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Biomedical subjects

P Sharpe

Publications and source records attributed to P Sharpe.

At least 37 records · Page 2Linked to original sources
PubMed1999

Estramustine reversal of resistance to intravesical epirubicin chemotherapy.

OBJECTIVE: Failure of epirubicin treatment of superficial bladder cancer implies multidrug resistance (MDR) which is common. MDR is characterised by decreased cellular levels of drug. TCC cell lines sensitive to epirubicin and resistant to both epirubicin and mitomycin C were used to investigate augmented therapy by adding the MDR reversing agent estramustine to an in vitro model. METHODS: Cells were cultured as monolayers. Fluorescence analysis was performed by flow cytometry and confocal microscopy. Cells were exposed to epirubicin 20 microg/ml for 2 h and increasing amounts of estramustine. Cytotoxicity was determined under similar exposure conditions and MTT culture (dye reduction by live cells) allowed viable biomass to be read optically. RESULTS: Resistant cells accumulated eight times less epirubicin than sensitive cells. Confocal microscopy confirmed this for nuclear uptake. Accumulation in resistant cells can be increased to near-sensitive cell levels using 40 microg/ml estramustine. Image analysis of confocal fluorescence showed a shift from cytoplasm to nucleus. This correlated with increased cytotoxicity. CONCLUSION: Estramustine plus epirubicin chemotherapy can overcome MDR and may achieve more successful tumour killing in vivo. It may also prevent emergence of resistance. Primary TCC culture examination permits detection of sensitive and resistant cells and may predict outcome allowing a more logical treatment selection.

Administration, Intravesical↗
PubMed1999

Comparative study of MSX-2, DLX-5, and DLX-7 gene expression during early human tooth development.

Msx and Dlx family transcription factors are key elements of craniofacial development and act in specific combinations with growth factors to control the position and shape of various skeletal structures in mice. In humans, the mutations of MSX and DLX genes are associated with specific syndromes, such as tooth agenesis, craniosynostosis, and tricho-dento-osseous syndrome. To establish some relationships between those reported human syndromes, previous experimental data in mice, and the expression patterns of MSX and DLX homeogenes in the human dentition, we investigated MSX-2, DLX-5, and DLX-7 expression patterns and compared them in orofacial tissues of 7.5- to 9-wk-old human embryos by using in situ hybridization. Our data showed that MSX-2 was strongly expressed in the progenitor cells of human orofacial skeletal structures, including mandible and maxilla bones, Meckel's cartilage, and tooth germs, as shown for DLX-5. DLX-7 expression was restricted to the vestibular lamina and, later on, to the vestibular part of dental epithelium. The comparison of MSX-2, DLX-5, and DLX-7 expression patterns during the early stages of development of different human tooth types showed the existence of spatially ordered sequences of homeogene expression along the vestibular/lingual axis of dental epithelium. The expression of MSX-2 in enamel knot, as well as the coincident expression of MSX-2, DLX-5, and DLX-7 in a restricted vestibular area of dental epithelium, suggests the existence of various organizing centers involved in the control of human tooth morphogenesis.

Animals↗
PubMed1998

Effects of short-chain fatty acids on primary urothelial cells in culture: implications for intravesical use in enterocystoplasties.

The presence of inflammatory changes and mucopus production in an enterocystoplasty may be similar to the condition of diversion colitis and starvation diarrhea caused by a lack of luminal short-chain fatty acids (SCFAs). We postulate a therapeutic role for intravesical SCFA. Because this treatment will also contact the urothelium, we have assessed the effect on cellular proliferation by utilizing primary urothelial cells in culture. Primary urothelial cells were grown from biopsy samples of normal urothelium obtained intraoperatively. A cocktail of SCFA used in the treatment of diversion colitis was incubated with these cells for time intervals ranging from 30 minutes to 72 hours at drug concentrations ranging from 0.04 to 20 mmol/L butyrate equivalent (BE). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure the residual viable biomass to assess growth inhibition. These experiments were repeated on cells grown on matrigel substrate. The human urothelial cancer line RT112 was likewise exposed to SCFAs to assess selectivity between primary and transformed cells. Primary urothelial cells in culture undergo growth inhibition when exposed to SCFAs. The concentration of SCFAs required to reduce the general biomass by 50% or more (IC> or =50) was 20 mmol/L BE when exposure was for 2 hours or less. When drug exposure was prolonged for 72 hours, the IC> or =50 was 2.5 mmol/L BE. Cells grown on matrigel had their growth similarly inhibited. The IC > or = 50 for the RT112 cell line was 2.5 mmol/L BE after 72 hours of drug incubation. Primary urothelial cells in culture undergo a time- and dose-dependent growth inhibition when exposed to SCFAs. This inhibition is particularly apparent at the higher doses similar to those in use in clinical practice. Cells grown on a matrigel substrate suffer growth attenuation similar to that affecting cells grown on polystyrene plates. In vivo assessment in a rodent intravesical model is advisable before considering instillations in patients.

Cell Division↗
PubMed1998

Patient aggression in a general hospital setting: do nurses perceive it to be a problem?

Aggressive incidents in the general hospital setting have been recognised as problematic for health care workers. Despite an awareness of the problem by nursing staff, there is little known about these incidents. A survey was therefore conducted in a metropolitan tertiary hospital to determine the prevalence and extent of patient aggression in order to direct future management strategies. A survey tool elicited information about the aggressor, factors leading to the incident, the nature of the incident, how it was managed and the outcome. Sixty-eight incidents of aggression were reported over a five-month period; all were reported by nursing staff. The majority of incidents occurred after hours when staff resources were limited. Frequent actions taken by staff to manage aggressive patients were chemical and physical restraint. Nurses identified that many of the incidents were unavoidable despite the aggression management training they had received. This paper outlines strategies taken by the hospital to address the issues identified in the survey.

Adolescent↗
PubMed1998

Effects of design changes on cemented tapered femoral stem fixation.

The effects of matte finish and modularity on loosening of tapered stems using the same cementing technique were studied prospectively. In 80 patients, 82 cemented Exeter primary stems were implanted at total hip revision by one surgeon using the same surgical and cementing technique throughout the series. The polished stems behaved differently than the matte surfaced stems behaved. Polished stems subsided in the cement mantle an average of 1 mm at 2 years after implantation, but without subsequent loosening of stems at as long as 12 years after implantation. Matte surfaced stems with metal centralizers had a higher loosening rate, and loss of fixation at the prosthesis to cement interface was identified as an early sign of loosening of these stems. At a mean 6-year followup, there were no revisions nor was there radiographic evidence of loosening of the polished modular stems. It is concluded that matte finish results in increased loosening of tapered stems but the introduction of modularity did not.

Aged↗
PubMed1998

Intravesical chemotherapy with gamma linolenic acid becomes a realistic prospect in serum-free applications: in vitro cytotoxicity and systemic absorption studies.

PURPOSE: To assess the cytotoxicity of Meglumine gamma linolenic acid (MeGLA) in serum-free application on 2 urothelial cancer cell lines, to examine whether the instant kill action of MeGLA is retained in a serum free environment, and to study the pharmacokinetics of intravesical instillation of gamma linolenic acid (GLA). MATERIALS AND METHODS: The 2 human urothelial cancer cell lines (MGH-U1 & RT112) were utilized in classical cytotoxicity assays in which drug exposure lasted 2 hours in serum or in serum-free application. The thiozolyl blue (MTT) assay was used to quantify the residual viable biomass 5 days later. Immediate cytotoxicity was also compared in serum and serum-free application. Four Wistar rats were used to study the intravesical absorption profile of tritiated GLA (3H-GLA). RESULTS: There was a 10-fold enhancement of the lytic efficacy of MeGLA in serum-free application and this enhancement was also observed in experiments assessing instant kill. There was a similar enhancement of efficacy seen in the multi-drug resistant (MDR) clone of cells. The absorption profile showed < 2% of instilled counts were absorbed and the commonest destination for the absorbed GLA was the liver. CONCLUSIONS: The cytotoxic action of MeGLA was enhanced in serum free application. This enhancement was maintained when cells expressed the MDR phenotype. There was limited absorption from the bladder. MeGLA is a feasible intravesical agent for use in superficial bladder cancer.

Administration, Intravesical↗
PubMed1997

Exercise performance and magnetic resonance imaging-determined thigh muscle volume in children.

This study examined the relationships between thigh muscle volume (TMV) and aerobic and anaerobic performance in children. A total of 32 children, 16 boys and 16 girls, aged 9.9 (0.3) years completed a treadmill running test to exhaustion for the determination of peak oxygen uptake (peak VO2) and a Wingate Anaerobic Test (WAnT) for the determination of peak power (PP) and mean power (MP). The volume of the right thigh muscle was determined using magnetic resonance imaging. TMV was not significantly different in boys and girls [2.39 (0.29) l vs 2.18 (0.38) l, P > 0.05]. Peak VO2 and MP were significantly higher in boys than girls (P < 0.01) whether expressed in absolute, mass-related or allometrically scaled terms. Absolute PP was not significantly different in boys and girls but mass-related and allometrically scaled values were higher in boys (P < 0.01). TMV was correlated with absolute peak VO2, PP and MP in both sexes (r = 0.52-0.89, P < 0.01). In boys, mass-related PP was correlated with TMV (r = 0.53, P < 0.01), and in girls mass-related peak VO2 was correlated with TMV (r = -0.61, P < 0.01). However, in neither sex were allometrically scaled peak VO2, PP or MP correlated with TMV (P > 0.05). There were no significant differences between boys and girls in terms of peak VO2, PP or MP when expressed in a ratio to TMV or allometrically scaled TMV. In conclusion, this study has demonstrated that, when body size is appropriately accounted for using allometric scaling, TMV is unrelated to indices of aerobic and anaerobic power in 10-year-old children. Furthermore, there appear to be no qualitative differences in the muscle function of boys and girls in respect of aerobic and anaerobic function.

Child↗
PubMed1997

Signalling networks regulating dental development.

There has been rapid progress recently in the identification of signalling pathways regulating tooth development. It has become apparent that signalling networks involved in Drosophila development and development of mammalian organs such as the limb are also used in tooth development. Teeth are epithelial appendages formed in the oral region of vertebrates and their early developmental anatomy resembles that of other appendages, such as hairs and glands. The neural crest origin of tooth mesenchyme has been confirmed and recent evidence suggests that specific combinations of homeobox genes expressed in the neural crest cells may regulate the types of teeth and their patterning. Signalling molecules in the Shh, FGF, BMP and Wnt families appear to regulate the early steps of tooth morphogenesis and some transcription factors associated with these pathways have been shown to be necessary for tooth development. Several of the conserved signals are also transiently expressed in the enamel knots in the dental epithelium. The enamel knots are associated with the characteristic epithelial folding morphogenesis which is responsible for the development of tooth shape and it is currently believed that the enamel knots function as signalling centres regulating tooth shape development. The developing tooth has proven to be an excellent model in studies of the molecular basis of patterning and morphogenesis of organs and it can be expected that continuing studies will rapidly increase the understanding of these mechanisms.

Animals↗
PubMed1996

Vitamin E and exercise in the Northern Ireland population.

Serum vitamin E, vitamin E/cholesterol and physical activity and fitness were examined in a representative cross section (n = 1600) of the Northern Ireland population as part of the Northern Ireland health and activity survey. Serum vitamin E levels were measured by high-performance liquid chromatography, cholesterol by an enzymatic method, physical activity profile was recorded by computer assisted interview and physical fitness was determined by estimation of VO2 max. The levels of serum vitamin E and vitamin E/cholesterol ratio in the Northern Irish population were similar or higher than in other populations with lower incidences of coronary heart disease. The assessment of activity showed that 75% of the population fell below recommended activity levels likely to confer a cardioprotective effect. A significant relationship (P = 0.01) was found in males between serum vitamin E levels and lifetime participation in physical activity. Otherwise no relationship was found between serum vitamin E or vitamin E/cholesterol ratio and physical activity or fitness in the population.

Adolescent↗
PubMed1993

Abdominal fat deposition in 11-year-old children.

Although the metabolic complications accompanying visceral deposition of fat are well-established, the onset and extent of such fat patterning in children has not been fully documented. This has been due to the problem of computerized tomography exposing children to a prohibitive radiation risk. Nuclear magnetic resonance imaging (MRI) has provided a feasible alternative. Specifically, the purposes of this study were to use MRI (i) to assess the extent of intra-abdominal (IA) and subcutaneous abdominal (SA) fat deposition in 11-year-old boys and girls, and (ii) to identify the most useful anthropometric indicators of IA adiposity in children. Twenty-five boys and 25 girls were selected to represent, by quintiles, the body mass index range for their age. IA fat, SA fat, and total cross-sectional areas were measured from an MRI scan at the umbilicus. Body density was assessed by hydrostatic weighing, and skinfold thicknesses, circumferences and related ratios, and stage of sexual maturity were measured. Results showed that a wide variation in IA fat deposition was present with amounts ranging from 6 to 58 cm2 (mean = 17.8 +/- 10.0) for boys and 15 to 50 cm2 (mean = 24.8 +/- 8.8) for girls. Percentage of cross-sectional area taken up by visceral fat appears to be less than in normal weight adults. Fourteen children had intra-abdominal/subcutaneous abdominal fat ratios that have been associated with higher health risk in obese adults. Waist-hip circumference ratio (WHR), which is widely used as an indicator of IA deposition in adults, was not a useful predictor in these children.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1987

Image quality of abdominal computed tomography in the elderly.

The hard copy images of 96 randomly selected patients ranging in age from 45 to 84 years who underwent routine abdominal computed tomography (CT) have been assessed. There was little variation in image quality with age although the best images were found in the younger men. The worst images were obtained in the younger women. Advanced age is not, by itself, a contra-indication for good quality abdominal CT on a modern unit.

Age Factors↗
PubMed1987

The effectiveness of tactile stimulation as a form of early intervention: a quantitative evaluation.

The results of studies examining the effectiveness of tactile stimulation as a form of sensory enrichment for infants and young children were analyzed by the use of recently developed quantitative methods that treat research synthesis as a unique type of scientific inquiry. Nineteen studies meeting certain predetermined criteria were included in the review. The 19 studies contain 103 statistical hypothesis tests that evaluated the effectiveness of tactile stimulation programs. Analysis of these tests, based on the calculation of effect sizes, revealed that subjects receiving some form of controlled tactile stimulation performed better on a variety of dependent measures than subjects not receiving intervention. Larger treatment effects were associated with pre-experimental designs, and also with studies in which the internal validity was rated as poor. Several other study characteristics, such as how the subjects were assigned to conditions and how the dependent measure was recorded, were related to study outcome as measured by effect size. The results indicate that an accurate interpretation of tactile stimulation studies cannot be made without consideration of specific design variables and study characteristics.

Child Development↗
PubMedDate not supplied

Factors associated with weight change among clients of a residential weight control program indicating binge and nonbinge traits.

The long-term effects of a 12- and 26-day residential weight control program on weight change were determined in 187 men and women, 1 to 5 years after treatment. Subjects completed a paper/pencil questionnaire assessing current diet, weight control techniques, exercise behaviors, behavior modification techniques, binge eating, and dieting behavior. General linear modeling was used to investigate the association between behaviors maintained posttreatment and current weight among subjects who demonstrated behaviors indicative of binge traits (BT) and nonbinge traits (NBT). Results indicate that dissimilar variables are predictive of weight change in the BT and NBT groups. Engaging in exercise behaviors and reduced attempts at dieting lead to greater weight loss in NBT individuals. The use of preplaning techniques was found to be indicative of greater weight loss in BT individuals. These findings suggest the importance of identifying individuals who indulge in binge-eating behaviors prior to intervention in order to deliver the appropriate treatment methods.

Adult↗
PubMedDate not supplied

Longitudinal changes in isokinetic leg strength in 10-14-year-olds.

This study used multilevel regression modelling to longitudinally investigate the influences of age, sex, body size, skinfold thicknesses and maturity on the development of isokinetic knee extension and flexion on eight occasions over a 4-year period. Forty-one subjects (20 boys and 21 girls) were measured and 295 isokinetic leg strength tests and associated measures were successfully completed. Subjects were aged 10.0 +/- 0.3 years at the onset of the study. Stature, body mass, triceps and subscapular skinfold thicknesses, and sexual maturation (according to pubic hair development) were assessed at each test occasion. Isokinetic concentric knee extension and flexion of the dominant leg were determined to elicit maximal peak extension (PET) and flexion torque (PFT). Statistical significance was accepted at p < 0.05. Multilevel regression modelling indicated that stature and mass were significant predictors of both PET and PFT. Age and maturity were non-significant explanatory variables once stature and mass had been accounted for. Skinfold thickness exerted a significant negative effect independent of mass and stature on PFT but not PET. At test occasion 8, cross-sectional areas (CSAs) of the knee extensors (ExCSA) and flexors (FlexCSA) were determined using magnetic resonance imaging on 23 boys and 14 girls and examined as predictors of isokinetic leg strength. There were no significant sex-related differences in PET or PFT. Pearson product moment correlation coefficients indicated a significant relationship between ExCSA and PET and FlexCSA and PFT for both boys and girls. Analysis of covariance (ANCOVA) demonstrated that ExCSA and FlexCSA were significant explanatory variables for PET and PFT, respectively, but became non-significant once stature and mass had been introduced into the analysis. To conclude, there were no significant sex differences in PET or PFT between the ages of 10 and 14 years and the development of PET and PFT could be accounted for by the increase in stature and mass. Age, maturity and thigh muscle CSA were all non-explanatory variables in the production of PET and PFT once body size had been controlled for.

Adolescent↗
PubMedDate not supplied

An assessment of the cognitive abilities of multiply handicapped children: adaptations of the Uzgiris and Hunt scales and their use with children in Britain and Singapore.

Educational achievement is measured by many forms of assessment. The assessment of some children, and disabled children, has elicited much concern and debate. In particular, problems have arisen with test design, construction, administration and recording. In the West, legislation and public opinion have drawn attention to the need to provide more suitable measuring instruments. The purpose of this paper is to illustrate the use of an adapted assessment procedure for monitoring educational achievement and progress. A study is discussed where the major aim is to use situations which are both stimulating and which most closely resembled the children's natural settings, in order to elicit communication and language skills. The study is being carried out in Singapore with a group of multiply handicapped children. The adaptations to the administration of the test enable the examiner to note the behaviour as it occurs rather than look for expected behaviours. It is possible then to record behaviours at a later stage. The results of the study show that it is possible to elicit the required responses from a group of children who are diagnosed as multiply handicapped and whose competencies are difficult to assess. In the original research in Britain, with a large group of multiply handicapped children, there was evidence of reliability, validity and ordinality in the children's responses. Analysis of these children's scores showed patterns of responses inconsistent with a popular view of development. This paper describes the Singapore study and the original study upon which it is based.

Child↗