Search PubMed⌕ Search

Biomedical subjects

D Thompson

Publications and source records attributed to D Thompson.

At least 163 records · Page 9Linked to original sources

Computer-assisted discrimination of glioblastomas.

OBJECTIVE: To measure a number of nuclear features in a series of glioblastomas and compare the data with those from a set of anaplastic and low grade astrocytomas. STUDY DESIGN: The material consisted of toluidine blue-stained smears from 13 consecutive cases of glioblastoma. Smears from 12 high grade astrocytomas and 13 low grade fibrillary astrocytomas were used for comparison. Fifty nuclei were measured in each case. Cell images were segmented by an interactive procedure. A set of features representing both morphometric and nuclear texture characteristics was computed. RESULTS: The use of a discriminant function based on two features related to the gray value distribution resulted in the separation of all low grade astrocytomas from glioblastomas. When the corresponding discriminant function was computed for high grade astrocytomas and the values were plotted against optical density, the glioblastomas formed a group at a greater distance from the low grade astrocytomas than from the high grade astrocytomas. A second discriminant function based on two features allowed complete separation of the glioblastoma cases from the high grade astrocytomas. CONCLUSION: In our material, chromatin texture analysis allowed effective separation of astrocytic tumors with different histologic grades of malignancy.

Astrocytoma↗

Computer-assisted analysis of medulloblastoma. A cytologic study.

OBJECTIVE: To explore data from a set of cases of medulloblastoma to see whether quantitative image analysis might suggest evidence for the existence of lower and higher grade lesions. STUDY DESIGN: Fourteen consecutive cases of medulloblastoma were obtained. Smears were stained with toluidine blue. For each case, 50 nuclei were measured and a number of densitometric features extracted. RESULTS: The existence of two subgroups of cases, identified as lower and higher grade groups, was suggested by a plot of the total optical density versus nuclear area. Two nuclear texture features--the number of pixels with the same optical density value occurring consecutively in the nucleus and the proportion of pixels in the high optical density range--divided the cases into the same subgroups. The use of a clustering algorithm established two clusters that corresponded to that subgrouping except for one case. Discriminant analysis gave an identical classification, with the misplaced case having a borderline discriminant function score. An unsupervised learning algorithm based on an adaptive distance metric formed two clusters and assigned the borderline case to the low grade subgroup. The grouping obtained by quantitative analysis was only partly related to the grade of nuclear atypia subjectively evaluated. CONCLUSION: In our series of medulloblastomas, quantitative analysis provided a means of detecting differences in the nuclear size and texture that allowed the classification of cases into two subgroups.

Adult↗

The regulatory role for magnesium in glycolytic flux of the human erythrocyte.

31P NMR was used to measure the intracellular free magnesium concentration ([Mg2+]i) in human erythrocytes while [Mg2+]i was changed between 0.01 and 1.2 mM using the divalent cationophore A23187. 13C NMR and [2-13C]glucose were used to determine the kinetic effects of [Mg2+]i by measuring the flux through several parts of the glucose pathway. Glucose utilization was strongly dependent on [Mg2+]i, with half-maximal flux occurring at 0.03 mM. The rate-limiting step was most likely at phosphofructokinase, which has a Km(Mg2+) of 0.025 mM in the purified enzyme. Phosphorylated glycolytic intermediate concentration was also strongly dependent on [Mg2+]i and [MgATP], and glucose transport plus hexokinase may have been partially rate-determining at [Mg2+]i below approximately 0.1 mM. The pentose phosphate shunt activity was too low to determine the dependence on [Mg2+]i. Phosphoglycerate kinase and 2, 3-diphosphoglycerate mutase fluxes were also measured, but were not rate-limiting for glycolysis and showed no Mg2+ dependence. Human erythrocyte [Mg2+]i varies between 0.2 mM (oxygenated) and 0.6 mM (deoxygenated), well above the measured [Mg2+]i(1/2). It is unlikely, then, that [Mg2+]i plays a regulatory role in normal erythrocyte glycolysis.

Bisphosphoglycerate Mutase↗

Collaborating on the integration of cancer nursing services.

This article outlines the proposals contained in the Calman-Hine report (DoH 1995), and then presents the work of a nursing task group set up in response to its recommendations. The authors describe how different agencies collaborated in a network approach to improving the provision of cancer services.

Breast Neoplasms↗

Use of terfenadine and contraindicated drugs.

OBJECTIVE: To assess changes in concurrent use of products containing terfenadine and contraindicated macrolide antibiotics (erythromycin, clarithromycin, troleandomycin) and imidazole antifungals (ketoconazole, itraconazole) following reports of serious drug-drug interactions and changes in product labeling. DESIGN: Retrospective review of computerized pharmacy claims. SETTING: A large health insurer in New England. PATIENTS: Health plan members with 1 or more paid pharmacy claims for products containing terfenadine between January 1990 and June 1994. MAIN OUTCOME MEASURES: Among persons with paid claims for terfenadine in any given month, percentage with a prescription for any contraindicated drug that alternatively was dispensed on the same day as ("same-day dispensing") or had therapy days that overlapped those of ("overlapping use") a prescription for terfenadine. RESULTS: Concurrent use of terfenadine and contraindicated drugs declined over the study period. The rate of same-day dispensing declined by 84% from an average of 2.5 per 100 persons receiving terfenadine in 1990 to 0.4 per 100 persons during the first 6 months of 1994, while the rate of overlapping use declined by 57% (from 5.4 to 2.3 per 100 persons). Most cases involved erythromycin. CONCLUSIONS: Despite substantial declines following reports of serious drug-drug interactions and changes in product labeling, concurrent use of terfenadine and contraindicated macrolide antibiotics and imidazole antifungals continues to occur.

Anti-Bacterial Agents↗

Illegal poisoning.

Explore the source record for details and available documents.

Animal Welfare↗

Purine deoxynucleoside metabolism in human melanoma cells with a high spontaneous mutation rate.

A human melanoma cell line (MM96L) had a spontaneous mutation rate at the HGPRT locus of approx. 7 times normal. The cells had elevated dATP and dGTP pools, lacked purine nucleoside phosphorylase (PNP) and were sensitive to killing by deoxyadenosine, deoxyinosine and related purines but not to inosine or hypoxanthine. Four other melanoma cell lines exhibited a range of nucleoside sensitivities and dNTP pool sizes. Failure of intact MM96L cells to degrade exogenous deoxyadenosine and deoxyinosine to hypoxanthine was confirmed by NMR of culture medium. Normal melanocytes were PNP+ and were insensitive to deoxyinosine. Comparison of the metabolites of [14C]deoxyinosine from MM96L and a PNP+ cell line of similar doubling time (HeLa) showed that both cell types produced 14C-labelled guanine and adenine nucleotides, with [14C]dATP and [14C]dADP being found in MM96L. This indicates that human sAMP synthetase or a similar enzyme catalyses the conversion of dIMP to dAMP, the resultant elevation of dATP causing base misincorporation and a mutator phenotype.

Alanine↗

The use of mechanistically defined chemical mixtures (MDCM) to assess mixture component effects on the percutaneous absorption and cutaneous disposition of topically exposed chemicals. II. Development of a general dermatopharmacokinetic model for use in risk assessment.

We present a conceptual approach to a general comprehensive mathematical model to quantify percutaneous absorption of topically applied chemicals in complex mixtures on the basis of biophysical parameters estimated or measured using in vitro and ex vivo perfused skin preparations. This model addresses mechanistically defined chemical mixtures (MDCM) which consist of components selected because of their potential to modulate by various mechanisms the absorption of a marker toxic penetrant. This model accounts for observed toxicodynamic general and specific effects of chemicals, acting single or in concert, on the absorption of any or all components in a defined mixture. We have also included experimental data from an isolated perfused porcine skin flap study with topically applied parathion as the marker penetrant and acetone or DMSO as solvent, with methyl nicotinate as a potential rubefacient, sodium laurel sulfate as a surfactant, and stannous chloride as a reducing agent in order to provide an illustration of the application and performance of the model. This model supports the MDCM concept that defining and then simulating those components of a complex mixture that could have a significant impact on the absorption of a marker toxic compound would be a useful screening approach in the risk assessment of topical chemical mixtures. It may also be used to identify critical pathways where chemical mixture component interactions significantly modify the absorption of the penetrant of interest.

Animals↗

Treatment of obstructive sleep apnoea using nasal CPAP in children with craniofacial dysostoses.

We studied a group of children (aged 2.2-15 years) with craniofacial dysostosis and obstructive sleep apnoea to assess the use of nasal continuous positive airway pressure (n-CPAP) as a palliative form of treatment. A variable period of time was allowed for acclimatisation to n-CPAP (1 day to 2 months), depending on the patient. Patients were then admitted for their first CPAP trial. Baseline breathing difficulty and the effectiveness of n-CPAP were assessed by respiratory sleep studies. Successful results were obtained with n-CPAP in five of the eight patients, with marked clinical and polygraphic improvements of the respiratory pattern immediately after n-CPAP was established. Of the remaining three cases, one child needed a prolonged period of acclimatisation to the n-CPAP system, one was withdrawn from the study, and one failed to respond to n-CPAP and was found to have complete blockage of the upper airways as a result of enlarged adenoids. Our results confirm that n-CPAP can be tolerated even by young patients and can be effective, and that it may be a useful alternative palliative treatment for obstructive sleep apnoea in children with craniofacial syndromes.

Adolescent↗

Body size accounts for most differences in bone density between Asian and Caucasian women. The EPIC (Early Postmenopausal Interventional Cohort) Study Group.

We compared bone mineral density (BMD) of the whole body (and subregions: arm, leg, and pelvis), hip, spine, lateral spine, wrist, and forearm among Caucasian and Asian women at four geographic centers (Honolulu, HI; Nottingham, UK; Portland, OR; Copenhagen, Denmark). Data were derived from the baseline examination of 1367 Caucasian and 162 Asian women enrolled in the 1609-subject Early Postmenopausal Interventional Cohort (EPIC) study. After adjusting for age, study site, years postmenopause, and years of estrogen use, BMD was approximately 4-6% lower (P < 0.05) among Asian women at most skeletal sites, but there was no significant difference for wrist or forearm BMD. Adding height, lean body mass, fat mass, and/or quadriceps muscle strength to the regression models reduced the racial differences at most skeletal sites; after these additional adjustments, Asian women had significantly lower BMD only for the lateral spine (-4.4%; P < 0.005), arm (-2.20%; P < 0.05) and leg (-1.65%; P < 0.05), whereas the wrist was significantly greater (4.64%; P < 0.005) for Asian women. Further research is needed to determine why racial differences in BMD persist at certain skeletal sites, but not others, after adjusting for body size.

Anthropometry↗

Estimated effects of reducing dietary saturated fat intake on the incidence and costs of coronary heart disease in the United States.

OBJECTIVES: To estimate the effects of reducing dietary saturated fat intake on the incidence and economic costs of coronary heart disease (CHD) in the United States. DESIGN: Modeling techniques and data from secondary sources, including the Framingham Heart Study and the second and third National Health and Nutrition Examination Surveys, were used to estimate the effects on CHD incidence and associated costs of reducing dietary saturated fat intake as a percent of total energy by one to three percentage points. SUBJECTS: Persons aged 35 to 69 years who have total cholesterol levels of 5.17 mmol/L or higher and are currently free of CHD. RESULTS: Approximately 3 million first-time coronary events are estimated to occur over a 10-year period among persons with total cholesterol levels exceeding 5.17 mmol/L. Reducing saturated fat intake by one to three percentage points would reduce CHD incidence by 32,000 to 99,700 events and yield combined savings in medical expenditures and lost earnings ranging from $4.1 to $12.7 billion over 10 years (estimates in 1993 US dollars). CONCLUSION: Population-based interventions to encourage Americans to reduce dietary intake of saturated fat may prevent tens of thousands of cases of CHD and save billions of dollars in related costs.

Adult↗

Atypical adenomatous hyperplasia (adenosis) of the prostate: development of a Bayesian belief network for its distinction from well-differentiated adenocarcinoma.

The diagnosis of atypical adenomatous hyperplasia (AAH) of the prostate and its distinction from well-differentiated prostatic adenocarcinoma with small acinar pattern (PACsmac; Gleason primary grades 1 or 2) are affected by uncertainties that arise from the fact that the knowledge of AAH histopathology is expressed in descriptive linguistic terms, words, and concepts. A Bayesian belief network (BBN) was used to reduce the problem of uncertainty in diagnostic clue assessment, while still considering the dependencies between elements in the reasoning sequence. A shallow network was designed and developed with an open-tree topology, consisting of a root node containing two diagnostic alternatives (eg, AAH v PACsmac) and 12 first-level descendant nodes for the diagnostic features. Eight of these nodes were based on cell features, three on the type of gland lumen contents and one on the gland shape. The results obtained with prototypes of relative likelihood ratios showed that belief for the diagnostic alternatives is high and that the network can differentiate AAH from PACsmac with certainty. The features that best contributed to the highest belief were those concerning the nucleolar size, frequency, and location. In particular, after the analysis of five nucleolar features (prominent nucleoli, inconspicuous nucleoli, nucleoli with diameter greater than 2.5 micron, nucleolar margination, and nuclei with multiple nucleoli), the belief for AAH was 1.0, being already close to 1.0 when three were evaluated (the value range is 0.0 to 1.0; the closer to 1.0, the greater the belief). The contribution of the three features concerning the gland lumen contents (mucinous material, corpora amylacea, and crystalloids) was such that the final belief did not exceed 0.8. Results with the group of remaining features (eg, basal cell recognition, gland shape variation, cytoplasm appearance, and nuclear size variation) were slightly better. These features allowed a substantial accumulation of belief that was already greater than 0.9 when three were polled. However, the maximum belief value was never obtained. In conclusion, a BBN for AAH diagnosis offers a descriptive classifier that is readily implemented, and allows the use of linguistic, fuzzy variables, and the accumulation of evidence presented by diagnostic clues.

Adenocarcinoma↗

Quantitative study of ductal breast cancer progression. A progression index (P.I.) for premalignant lesions and in situ carcinoma.

The diagnostic subjective assessment of ductal premalignant proliferative lesions and in situ carcinoma of the breast produces unsatisfactory results. Since the phenotypical cell changes in tumour progression toward infiltrating cancer constitute a continuum, a grading on a continuous scale of values produces a more reliable and reproducible characterization. The diagnostic assessment for any individual patient may be expressed by a progression index (P.I.): its numerical values are based on the cellular changes measured in the individual cases. In this study, the progression index is based on two morphometric features, nuclear size and nucleolar area. In addition, the method presented may produce a ratio, stating the relative likelihood that each case represents one of the conventional diagnostic categories. Such a likelihood ratio may be obtained from the bivariate distribution of nuclear size and nucleolar area for the conventional diagnostic categories.

Breast Neoplasms↗