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Biomedical subjects

D Thompson

Publications and source records attributed to D Thompson.

At least 19 recordsLinked to original sources
PubMed2006

Cost-effectiveness of screening with contrast enhanced magnetic resonance imaging vs X-ray mammography of women at a high familial risk of breast cancer.

Contrast enhanced magnetic resonance imaging (CE MRI) is the most sensitive tool for screening women who are at high familial risk of breast cancer. Our aim in this study was to assess the cost-effectiveness of X-ray mammography (XRM), CE MRI or both strategies combined. In total, 649 women were enrolled in the MARIBS study and screened with both CE MRI and mammography resulting in 1881 screens and 1-7 individual annual screening events. Women aged 35-49 years at high risk of breast cancer, either because they have a strong family history of breast cancer or are tested carriers of a BRCA1, BRCA2 or TP53 mutation or are at a 50% risk of having inherited such a mutation, were recruited from 22 centres and offered annual MRI and XRM for between 2 and 7 years. Information on the number and type of further investigations was collected and specifically calculated unit costs were used to calculate the incremental cost per cancer detected. The numbers of cancer detected was 13 for mammography, 27 for CE MRI and 33 for mammography and CE MRI combined. In the subgroup of BRCA1 (BRCA2) mutation carriers or of women having a first degree relative with a mutation in BRCA1 (BRCA2) corresponding numbers were 3 (6), 12 (7) and 12 (11), respectively. For all women, the incremental cost per cancer detected with CE MRI and mammography combined was pound28 284 compared to mammography. When only BRCA1 or the BRCA2 groups were considered, this cost would be reduced to pound11 731 (CE MRI vs mammography) and pound15 302 (CE MRI and mammography vs mammography). Results were most sensitive to the unit cost estimate for a CE MRI screening test. Contrast-enhanced MRI might be a cost-effective screening modality for women at high risk, particularly for the BRCA1 and BRCA2 subgroups. Further work is needed to assess the impact of screening on mortality and health-related quality of life.

Adult↗
PubMed2006

Modeling competitive guest binding to beta-cyclodextrin molecular printboards.

Anchoring of functionalized guest molecules to self-assembled monolayers (SAMs) is key to the development of molecular printboards for nanopatterning. One very promising system involves guest binding to immobilized beta-cyclodextrin (beta-CD) hosts, with guest:host recognition facilitated by a hydrophobic interaction between uncharged anchor groups on the guest molecule and beta-CD hosts self-assembled at gold surfaces. We use molecular dynamics free energy (MDFE) simulations to describe the specificity of guest:beta-CD association. We find good agreement with experimental thermodynamic measurements for binding enthalpy differences between three commonly used phenyl guests: benzene, toluene, and t-butylbenzene. van der Waals interaction with the inside of the host cavity accounts for almost all of the net stabilization of the larger phenyl guests in beta-CD. Partial and full methylation of the secondary rim of beta-CD decreases host rigidity and significantly impairs binding of both phenyl and larger adamantane guest molecules. The beta-CD cavity is also very intolerant of guest charging, penalizing the oxidized state of ferrocene by at least 7 kcal/mol. beta-CD hence expresses moderate specificity toward uncharged organic guest molecules by van der Waals recognition, with a much higher specificity calculated for electrostatic recognition of organometallic guests.

Journal Article↗
PubMed2006

A prospective study of neurofibromatosis type 1 cancer incidence in the UK.

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition affecting around one in 3000 live births. The manifestations of this condition are extremely variable, even within families, and genetic counselling is consequently difficult with regard to prognosis. Individuals with NF1 are acknowledged to be at increased risk of malignancy. Several studies have previously attempted to quantify this risk, but have involved relatively small study populations. We present prospective data from 448 individuals with NF1 with a total of 5705 years of patient follow-up. These data have been collected via the UK NF1 association for patients. Demographic information on the affected individuals was cross-referenced with UK cancer registry data by the UK Office of National Statistics. The overall risk of cancer was 2.7 times higher in this cohort of NF1 patients than in the general population (95% confidence interval (CI) 1.9-3.7). The cumulative risk of a malignancy by age 50 years was 20% (95% CI 14-29%); beyond this age, the risk of cancer was not significantly elevated (P=0.27). The most frequent types of cancer were connective tissue (14% risk by age 70, 95% CI 7.8-24%) and brain tumours (7.9, 95% CI 3.9-16%). There was no statistically significant excess of cancers at other sites (P=0.22).

Adolescent↗
PubMed2006

Supraesophageal reflux: validation of a symptom questionnaire.

OBJECTIVE: To develop and validate a questionnaire for supraesophageal manifestations of reflux (SER) that will facilitate its study in clinical and research settings. STUDY DESIGN: The Supraesophageal Reflux Questionnaire (SERQ) and previously validated Reflux Symptom Index (RSI) were subjected to multiple types of validity testing, including content validity, concurrent validity, reproducibility, and predictive validity. RESULTS: The concurrent validity and reproducibility of both instruments was good to excellent for most items tested. The predictive validity of the SERQ was superior to the RSI when it included the covariates of history of sinusitis, use of over-the-counter antacid medications, age, gender, and body mass index. CONCLUSIONS: The SERQ will serve as both a useful clinical and research tool by offering not only SER symptom information, like the RSI, but also information about the patient's medical history and medication usage that will facilitate use of the SERQ in research protocols. EBM RATING: B-2b.

Antacids↗
PubMed2005

Ischaemic skeletal muscle increases serum ischaemia modified albumin.

OBJECTIVES: Ischaemia modified albumin (IMA) has been used as a marker of myocardial ischaemia but little is known about its production during ischaemia of other tissues. The clinical models of patients with intermittent claudication and major arterial surgery were used to investigate IMA production from ischaemic skeletal muscle. DESIGN: Prospective clinical study. MATERIALS AND METHODS: IMA was measured pre-operatively, at end ischaemia, and 5 min, 4, 24, 48, 72 and 144 h post-surgery in patients undergoing (a) revascularisation for intermittent claudication (IC, n=15), (b) abdominal aortic aneurysm repair (AAA, n=12) and controls (n=16). RESULTS: The median pre-operative IMA concentration in IC patients was significantly higher than the AAA group (88.3 versus 83.5 U/ml, p=0.036) and controls (88.3 versus 80.3 U/ml, p=0.031). IMA concentrations increased significantly during arterial clamping in both IC and AAA groups (88.3 versus 120.0 U/ml, p=0.001; 83.5 versus 118.8 U/ml, p=0.002, respectively) consistent with increased skeletal muscle ischaemia. In contrast, there was only a mild perioperative increase in the controls (80.3 versus 91.6 U/ml, p=0.012). CONCLUSIONS: Patients with intermittent claudication have significantly elevated IMA and skeletal muscle ischaemia during arterial surgery results in significantly increased circulating IMA. When IMA is used to detect myocardial ischaemia, ischaemic skeletal muscle must be excluded.

Adult↗
PubMed2005

BMI from 3-6 y of age is predicted by TV viewing and physical activity, not diet.

OBJECTIVE: To investigate whether, diet, physical activity, sedentary behavior or television (TV) viewing predicted body mass index (BMI) among 3-7-y-old children. DESIGN: A triethnic cohort of 3-4-y-old children was followed for 3 y from 1986 to 1989. MEASUREMENTS: BMI was assessed at the beginning and end of each measurement year. Heart rate monitoring and observation were used to assess physical activity. Diet (calories, % calories from fat and carbohydrate), sedentary behavior and TV viewing were assessed by direct observation in each year. A repeated measures regression analysis with year as a factor and BMI at the end of each year as dependent variables was run. Nonsignificant variables were removed in a stepwise backward deletion process and significant interactions graphed. RESULTS: The interactions between minutes of TV viewing per hour and study year and minutes of physical activity per hour and study year were significant (P<0.05). There were also significant main effects for TV viewing, physical activity and BMI from the beginning of the study. The model accounted for 65% of the variance in BMI across the three study years. Plotting the significant interactions demonstrated that physical activity was positively associated with BMI in year 1, and negatively associated in years 2 and 3 with a stronger negative relationship in year 3 than 2. TV viewing became positively associated with BMI during the third study year. CONCLUSION: Physical activity and TV viewing were the only significant predictors (other than baseline BMI) of BMI among a triethnic cohort of 3-4-y-old children followed for 3 y with both physical activity (negatively associated) and TV viewing (positively associated) becoming stronger predictors as the children aged. It appears that 6 or 7 y is a critical age when TV viewing and physical activity may affect BMI. Therefore, focusing on reducing time spent watching television and increasing time spent in physical activity may be successful means of preventing obesity among this age group.

Activities of Daily Living↗
PubMed2005

Localized versus regional hyperthermia: comparison of xenotransplants treated with a small animal ultrasound system and waterbath limb immersion.

The response of xenotransplants were compared with waterbath immersion vs focal ultrasound (US) hyperthermia using tumour growth delay, immunhistochemistry and histopathology assays. Waterbath hyperthermia was performed by limb immersion. Precautions were taken to minimize total body heating by surrounding the mouse with plastic insulators. Thermometry was performed with clinical-grade, 20-gauge needle thermocouples and monitored with a Labthermics unit. Significant differences in cytotoxicity between ultrasound and waterbath treatment of tumors at 43 degrees C were observed as determined by TUNNEL assay. Conversely, contralateral (non-treated) tumours in animals treated with similar temperature demonstrated no significant differences between modalities. Western blot analysis revealed increased hsp70 induction at 43 degrees C in waterbath vs focal ultrasound hyperthermia. Comparison of tumour growth delay between tumours heated with waterbath vs ultrasound at 43 degrees C but not at 41 degrees C revealed significant differences. This is the first study comparing localized vs regional hyperthermia using the small animal ultrasound system (SAHUS) delivery system. Consistent ultrasound hyperthermia can be achieved throughout a xenotransplant. At equivalent temperature of 43 degrees C for 60?min, waterbath hyperthermia demonstrated greater local response vs ultrasound hyperthermia.

Animals↗
PubMed2005

HFE genotype modifies the influence of heme iron intake on iron status.

BACKGROUND: Public health policy to prevent iron deficiency through food fortification or other measures may be disadvantageous to people with hereditary hemochromatosis. METHODS: From a cohort of U.K. women, 2531 women were typed for C282Y and H63D mutations in the hemochromatosis gene. These women completed food frequency questionnaires and provided blood for iron status. RESULTS: C282Y homozygotes (n=31) had serum ferritin concentrations 2.4 times higher (95% confidence interval=1.9-3.1) than wild types (n=1774), but heterozygotes (n=726) were not different from wild types. H63D genotype had no effect on its own. The effect of heme iron intake (from meat, fish, and poultry) was 2.0 times greater (1.2-3.2) on C282Y homozygotes than other groups. Nonheme iron had little effect. CONCLUSIONS: There may be scope for dietary intervention in women homozygous for the C282Y mutation. C282Y heterozygotes and H63D homozygotes and heterozygotes have similar serum ferritin concentrations to wild type and need not reduce their meat intake other than as part of a normal healthy diet.

Adult↗
PubMed2005

Factors associated with bicycle helmet use among young adolescents in a multinational sample.

OBJECTIVE: To determine factors associated with variation in bicycle helmet use by youth of different industrialized countries. DESIGN: A multinational cross sectional nationally representative survey of health behaviors including symptoms, risk taking, school setting, and family context. SETTING: School based survey of 26 countries. SUBJECTS: School students, ages 11, 13, and 15 years totaling 112,843. OUTCOME MEASURES: Reported frequency of bicycle helmet use among bicycle riders. RESULTS: Reported helmet use varied greatly by country from 39.2% to 1.9%, with 12 countries reporting less than 10% of the bicycle riders as frequent helmet users and 14 countries more than 10%. Reported helmet use was highest at 11 years and decreased as children's age increased. Use was positively associated with other healthy behaviors, with parental involvement, and with per capita gross domestic product of the country. It is negatively associated with risk taking behaviors. Countries reported to have interventions promoting helmet use, exemplified by helmet giveaway programmes, had greater frequency of reported helmet use than those without programmes. CONCLUSIONS: Bicycle helmet use among young adolescents varies greatly between countries; however, helmet use does not reach 50% in any country. Age is the most significant individual factor associated with helmet for helmet using countries. The observation that some helmet promotion programmes are reported for countries with relatively higher student helmet use and no programmes reported for the lowest helmet use countries, suggests the possibility of a relation and the need for objective evaluation of programme effectiveness.

Adolescent↗
PubMed2005

Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies.

A recent report estimated the breast cancer risks in carriers of the three Ashkenazi founder mutations to be higher than previously published estimates derived from population based studies. In an attempt to confirm this, the breast and ovarian cancer risks associated with the three Ashkenazi founder mutations were estimated using families included in a previous meta-analysis of populatrion based studies. The estimated breast cancer risks for each of the founder BRCA1 and BRCA2 mutations were similar to the corresponding estimates based on all BRCA1 or BRCA2 mutations in the meta-analysis. These estimates appear to be consistent with the observed prevalence of the mutations in the Ashkenazi Jewish population.

Adult↗
PubMed2005

Transforming the tobacco market: why the supply of cigarettes should be transferred from for-profit corporations to non-profit enterprises with a public health mandate.

Current tobacco control strategies seek primarily to decrease the demand for cigarettes through measures that encourage individuals to adopt healthier behaviours. These measures are impeded and undermined by tobacco corporations, whose profit drive compels them to seek to maintain and expand cigarette sales. Tobacco corporations seek to expand cigarette sales because they are for-profit business corporations and are obliged under law to maximise profits, even when this results in harm to others. It is not legally possible for a for-profit corporation to relinquish its responsibility to make profits or for it to temper this obligation with responsibilities to support health. Tobacco could be supplied through other non-profit enterprises. The elimination of profit driven behaviour from the supply of tobacco would enhance the ability of public health authorities to reduce tobacco use. Future tobacco control strategies can seek to transform the tobacco market from one occupied by for-profit corporations to one where tobacco is supplied by institutions that share a health mandate and will help to reduce smoking and smoking related disease and death.

Commerce↗
PubMed2004

Prolonged vitamin C supplementation and recovery from eccentric exercise.

We have previously shown that vitamin C supplementation affects recovery from an unaccustomed bout of demanding exercise, with the most pronounced effect being that on plasma interleukin-6 concentration. However, because of the proposed role of interleukin-6 in the regulation of metabolism, it was unclear whether this represented a reduced response to muscle damage or some form of interaction with the metabolic demands of the activity. Therefore, the aim of the present study was to investigate the effect of the same form of supplementation on a bout of exercise that initiated similar muscle damage but had a low metabolic cost. Fourteen male subjects were allocated to either a placebo (P) or a vitamin C (VC) group. The VC group consumed 200 mg of ascorbic acid twice a day for 14 days prior to a bout of exercise and for the 3 days after exercise. The P group consumed identical capsules that contained 200 mg lactose. Subjects performed 30 min of downhill running at a gradient of -18% and recovery was monitored for up to 3 days after exercise. Plasma VC concentrations in the VC group increased following supplementation. Nevertheless, downhill running provoked a similar increase in circulating markers of muscle damage (creatine kinase activity and myoglobin concentration) and muscle soreness in P and VC groups. Similarly, although downhill running increased plasma interleukin-6, there was no effect from VC supplementation. These results suggest that vitamin C supplementation does not affect interleukin-6 concentrations following eccentric exercise that has a low metabolic component.

Adult↗
PubMed2004

Hypertension as a marker for later development of end-stage renal failure after lung and heart-lung transplantation: a cohort study.

BACKGROUND: Time to renal failure after transplantation is not well known and the prognosis of lung and heart-lung transplantation with respect to end-stage renal failure and related factors has not been investigated in detail. We determined the predictors of end-stage renal failure after lung or heart-lung transplant using multivariate analysis. METHODS: A cohort study of 115 adult patients transplanted between 1990 and 1995, who survived at least 5 years, was carried out. Characteristics and clinical findings, including blood pressure, creatinine clearance and immunosuppression levels of patients with end-stage renal failure, were compared with those without, initially in a univariate analysis. Then a multivariate logistic regression model was built to examine the association of predictor variables with end-stage renal failure after adjustment for confounding. RESULTS: There were 19 of 115 (16.4%) patients with end-stage renal failure, with an average time of loss of renal function of 7.6 years (95% confidence interval [CI] 6.5 to 8.7) after transplantation. There was no difference in survival between patients with end-stage renal failure and those without. Multivariate analysis showed that development of hypertension post-operatively was the only significant predictor variable (odds ratio 8.16, 95% CI 1.01 to 66.0, p = 0.04). Patients' age at transplantation, gender, underlying medical conditions and other post-transplant features were not associated with end-stage renal failure. CONCLUSIONS: Development of hypertension after lung or heart-lung transplant should be used a marker for later development of end-stage renal failure. Any hypertension should be treated energetically. Acute renal failure immediately post-operatively did not predict end-stage renal failure in this cohort of patients.

Adult↗
PubMed2004

Systematic review of interventions to reduce delay in patients with suspected heart attack.

OBJECTIVES: To evaluate the effectiveness of interventions aiming to reduce time from onset of signs and symptoms of an acute myocardial infarction (AMI) to seeking medical help/arrival at hospital. METHODS: A systematic review was conducted. Fifteen electronic databases, the internet, and bibliographies of included studies were searched, and experts in the field of cardiac care were contacted. Randomised controlled trials (RCTs), controlled trials, and before and after studies conducted in any setting that assessed an intervention aimed at reducing time from onset of signs and symptoms of an AMI to seeking medical help and/or arrival in hospital were eligible for inclusion. RESULTS: Eleven media/public education intervention studies met the inclusion criteria. Five (one controlled and four before and after studies) reported the intervention to have a statistically positive effect on delay time and six (two RCTs and four before and after studies) reported no statistically significant effect. Three (one RCT and two before and after studies) of five studies evaluating the effect of the intervention on emergency department visits reported an increase in this outcome as a result of the intervention, and both studies (one RCT and one before and after study) examining calls made to emergency switchboards reported an increase in this outcome after the intervention. CONCLUSIONS: There was little evidence that media/public education interventions reduced delay. There is some evidence that they may result in an increase in emergency switchboard calls and emergency department visits. Despite substantial expenditure of time and effort, methodological deficiencies of the studies mean that it is not possible to make definitive recommendations.

Health Education↗
PubMed2004

Evidence for interaction between the TCO and NMTC1 loci in familial non-medullary thyroid cancer.

BACKGROUND: Familial non-medullary thyroid cancer (fNMTC) is a complex genetic disorder that is more aggressive than its sporadic counterpart. Thus far, three genetic loci have been implicated in susceptibility to fNMTC by linkage analysis. METHODS: We used linkage analysis to test the significance of two of the known susceptibility loci for fNMTC, TCO on 19p13 and NMTC1 on 2q21 in 10 fNMTC families, nine of which present with cell oxyphilia, a rare histological phenotype associated with TCO. Furthermore, we used two-locus linkage analysis to examine the possibility that the TCO and NMTC1 loci interact to increase the risk of NMTC. RESULTS: The 10 families provided evidence for linkage at both TCO and NMTC, with LOD scores of 1.56 and 2.85, respectively. Two-locus linkage analysis, using a multiplicative risk model for the development of NMTC, achieved a maximum LOD of 3.92, with an LOD of 4.51 when assuming 70% of families were linked, indicating that the segregation in these families is consistent with an interaction model. Most of this evidence came from a large Tyrolean family that singularly achieved a two-locus LOD of 3.21. CONCLUSIONS: These results provide further evidence that susceptibility genes for fNMTC exist at 19p13 and 2q21, and furthermore, raise the possibility that in a subset of fNMTC pedigrees, these loci interact resulting in significantly increased risk of NMTC for patients that carry both susceptibility loci.

Adenoma, Oxyphilic↗
PubMed2004

Differences in demographics and risk factors among men attending public v non-public STD clinics in Baltimore, Maryland.

OBJECTIVE: To compare the demographics and risk factors of men who utilise the services of a municipal public sexually transmitted disease (STD) clinic with those who utilise the services provided by a non-public men's STD clinic operated by a not for profit primary care clinic. METHODS: A record based review of the characteristics and STD prevalence of men who visited a non-public STD clinic in Baltimore, Maryland, compared with those of a random sample of male attendees of a public STD clinic. Data abstracted from the records included information on age, race/ethnicity, self reported risk behaviours, and STD tests and results. We used chi2 analysis as well as bivariate and multivariate modelling to compare differences in categorical factors between clinics groups. RESULTS: Men who utilised the services at the non-public STD clinic were more often white (71% v 3%, p<0.001), MSM (65% v 2%, p<0.001), and presented for general screening (52% v 15%, p<0.001) compared to those at the public clinic. In addition, they more frequently reported > or =3 partners (22% v 11%, p=0.005), and having an HIV positive partner (10% v 3%, p=0.005). Factors independently associated with attendance at non-public clinic in multivariate analysis were general screening as reason for visit (OR = 11.0, p<0.001), having 3+ partners in past month (OR=10.5, p=0.002), and "sometimes" using condoms (OR=3.6, p=0.033). CONCLUSIONS: Non-public STD clinics can reach a distinct segment of the male population with high risk sexual behaviours that might not attend public STD clinics.

Adult↗
PubMed2004

Cloning and characterization of an inversion breakpoint at 6q23.3 suggests a role for Map7 in sacral dysgenesis.

Here we report on a male patient with sacral dysgenesis (SD) and constitutional pericentric inversion of chromosome 6 (p11.2;q23.3). SD is a heterogeneous group of congenital anomalies with complex genetic etiology. Previously, a patient with sacral abnormalities and an interstitial deletion of 6q23-->q25 region has been described. We speculated that a susceptibility gene for SD lies in 6q23.3 region (disrupted in both patients), and therefore, cloning of the breakpoint in our patient would lead to the identification of the disrupted gene. We performed FISH analysis followed by Southern blot analysis and inverse PCR to clone the breakpoint. The 6p11.2 breakpoint mapped very close to the centromere, and the 6q23.3 breakpoint localized in the ninth intron of the MAP7 gene. We then evaluated the involvement of MAP7 in SD by further screening of the gene in several patients with a similar phenotype. Two nucleotide changes causing Ile257Asn and Glu571Ala substitutions in the protein, both affecting amino acid residues conserved in the mouse homolog, were identified in two patients. Both changes are either very rare polymorphisms or true mutations, since they were not detected in 167 normal individuals nor found in the SNP database. Therefore, our study suggests MAP7 as a candidate gene for SD. However, we were unable to detect any sacral defects in the MAP7 knockout mice.

Abnormalities, Multiple↗