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D Thompson

Publications and source records attributed to D Thompson.

At least 55 records · Page 3Linked to original sources

Transcontinental communication and quantitative digital histopathology via the Internet; with special reference to prostate neoplasia.

OBJECTIVE: To describe practical experiences in the sharing of very large digital data bases of histopathological imagery via the Internet, by investigators working in Europe, North America, and South America. MATERIALS: Experiences derived from medium power (sampling density 2.4 pixels/microm) and high power (6 pixels/microm) imagery of prostatic tissues, skin shave biopsies, breast lesions, endometrial sections, and colonic lesions. Most of the data included in this paper were from prostate. In particular, 1168 histological images of normal prostate, high grade prostatic intraepithelial neoplasia (PIN), and prostate cancer (PCa) were recorded, archived in an image format developed at the Optical Sciences Center (OSC), University of Arizona, and transmitted to Ancona, Italy, as JPEG (joint photographic experts group) files. Images were downloaded for review using the Internet application FTP (file transfer protocol). The images were then sent from Ancona to other laboratories for additional histopathological review and quantitative analyses. They were viewed using Adobe Photoshop, Paint Shop Pro, and Imaging for Windows. For karyometric analysis full resolution imagery was used, whereas histometric analyses were carried out on JPEG imagery also. RESULTS: The three applications of the telecommunication system were remote histopathological assessment, remote data acquisition, and selection of material. Typical data volumes for each project ranged from 120 megabytes to one gigabyte, and transmission times were usually less than one hour. There were only negligible transmission errors, and no problem in efficient communication, although real time communication was an exception, because of the time zone differences. As far as the remote histopathological assessment of the prostate was concerned, agreement between the pathologist's electronic diagnosis and the diagnostic label applied to the images by the recording scientist was present in 96.6% of instances. When these images were forwarded to two pathologists, the level of concordance with the reviewing pathologist who originally downloaded the files from Tucson was as high as 97.2% and 98.0%. Initial results of studies made by researchers belonging to our group but located in others laboratories showed the feasibility of making quantitative analysis on the same images. CONCLUSIONS: These experiences show that diagnostic teleconsultation and quantitative image analyses via the Internet are not only feasible, but practical, and allow a close collaboration between researchers widely separated by geographical distance and analytical resources.

Computers↗

Economic costs of the foot and mouth disease outbreak in the United Kingdom in 2001.

The authors present estimates of the economic costs to agriculture and industries affected by tourism of the outbreak of foot and mouth disease (FMD) in the United Kingdom (UK) in 2001. The losses to agriculture and the food chain amount to about Pound Sterling3.1 billion. The majority of the costs to agriculture have been met by the Government through compensation for slaughter and disposal as well as clean-up costs. Nonetheless, agricultural producers will have suffered losses, estimated at Pound Sterling355 million, which represents about 20% of the estimated total income from farming in 2001. Based on data from surveys of tourism, businesses directly affected by tourist expenditure are estimated to have lost a similar total amount (between Pound Sterling2.7 and Pound Sterling3.2 billion) as a result of reduced numbers of people visiting the countryside. The industries which supply agriculture, the food industries and tourist-related businesses will also have suffered losses. However, the overall costs to the UK economy are substantially less than the sum of these components, as much of the expenditure by tourists was not lost, but merely displaced to other sectors of the economy. Overall, the net effect of FMD is estimated to have reduced the gross domestic product in the UK by less than 0.2% in 2001.

Agriculture↗

Genome-wide linkage disequilibrium mapping of late-onset Alzheimer's disease in Finland.

BACKGROUND: AD is a complex neurodegenerative disorder comprising several disease-associated chromosome loci. To find novel susceptibility genes for late-onset AD, a population-based genome-wide search using linkage disequilibrium (LD) mapping approach has been performed. METHOD: Forty-seven patients with late-onset AD and 51 age-matched control subjects were carefully chosen from the same geographic area in eastern Finland, where the population is descended mainly from a small group of original founders. These subjects were initially genotyped with 366 polymorphic microsatellite markers, and a follow-up analysis was performed with additional microsatellite markers for those chromosome loci found to be associated with AD. RESULTS: Initial genome-wide screening revealed 21 chromosomal loci significantly associated with AD in addition to the 13q12 locus described previously. Subsequent comparison of single-allele frequencies of the microsatellite markers in the AD and control groups indicated the presence both of possible risk alleles (odds ratio [OR] > 1) and of possible protective alleles (OR < 1). Screening of the LD regions with additional microsatellite markers revealed seven chromosomal loci where more than one microsatellite marker was associated with AD (1p36.12, 2p22.2, 3q28, 4p13, 10p13, 18q12.1, and 19p13.3) in addition to the 13q12 locus. CONCLUSIONS: These genome-wide LD screening data suggest that several AD-associated chromosomal loci exist, which may encompass novel susceptibility genes for late-onset AD. Therefore, extensive screening of the genes located in the vicinity of these LD regions is necessary to elucidate their role in AD.

Age of Onset↗

Transmission of Mycobacterium tuberculosis through casual contact with an infectious case.

BACKGROUND: An ongoing restriction fragment length polymorphism study of Mycobacterium tuberculosis isolates from tuberculosis cases showed an identical 12-band IS6110 pattern unique to 3 unrelated patients (Patients A-C) diagnosed as having tuberculosis within a 9-month period. METHODS: In an attempt to identify epidemiologic links between the 3 patients, we performed site visits to the retail business work site of patient A and conducted detailed interviews with all 3 patients and their contacts. RESULTS: Patient B had visited patient A's work site 3 times during patient A's infectious period, spending no more than 15 minutes each time. Patient C visited patient A's work site on 6 to 10 occasions during this period for no more than 45 minutes at any one time. There were no other epidemiologic links between these 3 cases other than the contact at the store. Contact investigation identified 4 tuberculin skin test conversions among 8 (50%) of patient A's coworkers, 6 positive tests among 15 household contacts (40%), and 8 positive tests among 16 identified customers who were casual contacts (50%). Patient B and patient C were most likely infected by patient A during one of their brief visits to patient A's work site. CONCLUSIONS: These data demonstrate that some tuberculosis is spread through casual contact not normally pursued in traditional contact investigations and that, in certain situations, M tuberculosis can be transmitted despite minimal duration of exposure. In addition, this outbreak emphasizes the importance of DNA fingerprinting data for identifying unusual transmission in unexpected settings.

Adult↗

Site-directed mutagenesis and X-ray crystallography of the PQQ-containing quinoprotein methanol dehydrogenase and its electron acceptor, cytochrome c(L).

Two proteins specifically involved in methanol oxidation in the methylotrophic bacterium Methylobacterium extorquens have been modified by site-directed mutagenesis. Mutation of the proposed active site base (Asp303) to glutamate in methanol dehydrogenase (MDH) gave an active enzyme (D303E-MDH) with a greatly reduced affinity for substrate and with a lower activation energy. Results of kinetic and deuterium isotope studies showed that the essential mechanism in the mutant protein was unchanged, and that the step requiring activation by ammonia remained rate limiting. No spectrally detectable intermediates could be observed during the reaction. The X-ray structure, determined to 3 A resolution, of D303E-MDH showed that the position and coordination geometry of the Ca2+ ion in the active site was altered; the larger Glu303 side chain was coordinated to the Ca2+ ion and also hydrogen bonded to the O5 atom of pyrroloquinoline quinone (PQQ). The properties and structure of the D303E-MDH are consistent with the previous proposal that the reaction in MDH is initiated by proton abstraction involving Asp303, and that the mechanism involves a direct hydride transfer reaction. Mutation of the two adjacent cysteine residues that make up the novel disulfide ring in the active site of MDH led to an inactive enzyme, confirming the essential role of this remarkable ring structure. Mutations of cytochrome c(L), which is the electron acceptor from MDH was used to identify Met109 as the sixth ligand to the heme.

Alcohol Oxidoreductases↗

Karyometry of secretory cell nuclei in high-grade PIN lesions.

BACKGROUND: The goal of this study was a karyometric characterization of secretory cell nuclei in high-grade prostatic intraepithelial neoplasia (PIN) lesions. Specifically, the hypothesis is tested that distinctly different subgroups of nuclei exist in these lesions. METHODS: High-resolution images of 1,713 nuclei from high-grade PIN lesions were recorded. Karyometric features were computed. Discriminant function scores against normal reference nuclei, and nuclear abnormality values were derived. Data sets were processed by a nonsupervised learning algorithm to establish the presence of subgroups of nuclei with statistically different nuclear chromatin distributions. RESULTS: Three sets of nuclei were formed, facing an intact basal cell layer, a near vanishing basal cell layer, and a gap in the basal cell layer. For each set, a nonsupervised learning algorithm formed three statistically different subgroups of approximately equal sizes. Each subgroup is found in every one of the three sampling locations. The total optical density distribution of nuclei in two subgroups suggests an aneuploid distribution, the third subgroup has a near diploid distribution. CONCLUSIONS: Secretory cell nuclei in high-grade PIN lesions are a heterogeneous population, forming statistically different subgroups. Studies aimed at characterizing the progression of such lesions should consider the inhomogeneous nature of these nuclei.

Algorithms↗

Degradation of albumin in meningococcal sepsis.

We postulate that the proteolytic degradation of albumin into fragments could link the rapidity of the shock, rash, and hypocalcaemia associated with meningococcal sepsis. We examined urine of children with meningococcal disease and urine from control children with no sepsis and found albumin fragments of about 45 kDa, 25 kDa, and less than 20 kDa only in the urine of children with meningococcal sepsis and associated purpura. Exogenous or endogenous proteases, or both, may be released in severe meningococcal sepsis and, in association with an inadequate antiprotease response, result in albumin degradation. This may be a contributory factor to the rapid shock, hypocalcaemia, and rash seen in meningococcal sepsis.

Albumins↗

Health-related quality of life and health care costs in severe, refractory irritable bowel syndrome.

BACKGROUND: The irritable bowel syndrome (IBS) may lead to considerable impairment of health-related quality of life and high health care costs. It is not clear whether these poor outcomes directly result from severe bowel symptoms or reflect a coexisting psychiatric disorder. OBJECTIVE: To determine whether bowel symptom severity and psychological symptoms directly influence health-related quality of life and health care costs. DESIGN: Cross-sectional survey. SETTING: Secondary and tertiary gastroenterology clinics. PATIENTS: 257 patients with severe IBS who did not respond to usual treatments and were recruited for a trial of psychological treatment. MEASUREMENTS: Predictors were abdominal pain, entries in a diary of 10 IBS symptoms, and measures of psychological symptoms. Outcomes were inability to work, health-related quality of life (measured by Medical Outcomes Survey 36-item short-form questionnaire [SF-36] physical component summary scores), and health care and productivity costs. Predictor and outcome measures were compared by using multiple regression and logistic regression analyses. RESULTS: Abdominal pain occurred on average 24 days per month and activities were restricted on 145 days of the previous 12 months. The mean (+/-SD) Hamilton depression score was 11.3 +/- 6.1. The SF-36 physical component summary score was low (37.7 +/- 10.6), and the patients had incurred high health care costs ($1743 +/- $2263) over the previous year. Global severity and somatization scores on the Symptom Checklist 90 Revised, abdominal pain, and Hamilton depression scores independently contributed to the physical component score of the SF-36 (adjusted R(2) = 35.2%), but only psychological scores were associated with disability due to ill health. These variables did not accurately predict health care or other costs (adjusted R(2) = 9.3%). History of sexual abuse was not an independent predictor of outcome. CONCLUSIONS: Both abdominal and psychological symptoms are independently associated with impaired health-related quality of life in patients with severe IBS. Optimal treatment is likely to require a holistic approach. Since health care and loss of productivity costs are not clearly associated with these symptoms, alleviation of them will not necessarily lead to reduced costs.

Abdominal Pain↗

Variation in cancer risks, by mutation position, in BRCA2 mutation carriers.

Cancer occurrence in 164 families with breast/ovarian cancer and germline BRCA2 mutations was studied to evaluate the evidence for genotype-phenotype correlations. Mutations in a central portion of the gene (the "ovarian cancer cluster region" [OCCR]) were associated with a significantly higher ratio of cases of ovarian:breast cancer in female carriers than were mutations 5' or 3' of this region (P<.0001), extending previous observations. The optimal definition of the OCCR, as judged on the basis of deviance statistics, was bounded by nucleotides 3059-4075 and 6503-6629. The relative and absolute risks of breast and ovarian cancer associated with OCCR and non-OCCR mutations were estimated by a conditional likelihood approach, conditioning on the set of mutations observed in the families. OCCR mutations were associated both with a highly significantly lower risk of breast cancer (relative risk [RR] 0.63; 95% confidence interval (95% CI) 0.46-0.84; P=.0012) and with a significantly higher risk of ovarian cancer (RR = 1.88; 95% CI = 1.08-3.33; P=.026). No other differences in breast or ovarian cancer risk, by mutation position, were apparent. There was some evidence for a lower risk of prostate cancer in carriers of an OCCR mutation (RR = 0.52; 95% CI = 0.24-1.00; P=.05), but there was no evidence of a difference in breast cancer risk in males. By age 80 years, the cumulative risk of breast cancer in male carriers of a BRCA2 mutation was estimated as 6.92% (95% CI = 1.20%-38.57%). Possible mechanisms for the variation in cancer risk are suggested by the coincidence of the OCCR with the RAD51-binding domain.

Adult↗

Golf course development in a major tourist destination: implications for planning and management.

The planning and design of golf course developments is influenced by many factors. This paper focuses on the environmental ramifications of insufficient or lack of compliance with standard environmental and economic planning practices. Specifically, it looks at a tourist destination location that was under the influence of extensive land development and investment speculation. The Gold Coast in Australia was the focal point for large overseas investment due to changes in government legislation regarding foreign investment. Due to the economic climate in the second half of the 1980s many golf course resort developments were built, approved, or planned. Many of these circumvented normal business and environment planning processes. The result has been a dangerous concentration of golf facilities in environmentally sensitive areas and an oversupply of golf facilities. Both of these matters are discussed in terms of the general planning process and the potential economic and environmental impacts to the Gold Coast and similar destinations in other parts of the world.

Commerce↗

Body mass index and future healthcare costs: a retrospective cohort study.

OBJECTIVE: To assess the relationship between body mass index (BMI) and future healthcare costs. RESEARCH METHODS AND PROCEDURES: We undertook a retrospective cohort study of the relationship between obesity and future healthcare costs at Kaiser Permanente Northwest Division, a large health maintenance organization in Portland, Oregon. Study subjects (n = 1286) consisted of persons who responded to a 1990 health survey that was mailed to a random sample of adult Kaiser Permanente Northwest Division members who were 35 to 64 years of age; had a BMI > or = 20 kg/m(2) (based on self-reported height and weight); did not smoke cigarettes; and did not have a history of coronary heart disease, stroke, human immunodeficiency virus, or cancer. Subjects were stratified according to their BMI in 1990 (20 to 24.9, 25 to 29.9, and > or = 30 kg/m(2); n = 545, 474, and 367, respectively). We then tallied their costs (in 1998 US dollars) for all inpatient care, outpatient services, and prescription drugs over a 9-year period (1990 through 1998). RESULTS: For persons with BMIs of 20 to 24.9 kg/m(2), mean (+/-SE) annual costs of prescription drugs, outpatient services, inpatient care, and all medical care averaged $261 (+/-18), $848 (+/-59), $532 (+/-85), and $1631 (+/-120), respectively, over the study period. Cost ratios (95% confidence intervals) for persons with BMIs of 25 to 29.9 kg/m(2) and > or = 30 kg/m(2), respectively, were 1.37 (1.12 to 1.66) and 2.05 (1.62 to 2.55) for prescription drugs, 0.96 (0.83 to 1.13) and 1.14 (0.97 to 1.37) for outpatient services, 1.20 (0.81 to 1.86) and 1.38 (0.91 to 2.14) for inpatient care, and 1.10 (0.91 to 1.35) and 1.36 (1.11 to 1.68) for all medical care. DISCUSSION: Future healthcare costs are higher for persons who are overweight, especially those with BMIs > or = 30 kg/m(2).

Adult↗

The human oesophageal squamous epithelium exhibits a novel type of heat shock protein response.

The human oesophageal epithelium is subject to damage from thermal stresses and low extracellular pH that can play a role in the cancer progression sequence, thus identifying a physiological model system that can be used to determine how stress responses control carcinogenesis. The classic heat shock protein HSP70 is not induced but rather is down-regulated after thermal injury to squamous epithelium ex vivo; this prompted a longer-term study to address the nature of the heat shock response in this cell type. An ex vivo epithelial culture system was subsequently used to identify three major proteins of 78, 70, and 58 kDa, whose steady-state levels are elevated after heat shock. Two of the three heat shock proteins were identified by mass spectrometric sequencing to be the calcium-calmodulin homologue transglutaminase-3 (78 kDa) and a recently cloned oesophageal-specific gene called C1orf10, which encodes a 53-kDa putative calcium binding protein we have named squamous epithelial heat shock protein 53 (SEP53). The 70-kDa heat shock protein (we have named SEP70) was not identifiable by mass spectrometry, but it was purified and studied immunochemically to demonstrate that it is distinct from HSP70 protein. Monoclonal antibodies to SEP70 protein were developed to indicate that: (a) SEP70 is induced by exposure of cultured cells to low pH or glucose starvation, under conditions where HSP70 protein was strikingly down-regulated; and (b) SEP70 protein exhibits variable expression in preneoplastic Barrett's epithelium under conditions where HSP70 protein is not expressed. These results indicate that human oesophageal squamous epithelium exhibits an atypical heat shock protein response, presumably due to the evolutionary adaptation of cells within this organ to survive in an unusual microenvironment exposed to chemical, thermal and acid reflux stresses.

Amino Acid Sequence↗

The medical-care cost burden of obesity.

Recent years have seen a dramatic rise in the prevalence of obesity in many countries, stimulating interest in the health and economic consequences of this phenomenon. In this article, we provide a systematic review of the literature on the medical-care cost burden of obesity. Relevant studies were identified using a computerized search of the medical literature for English-language articles published between 1990 and 2001. The 18 studies that met all criteria for inclusion in the review can be classified as modelling or database studies and further distinguished as cross-sectional or longitudinal in nature. The majority of studies that have been conducted are cross-sectional modelling studies, including 10 studies reporting the burden of obesity to national health systems. These suggest that obesity accounts for 5.5-7.0% of national health expenditures in the United States and 2.0-3.5% in other countries for which estimates have been reported. Other studies highlight the burden of obesity from other perspectives, including employers and health plans, as well as the impact of obesity on future disease risks and associated medical-care costs. Despite various methodological limitations, discussed herein, this body of research leads to the inescapable conclusion that obesity exacts an immense economic toll in various countries throughout the world.

Cost of Illness↗

Muscle soreness and damage parameters after prolonged intermittent shuttle-running following acute vitamin C supplementation.

Exercise-induced free-radical production may be partly responsible for muscle soreness and damage following demanding exercise. A number of studies have investigated the effect of antioxidant supplementation although there is a paucity of information regarding vitamin C. Therefore the aim of the present study was to investigate the effect of vitamin C supplementation on exercise-induced muscle soreness and damage. Nine habitually active males consumed a 1 g dose of vitamin C 2 h before exercise, and on another occasion consumed an identical placebo. The exercise comprised a 90 min intermittent shuttle-running test, which was designed to simulate the multiple-sprint sports. Vitamin C supplementation increased plasma concentrations of vitamin C before exercise, and plasma concentrations continued to increase during the shuttle-run to reach a peak of approximately 200 micromol x l(-1) immediately after exercise. However, muscle soreness, and markers of both muscle damage (creatine kinase and aspartate aminotransferase) and lipid peroxidation (malondialdehyde) were elevated to an equal extent after exercise in placebo and supplemented trials. Therefore acute supplementation with vitamin C had no beneficial effects although it is possible that such short-term vitamin C supplementation was ineffective because it occurred at an inappropriate time.

Administration, Oral↗

Item-cued directed forgetting of related words and pictures in children and adults: selective rehearsal versus cognitive inhibition.

The main purpose of this study was to compare the relative importance of selective rehearsal and cognitive inhibition in accounting for developmental changes in the directed-forgetting paradigm developed by R. A. Bjork (1972). In two experiments, children in Grades 2 and 5 and college students were asked to remember some words or pictures and to forget others when items were categorically related. Their memory for both items and the associated remember or forget cues was then tested with recall and recognition. Fifth graders recognized more of the forget-cued words than college students did. The pattern of results suggested that age differences in rehearsal and source monitoring (i.e., remembering whether a word had been cued remember or forget) were better explanatory mechanisms for children's forgetting inefficiencies than retrieval inhibition was. The results are discussed in terms of a multiple process view of inhibition.

Adolescent↗

Test anxiety, coping strategies, and perceived health in a group of high school students: a Turkish sample.

A group of high school juniors and a group of high school seniors in Izmir, Turkey completed measures of test anxiety, coping skills, and perceived health status both before and after a major exam period. Students with high test anxiety used less effective coping mechanisms and tended to have poorer perceptions of their health. Prior to the exams, juniors displayed higher test anxiety and used less effective coping mechanisms than seniors. After the exam periods, improvements were seen for both age groups on perceived health, but scores of younger students remained significantly higher than scores of seniors on one of the key measures of test anxiety. Results of the study lend support to those of previous studies done in other cultural contexts, and findings have implications for the development of interventions designed to help students cope with stress.

Adaptation, Psychological↗

A comparison of smoking behaviours between patients treated with clozapine and depot neuroleptics.

The high prevalence of smoking among individuals diagnosed with schizophrenia is well recognized and documented. Many explanations have been put forth to explain this phenomenon including the effects of antipsychotic medication. We sought to determine if there is a difference in smoking behaviour between patients treated with clozapine and depot neuroleptics. This cross-sectional study recruited patients with schizophrenia from the Forensic Psychiatric Institute of British Columbia. Eligibility for the study required that patients be on either clozapine or depot neuroleptic for at least 2 months. The patient's smoking behaviour was evaluated using expired carbon monoxide (CO) measurements, the Fagerstrom Test for Nicotine Dependence (FTND), and a semi-structured interview. Our results showed that patients treated with clozapine had significantly lower expired CO values than patients treated with depot neuroleptics (11.8 +/- 9.2 versus 21.2 +/- 7.1 p.p.m., respectively, P < 0.01). This finding was further supported by the noted trend in which patients receiving clozapine self-reported smoking less than patients treated with depot neuroleptics (13.7 +/- 11.3 versus 26.8 +/- 18.3 cigarettes per day, respectively, P = 0.08). Thus, according to measurements of expired CO levels, patients treated with clozapine smoke less than patients treated with depot neuroleptics.

Adult↗

Peak power output, the lactate threshold, and time trial performance in cyclists.

PURPOSE: To determine the relationship between maximum workload (W(peak)), the workload at the onset of blood lactate accumulation (W(OBLA)), the lactate threshold (W(LTlog)) and the D(max) lactate threshold, and the average power output obtained during a 90-min (W(90-min)) and a 20-min (W(20-min)) time trial (TT) in a group of well-trained cyclists. METHODS: Nine male cyclists (.VO(2max) 62.7 +/- 0.8 mL.kg(-1).min(-1)) who were competing regularly in triathlon or cycle TT were recruited for the study. Each cyclist performed four tests on an SRM isokinetic cycle ergometer over a 2-wk period. The tests comprised 1) a continuous incremental ramp test for determination of maximal oxygen uptake (.VO(2max) (L.min(-1) and mL.kg(-1).min(-1)); 2) a continuous incremental lactate test to measure W(peak), W(OBLA), W(LTlog), and the D(max) lactate threshold; and 3) a 20-min TT and 4) a 90-min TT, both to determine the average power output (in watts). RESULTS: The average power output during the 90-min TT (W(90-min)) was significantly (P < 0.01) correlated with W(peak) (r = 0.91), W(LTlog) (r = 0.91), and the D(max) lactate threshold (r = 0.77, P < 0.05). In contrast, W(20-min) was significantly (P < 0.05) related to .VO(2max) (L.min(-1)) (r = 0.69) and W(LTlog) (r = 0.67). The D(max) lactate threshold was not significantly correlated to W(20-min) (r = 0.45). Furthermore, W(OBLA) was not correlated to W(90-min) (r = 0.54) or W(20-min) (r = 0.23). In addition, .VO(2max) (mL.kg(-1).min(-1)) was not significantly related to W(90-min) (r = 0.11) or W(20-min) (r = 0.47). CONCLUSION: The results of this study demonstrate that in subelite cyclists the relationship between maximum power output and the power output at the lactate threshold, obtained during an incremental exercise test, may change depending on the length of the TT that is completed.

Adult↗