part II: Influence of dietary intake.

OBJECTIVES: The aims of the present study were first to investigate the dietary intake pattern of UK teenagers and secondly to determine the relationship, if any, between dental erosion and dietary intake in these children. METHODS: The study group consisted of a cluster random sample of 14-year-old school children in Birmingham, UK: 418 children were examined from 12 different schools; 209 were male and 209 female. Data on the rate and frequency of consumption of drinks, foods, and fruits were obtained from a self-reported questionnaire supplemented by a structured interview. The data were analysed using SPSS with Chi-square, and Spearman correlation analysis. RESULTS: Over 80% of the teenagers regularly consumed soft drinks but approximately half of these children had a relatively low weekly consumption. However, 13% and 10% respectively had more than 22 intakes per week of cola and other carbonated drinks. Almost a quarter of these 14-year-olds had alcoholic drinks, with significantly more males than females involved (Chi-square P < 0.05) . Girls had a greater intake of fruits. Statistically significant correlations were found between the prevalence of erosion and the consumption of soft drinks, carbonated beverages, alcohol drinks, fresh fruits, Vitamin-C tablets and foodstuffs (Spearman correlation analysis P < 0.05). CONCLUSION: It was concluded that consumption particularly of soft drinks was high and common in teenage school children in Birmingham, UK. In addition there was a relationship between dental erosion and acidic dietary intake. Further investigation of the erosive potential of these drinks and foods is required.

Adolescent↗

Dental erosion in a group of British 14-year-old, school children. Part I: Prevalence and influence of differing socioeconomic backgrounds.

OBJECTIVES: To establish the prevalence of erosion in a cluster random sample of 14- year-olds in Birmingham UK. To determine whether socioeconomic group influences the prevalence of erosion. METHODS: The study group consisted of a cluster random sample of 14-year-old school children in Birmingham UK: 418 children were examined from 12 different schools; 209 were male and 209 female. The level of tooth wear was recorded using a modification of the (TWI) index of Smith and Knight (1984). The ACORN classification was used to assess the socioeconomic status of all children. RESULTS: Results showed that 48% of the children had low erosion, 51% had moderate erosion and only 1% had severe erosion. There were statistically significant differences between males and females; more males had buccal/labial and lingual/palatal tooth surface erosion than females (Chi-square analysis P < 0.001). There was also significantly more erosion observed in teenagers in the lowest socioeconomic categories. CONCLUSION: It was concluded that moderate levels of dental erosion are common in 14-year-old school children and this may lead to increasing clinical problems. There was significantly more erosion in children from low socioeconomic groups. Possible aetiological factors need to be investigated further.

Adolescent↗

Characterization of the MHC class I region of the Japanese pufferfish (Fugu rubripes).

A BAC map of the Japanese pufferfish (Fugu) MHC class I region was constructed using a mixture of sequence scanning and sequence-tagged site mapping methodologies. The Fugu MHC class Ia genes are linked to genes which are found within the human classical MHC class II and extended class II regions, a situation which has been found in the MHC of all teleosts mapped so far. The 300-kb contig comprises 24 MHC-related genes and is bounded by six non-MHC genes, which are thought to represent an evolutionary breakpoint within the region. Comparative analysis with both human and zebrafish MHC maps indicates two blocks of genes (KNSL2, ZNF297, DAXX, TAPBP, FLOTILLIN; and PSMB8, PSMB10, PSMB9, ABCB3, FABGL, BRD2, COL11A2, RXRB) which have remained linked over 400 million years and may represent an ancestral arrangement of the vertebrate MHC. Zebrafish and Fugu diverged between 100-200 million years ago and differences exist between these two fish species. The position and number of MHC class Ia genes is not conserved between species, there is an inversion of a block of nine genes centering on the PSMB cluster, and additional genes are present in zebrafish coding for a transport-associated protein and a beta proteasome subunit. The extent of these differences has implications for the extrapolation of fish model organism data to commercial aquaculture species. The data presented here represent the most extensive analysis of a fish MHC class Ia region described so far and clearly delimit the extent of this region in Fugu and, potentially, all teleosts.

Animals↗

The bio-availability of fluoride from black tea.

OBJECTIVES: To investigate the oral retention of fluoride from tea and its association with the tooth surface and acquired pellicle. METHODS: Oral retention of fluoride after rinsing in vivo was assessed from expectorated samples with an ion specific electrode methodology. Interaction of fluoride with the tooth surface and acquired pellicle was examined in situ with enamel blocks mounted on partial removable appliances. In vitro models were used to examine fluoride binding to enamel particles. RESULTS: Thirty four percent of the fluoride was retained in the oral cavity after rinsing with tea. Differences in retention at the tooth surface in the presence and absence of an acquired pellicle were not statistically significant at incisor or molar sites. Fluoride from tea showed strong binding to enamel particles, which was only partially dissociated by solutions of ionic strength considerably greater than that of saliva. Binding studies demonstrated strong avidity of enamel for tea and salivary pellicle components. CONCLUSIONS: This study has demonstrated that tea can provide an effective vehicle for fluoride delivery to the oral cavity where it may interact with the oral tissues and their surface integuments. This may lead to local topical effects of the ingested fluoride as well as systemic effects following oral and gastro-intestinal absorption.

Adult↗

N-Glycolylneuraminic acid in human tumours.

N-Glycolylneuraminic acid (Neu5Gc) is an abundant sialic acid, occurring in the glycoconjugates of most deuterostome animals. Homo sapiens is a notable exception, since Neu5Gc is effectively absent from normal human tissues. This is due to a deletion in the human gene coding for CMP-Neu5Ac hydroxylase, the enzyme usually responsible for Neu5Gc biosynthesis. Despite this mutation, persistent reports in the literature suggest that Neu5Gc occurs in the glycoconjugates of many human tumours, where it might be responsible for the formation of so-called Hanganutziu-Deicher antibodies. However, the variety of systems studied and the various experimental approaches adopted have yielded a complex picture of Neu5Gc occurrence in human neoplasias. The aim of this paper is therefore to provide a critical review of the evidence for Neu5Gc in human tumours, paying particular attention to the analytical methods employed. The possible clinical applications of Neu5Gc-containing glycoconjugates and Hanganutziu-Deicher antibodies in the diagnosis and treatment of breast cancer and melanoma are also discussed. In view of the lack of CMP-Neu5Ac hydroxylase in human cells, alternative metabolic pathways for the biosynthesis of glycoconjugate-bound Neu5Gc are considered.

Antibodies, Heterophile↗

A comprehensive phylogenetic analysis of Rieske and Rieske-type iron-sulfur proteins.

The Rieske iron-sulfur center consists of a [2Fe-2S] cluster liganded to a protein via two histidine and two cysteine residues present in conserved sequences called Rieske motifs. Two protein families possessing Rieske centers have been defined. The Rieske proteins occur as subunits in the cytochrome bc1 and cytochrome b6f complexes of prokaryotes and eukaryotes or form components of archaeal electron transport systems. The Rieske-type proteins encompass a group of bacterial oxygenases and ferredoxins. Recent studies have uncovered several new proteins containing Rieske centers, including archaeal Rieske proteins, bacterial oxygenases, bacterial ferredoxins, and, intriguingly, eukaryotic Rieske oxygenases. Since all these proteins contain a Rieske motif, they probably form a superfamily with one common ancestor. Phylogenetic analyses have, however, been generally limited to similar sequences, providing little information about relationships within the whole group of these proteins. The aim of this work is, therefore, to construct a dendrogram including representatives from all Rieske and Rieske-type protein classes in order to gain insight into their evolutionary relationships and to further define the phylogenetic niches occupied by the recently discovered proteins mentioned above.

Amino Acid Motifs↗

Effects of the oestrous cycle and gender on acute vasodilatory responses of isolated pressurized rat mesenteric arteries to 17 beta-oestradiol.

The influence of the oestrous cycle and gender on responses of isolated pressurized mesenteric arteries to acute 17 beta-oestradiol was investigated. All vessels, pre-contracted with 60 mM KCl or 10 microM U46619 (9,11 dideoxy-11alpha, 9alpha-epoxy methano-prostaglandin), exhibited concentration-dependent vasodilatory responses to 17 beta-oestradiol (3 - 30 microM). The largest responses were seen in vessels from female rats in pro-oestrous (38.9+/-5.4% U46619 max and 63.1+/-4.0% KCl max for 30 microM oestradiol), the smallest from animals in di-oestrous (20.1+/-3.7% U46619 and 50.1+/-4.5% KCL - both P:<0.05 cf pro-oestrous (all n=8)). Responses of vessels from male rats were similar to those from pro-oestrous rats (41.5+/-9.1% U46619 (n=10) and 54.9+/-2.9% KCl (n =8)). All responsees were unaffected by inhibition of nitric oxide synthase (NOS). Female rats in pro-oestrous had the highest plasma concentrations of 17 beta-oestradiol and testosterone (40.76+/-4.73 pg ml(-1) and 0.29+/-0.05 ng ml(-1) respectively (n=8)) while those in di-oestrous had the lowest (15.24+/-3.94 pg ml(-1) for oestradiol and 0.08+/-0.03 ng ml(-1) for testosterone (n=8)). In male rats the concentration of oestrogen was 10.29+/-1.21 pg ml(-1) (n=7) while that of testosterone was 3.15+/-0.36 ng ml(-1) (n=7). Incubation of arteries isolated from male rats and from female rats in pro-oestrous and di-oestrous with testosterone (1 microM, 3 h) significantly enhanced the subsequent vasodilatory responses to acute 17 beta-oestradiol. Following incubation, the responses to 17 beta-oestradiol were similar in all groups. These observations suggest that gender and the oestrous cycle may influence the vascular responses to acute 17 beta-oestradiol administration.

Animals↗