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Biomedical subjects

M Barker

Publications and source records attributed to M Barker.

At least 37 records · Page 2Linked to original sources
PubMed2001

An interactive computer-animated system (SpiroGame) facilitates spirometry in preschool children.

Although airway disease in preschool children is common, standard spirometry is limited by the level of cooperation. We evaluated a computer-animated system (SpiroGame) aimed at improving children's performance in spirometry. SpiroGame includes a commercial pneumotachograph (ZAN100; ZAN Messgeraete GmbH, Oberthulba, Germany) and games teaching tidal breathing and all steps of an FVC maneuver. SpiroGame was compared with commercial flow-targeted candle-blowing software (MasterLab, Jaeger, Germany), and with extrapolated predicted values. Of 112 children aged 3 to 6 yr, 10 refused spirometry and 102 proceeded to FVC games and were randomized to initially perform either SpiroGame or candle-blowing. Training lasted 5 to 10 min for SpiroGame and 3 to 7 min for candle-blowing. Acceptable spirometry was performed by 69 of 102 children with SpiroGame and 48 of 102 with candle-blowing (p = 0.005). Order did not affect success. Acceptable FEV(1) maneuvers were achieved by 55 children with SpiroGame and two children with candle-blowing. The intrasubject coefficient of variation was 4.0% for FVC and 3.3% for FEV(1) with SpiroGame. A premature expiratory break occurred in 41 subjects with candle-blowing and in six with SpiroGame. FEV(0.5) could be measured with both systems. FVC and maximal midexpiratory flow at 50% of FVC (MMEF(50)) values were similar, whereas peak expiratory flow was higher with candle-blowing. In 39 healthy children, most parameters with SpiroGame were similar to extrapolated normal values. We conclude that an interactive computer-animated system facilitates successful spirometry in preschool children.

Child↗
PubMed2001

HPP1: a transmembrane protein-encoding gene commonly methylated in colorectal polyps and cancers.

Adenomas are the precursors of most colorectal cancers. Hyperplastic polyps have been linked to the subset of colorectal cancers showing DNA microsatellite instability, but little is known of their underlying genetic etiology. Using a strategy that isolates differentially methylated sequences from hyperplastic polyps and normal mucosa, we identified a 370-bp sequence containing the 5' untranslated region and the first exon of a gene that we have called HPP1. Rapid amplification of cDNA ends was used to isolate HPP1 from normal mucosa. Using reverse transcription-PCR, HPP1 was expressed in 28 of 30 (93%) normal colonic samples but in only seven of 30 (23%) colorectal cancers (P < 0.001). The 5' region of HPP1 included a CpG island containing 49 CpG sites, of which 96% were found to be methylated by bisulfite sequencing of DNA from colonic tumor samples. By COBRA analysis, methylation was detected in six of nine (66%) adenomas, 17 of 27 (63%) hyperplastic polyps, and 46 of 55 (84%) colorectal cancers. There was an inverse relationship between methylation level and mRNA expression in cancers (r = -0.67; P < 0.001), and 5-aza-2-deoxycytidine treatment restored HPP1 expression in two colorectal cancer cell lines. In situ hybridization of HPP1 indicated that expression occurs in epithelial and stromal elements in normal mucosa but is silenced in both cell types in early colonic neoplasia. HPP1 is predicted to encode a transmembrane protein containing follistatin and epidermal growth factor-like domains. Silencing of HPP1 by methylation may increase the probability of neoplastic transformation.

Amino Acid Sequence↗
PubMed2001

Features of colorectal cancers with high-level microsatellite instability occurring in familial and sporadic settings: parallel pathways of tumorigenesis.

High-level microsatellite instability (MSI-H) is demonstrated in 10 to 15% of sporadic colorectal cancers and in most cancers presenting in the inherited condition hereditary nonpolyposis colorectal cancer (HNPCC). Distinction between these categories of MSI-H cancer is of clinical importance and the aim of this study was to assess clinical, pathological, and molecular features that might be discriminatory. One hundred and twelve MSI-H colorectal cancers from families fulfilling the Bethesda criteria were compared with 57 sporadic MSI-H colorectal cancers. HNPCC cancers presented at a lower age (P < 0.001) with no sporadic MSI-H cancer being diagnosed before the age of 57 years. MSI was less extensive in HNPCC cancers with 72% microsatellite markers showing band shifts compared with 87% in sporadic tumors (P < 0.001). Absent immunostaining for hMSH2 was only found in HNPCC tumors. Methylation of hMLH1 was observed in 87% of sporadic cancers but also in 55% of HNPCC tumors that showed loss of expression of hMLH1 (P = 0.02). HNPCC cancers were more frequently characterized by aberrant beta-catenin immunostaining as evidenced by nuclear positivity (P < 0.001). Aberrant p53 immunostaining was infrequent in both groups. There were no differences with respect to 5q loss of heterozygosity or codon 12 K-ras mutation, which were infrequent in both groups. Sporadic MSI-H cancers were more frequently heterogeneous (P < 0.001), poorly differentiated (P = 0.02), mucinous (P = 0.02), and proximally located (P = 0.04) than HNPCC tumors. In sporadic MSI-H cancers, contiguous adenomas were likely to be serrated whereas traditional adenomas were dominant in HNPCC. Lymphocytic infiltration was more pronounced in HNPCC but the results did not reach statistical significance. Overall, HNPCC cancers were more like common colorectal cancer in terms of morphology and expression of beta-catenin whereas sporadic MSI-H cancers displayed features consistent with a different morphogenesis. No individual feature was discriminatory for all HNPCC cancers. However, a model based on four features was able to classify 94.5% of tumors as sporadic or HNPCC. The finding of multiple differences between sporadic and familial MSI-H colorectal cancer with respect to both genotype and phenotype is consistent with tumorigenesis through parallel evolutionary pathways and emphasizes the importance of studying the two groups separately.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Effects elicited by toxaphene in the cynomolgus monkey (Macaca fascicularis): a pilot study.

Toxaphene, which was added to glycerol/corn oil, was administered at a level of 1 mg/kg body weight/day in gelatin capsules to four healthy young adult cynomolgus (Macaca fascicularis) monkeys for 52 weeks. Four control monkeys ingested capsules containing only glycerol/corn oil. Each group had two males and two females. On a daily basis, each monkey's feed and water consumption was determined, its health was monitored and the females were swabbed to evaluate menstrual status. On a weekly basis, each monkey's body weight was determined and a detailed clinical evaluation was performed. At 4-week intervals, blood samples were taken for serum biochemistry, haematology and toxaphene analysis. Also, a local anaesthetic was administered to the nuchal fat pad area of each monkey, and adipose samples were obtained for toxaphene analysis. 1 day prior to the biopsies, a 24-h urine and faecal collection was obtained for toxaphene analysis. After 34 weeks of treatment, the immune system of the monkeys was evaluated. After 52 weeks of dosing, all treated and two control animals were necropsied. Liver samples were obtained and microsomal fractions were prepared immediately. A portion of liver and kidney was taken for toxaphene analysis. All of the major internal organs were weighed and bone marrow evaluations were conducted. Organ and tissue samples were fixed in 10% formalin and processed for light microscopy. There was no effect of treatment on body weight gain, feed consumption, water consumption or haematological parameters. Two major clinical findings were inflammation and/or enlargement of the tarsal gland and impacted diverticulae in the upper and lower eye lids. At necropsy, the relative spleen and thymus weights were greater for the treated monkeys than the controls. Toxaphene administration produced an increase in metabolism of aminopyrene, methoxyresorufin and ethoxyresorufin, three substrates that are altered specifically by cytochrome P450-based hepatic monooxygenase enzymes. Histopathological examination of tissues was unremarkable by light microscopy. Tissue analysis for toxaphene and immunology findings have been published elsewhere.

Administration, Oral↗
PubMed2000

Behaviour, body composition and diet in adolescent girls.

The purpose of the study was to examine the relationships between patterns of behaviour, body composition and diet in adolescent girls. A group of 328 14 to 16-year-old girls at school in Southampton, U. K. completed a questionnaire about their behaviour and lifestyle, and had their heights, weights and skinfold thicknesses measured. Of these girls, 286 also provided dietary information. Socially independent girls were more likely to smoke, and less likely to eat breakfast and meals with family. They consumed more snacks, chocolate and soft drinks. Girls who were dissatisfied with their weight dieted and exercised, watched less television and spent less of their money on food. Dissatisfaction with weight was strongly related to body mass index. The odds of being a dieter, an indication of dissatisfaction with weight, increased with every unit increase in body mass index, so that girls with a body mass index of 24 kg/m(2)and over were 19 times more likely to diet than those with a body mass index of 19 kg/m(2)or less. Girls who were less satisfied with their weight reported lower energy intakes but ate more green vegetables and brown bread than other girls. The eating habits of the girls were therefore influenced by the extent of their social lives and by their satisfaction with their weight.

Adolescent↗
PubMed2000

Integration of advanced process control and full-scale dynamic simulation

In the process control industry, multivariable model predictive controller and dynamic simulation for operator training are usually available in separate packages. It is very difficult for the operators and plant engineers to find good tools for them to get trained in multivariable advanced process control. This paper presents a system, which integrates the advanced process control and full-scale dynamic simulation. The advanced process control uses multivariable model predictive control techniques. The model used in the predictive control algorithms is generated from the dynamic simulated process. The advanced process controller can control the simulated plant directly, or through a DCS system to control the simulated plant. The combined system provides an excellent environment for training operators in process operation with multivariable advanced process control. The same environment is also very useful for engineers in designing and tuning the advanced process controllers, and in testing communication between the advanced process controller and the DCS systems, or the other type of process control systems.

Journal Article↗
PubMed2000

Prognostic significance of extensive microsatellite instability in sporadic clinicopathological stage C colorectal cancer.

BACKGROUND: Colorectal cancers exhibiting microsatellite instability (MSI) appear to have unique biological behaviour. This study analyses the association between extensive MSI (MSI-H), clinicopathological features and survival in an unselected group of patients with sporadic Australian Clinico-Pathological Stage (ACPS) C (tumour node metastasis stage III) colorectal cancer. METHODS: Some 255 patients who underwent resection for sporadic ACPS C colorectal cancer between 1986 and 1992 were studied. No patient had received chemotherapy. Minimum follow-up for all patients was 5 years. Archival normal and tumour DNA was extracted and amplified by polymerase chain reaction using a radioactive labelling technique. MSI-H was defined as instability in 40 per cent or more of seven markers. RESULTS: Twenty-one patients showed MSI-H. No association was found between MSI and age or sex. Tumours exhibiting MSI-H were more commonly right sided (P<0.00001), larger (P = 0.002) and more likely to be high grade (P = 0.049). After adjustment for age, sex and other pathological variables, patients whose cancers exhibited MSI-H had improved survival (P = 0.015). CONCLUSION: Recognition of MSI-H in sporadic ACPS C tumours identifies a subset of cancers with improved prognosis. Such stratification should be considered in trials of adjuvant therapy and may be relevant to therapeutic decision making.

Adult↗
PubMed2000

Meningococcal C polysaccharide vaccine induces immunologic hyporesponsiveness in adults that is overcome by meningococcal C conjugate vaccine.

Widespread use of meningococcal AC polysaccharide (MACP) vaccines has raised concerns about induction of hyporesponsiveness to C polysaccharide. Whether meningococcal C conjugate (MCC) vaccine overcomes any immunologic refractoriness following MACP vaccination in adults was investigated. University students vaccinated 6 months previously with MACP vaccine were randomized to receive MACP or MCC vaccine, and antibody responses were compared with those of previously unvaccinated students receiving MACP or MCC vaccine. In students primed with MACP vaccine, MCC vaccine induced significantly higher IgG and serum bactericidal antibody levels than did a second dose of MACP vaccine. Responses to a second dose of MACP vaccine were significantly lower than to the first dose. Previous receipt of MACP vaccine reduced serum bactericidal antibody but not IgG responses to MCC vaccine compared with those in previously unvaccinated students. This confirms that MACP vaccine induces immunologic hyporesponsiveness to C polysaccharide in adults, but this can be overcome with MCC vaccine. Repeated vaccination with MACP vaccine may be ineffective, and MCC vaccines should provide better long-term protection.

Adolescent↗
PubMed2000

The role of technical assistance in the replication of effective HIV interventions.

This article examines the role of technical assistance (TA) in supporting the replication of proven HIV interventions. A case study of the replication of the VOICES/VOCES intervention elucidates the level and types of TA provided to support new users through the adoption process. TA included help in garnering administrative support, identifying target audiences, recruiting groups for sessions, maintaining fidelity to the intervention's core elements, tailoring the intervention to meet clients' needs, strengthening staff members' facilitation skills, troubleshooting challenges, and devising strategies to sustain the intervention. Two to four hours per month of TA were provided to each agency adopting the intervention, at an estimated monthly cost of $206 to $412. Findings illustrate how TA supports replication by establishing a conversation between the researcher TA providers experienced with the intervention and new users. This communication helps preserve key program elements and contributes to ongoing refinement of the intervention.

Community Health Services↗
PubMed1999

Effects of hyperoxia on oxygen uptake kinetics in cystic fibrosis patients as determined by pseudo-random binary sequence exercise.

Patients with cystic fibrosis (CF) have been shown to exhibit impaired oxygen uptake (VO2) kinetics independent of their physical fitness. This study investigated whether oxygen supplementation improves VO2 kinetics in CF as determined by cycle ergometry at submaximal exercise intensities using a pseudo-random binary sequence exercise test i.e. a simultaneous application of different frequencies of sinusoidal work. The subjects were 9 CF patients and 13 healthy controls (HC) and they exercised while breathing humidified and heated air with a fractional concentration of oxygen in inspired air (F(I)O2) of either 0.21 or 0.40. With a F(I)O2 of 0.21 the respiratory exchange ratio (R) was higher in CF than in HC both at rest (0.91 vs 0.81) and during exercise (0.97 vs 0.89). Oxygen saturation (SO2) was slightly lower in CF. but remained above 90% during exercise (92.7% vs 95.2%). Spectrum analysis revealed that in CF, the amplitude ratio (AR) between V02 and exercise intensity was lower over a wide frequency range (P < 0.05). In addition, CF showed a larger negative phase shift (PS) at lower frequencies (P < 0.005). With a F(I)O2 of 0.40, SO2 increased to about 97% in both groups; while R remained higher in CF (0.92) compared to HC (0.81). In the control group, the O2 supplement raised AR but the VO, kinetics of the CF patients were not significantly affected. In HC the enhanced AR during oxygen supplementation would suggest a cardiopulmonary limitation of VO2 at the onset of submaximal exercise. In CF patients low AR and PS would indicate an attenuated VO2 response attributable to an impaired oxygen utilization in the muscles because the oxygen supplement normalised SO2 but failed to improve R and VO2 kinetics.

Adolescent↗
PubMed1999

Meningococcal disease at the University of Southampton: outbreak investigation.

In October 1997, an outbreak of meningococcal disease occurred at the University of Southampton. All six cases were first year students living in halls of residence. Microbiological characterization of case and carrier strains, case interviews, and a meningococcal carriage prevalence survey were used to investigate the outbreak. Five cases were due to serogroup C strains, one case was unconfirmed. Serotyping did not distinguish between the strains but gene sequencing permitted identification of two distinct strains in the outbreak. Although none of the cases was known to each other, three had attended the same nightclub one evening 3-4 days before illness. Meningococcal carriage rates in undergraduates were within the range expected (147/587, 25%), but no carriers of outbreak strains were identified in this sample. The findings suggest that in communities with a high degree of social interaction, the introduction of highly virulent meningococcal strains may result in enhanced transmission with clustering of cases.

Adolescent↗
PubMed1999

Assessing the diet of adolescent girls in the UK.

OBJECTIVE: To assess the ability of a food frequency questionnaire (FFQ1) and a food checklist (FCL) to determine energy and macronutrient intakes of adolescent girls in the general population. DESIGN: Energy and macronutrient intakes determined by FFQ1 and the FCL were compared with those from a 7-day weighed dietary record (WDR). The reproducibility of FFQ1 was assessed by a comparison of intakes with those from a repeated questionnaire (FFQ2) completed a month later. SETTING: Southampton, UK. SUBJECTS: Forty-seven 15-year-old girls completed FFQ1 and the WDR and FCL; and 61 girls completed FFQ1 and FFQ2. RESULTS: The broad dietary patterns described by the three methods of assessment were similar, although absolute intakes differed. Energy and macronutrient intakes determined by FFQ1 were higher than those recorded in the WDR (all P < 0.001), but intakes assessed by the FCL and WDR were similar. Only FFQ1-assessed energy intakes appeared consistent with predicted energy requirements. With the exception of protein intake, there was reasonable agreement between FFQ1 and the WDR in their estimation of energy and macronutrient intake (range of correlation coefficients 0.28 for energy to 0.33 for carbohydrate). The poorer agreement between FFQ1 and the WDR in their estimates of protein intake arose principally from the misclassification of meat and fish intake, although there was no obvious explanation for this. Energy and macronutrient intakes were similar for FFQ1 and FFQ2. CONCLUSIONS: Adolescent girls give reproducible answers in response to a self-administered FFQ, which yield useful information about their broad dietary patterns. The FFQ may be a more suitable dietary assessment method than prospective records for use in general population studies of girls of this age. We discuss suggestions for its improved performance.

Adolescent↗
PubMed1999

Adenovirus infections in hematopoietic stem cell transplant recipients.

We report a 12% incidence of adenovirus infections among 532 recipients of hematopoietic stem cell transplant (HSCT) from January 1986 through March 1997. The median time from day of stem cell infusion to first positive culture was 41 days. Recipients of allogeneic stem cells, as opposed to autologous stem cell recipients, were more likely to have a culture positive for adenovirus (16% vs. 3%; P<.0001). Pediatric patients were also more likely than adults to have a positive culture (23% vs. 9%; P<.0001). Among stem cell recipients with partially matched related donors, pediatric recipients appear to be at significantly greater risk for infection than adult recipients (P<.001). Positive cultures were associated with evidence of invasion in 64% of cases (41 of 64). A multiple logistic regression analysis showed that isolating adenovirus from more than 1 site correlated with greater risk for invasive infections (P=.002). Invasive infections were associated with poorer chance of survival.

Adenovirus Infections, Human↗
PubMed1999

The effect of long-term deafness on speech recognition in postlingually deafened adult CLARION cochlear implant users.

Research suggests that duration of deafness prior to cochlear implantation affects postoperative speech recognition in adults. Duration of deafness usually is defined as the number of years between the onset of profound deafness and implantation. The purpose of this study was to examine the effects of duration of deafness--expressed as percentage of life with deafness--independent of age at implantation on postoperative speech recognition in adult postlingually deafened CLARION Multi-Strategy Cochlear Implant users. Speech recognition tests (CID sentences and NU6 words) were administered to 202 consecutively implanted adults preoperatively and at 3 and 6 months after initial device fitting. Patients implanted at a younger age and those with smaller percentages of their lives with deafness achieved the highest levels of short-term postoperative speech recognition. Patients who had been deaf for > or =60% of their lives demonstrated a slower rate of speech recognition improvement than those with shorter durations of deafness, but still continued to improve with increased implant experience.

Adult↗
PubMed1999

Clinical trial of the CLARION cochlear implant in children.

Preoperative and postoperative efficacy results are reported for the first 58 children with 18 months of implant experience in the United States. A within-subjects repeated-measures design was used to compare preoperative performance with hearing aids to postoperative performance with the CLARION Multi-Strategy Cochlear Implant. The results revealed significant improvement over time on all speech perception measures. Higher scores and faster rates of progress were demonstrated by the children who used oral communication compared to children who used total communication, especially older children. The overall results suggest higher levels of performance and more rapid progress in the development of listening skills than has been reported in previous clinical trials with children. The latter finding appears to be due to advances in implant technology and changes in the demographic characteristics of the study groups.

Child↗