Biomedical subjects

D Coleman

Publications and source records attributed to D Coleman.

At least 37 records · Page 2Linked to original sources

PubMed2000

Relationship between ultrasound texture classification images and histology of atherosclerotic plaque.

Structure and content of atherosclerotic plaque varies between patients and may be indicative of their risk for embolisation. This study aimed to construct parametric images of B-scan texture and assess their potential for predicting plaque morphology. Sequential transverse in vitro scans of 10 carotid plaques, excised during endarterectomy, were compared with macrohistology maps of plaque content. Multidiscriminant analysis combined the output of 157 statistical and textural algorithms into five separate texture classes, displayed as ultrasound (US) texture classification images (UTCI). Visual comparison between corresponding UTCI and histology maps found the five texture classes matched with the location of fibrin, elastin, calcium, haemorrhage or lipid. However, histology preparation removes calcium and lipid and, so, can affect the structural integrity of atherosclerotic plaques. Soft tissue regions smaller than the UTCI kernel, (0.87 mm x 0.85 mm x 3.9 mm), such as blood clots, are also difficult to detect by UTCI. These factors demonstrate limitations in the use of histology as a "gold standard" for US tissue characterisation.

Arteriosclerosis↗

PubMed2000

Causes of inconsistency in diagnosing and classifying intraductal proliferations of the breast. European Commission Working Group on Breast Screening Pathology.

It is now widely recognised that classifying ductal carcinoma in situ (DCIS) of the breast and diagnosing atypical ductal hyperplasia are associated with significant interobserver variation. Two possible reasons for this inconsistency are differences in the interpretation of specified histological features and field selection where morphology is heterogeneous. In order to investigate the relative contribution of these two factors to inconsistent interpretation of intraductal proliferations, histological sections of 32 lesions were sent to 23 European pathologists followed 3 years later by images of small parts of these sections. Kappa statistics for diagnosing hyperplasia of usual type, atypical ductal hyperplasia and ductal carcinoma in situ were 0.54, 0.35 and 0.78 for sections and 0.47, 0.29 and 0.78 for images, respectively, showing that most of the inconsistency is due to differences in morphological interpretation. Improvements can thus be expected only if diagnostic criteria or methodology are changed. In contrast, kappa for classifying DCIS by growth pattern was very low at 0.23 for sections and better at 0.47 for images, reflecting the widely recognised variation in the growth pattern of DCIS. Higher kappa statistics were obtained when any mention of an individual growth pattern was included in that category, thus allowing multiple categories per case; but kappa was still higher for images than sections. Classifying DCIS by nuclear grade gave kappa values of 0.36 for sections and 0.49 for images, indicating that intralesional heterogeneity has hitherto been underestimated as a cause of inconsistency in classifying DCIS by this method. More rigorous assessment of the proportions of the different nuclear grades present could lead to an improvement in consistency.

Breast↗

PubMed2000

The biogeochemical controls of N2O production and emission in landfill cover soils: the role of methanotrophs in the nitrogen cycle.

Emissions of N2O from cover soils of both abandoned (> 30 years) and active landfills greatly exceed the maximum fluxes previously reported for tropical soils, suggesting high microbial activities for N2O production. Low soil matrix potentials (<-0.7 MPa) indicate that nitrification was the most likely mechanism of N2O formation during most of the time of sampling. Soil moisture had a strong influence on N2O emissions. The production of N2O was stimulated by as much as 20 times during laboratory incubations, when moisture was increased from -2.0 MPa to -0.6 MPa. Additional evidence from incubation experiments and delta13C analyses of fatty acids (18:1) diagnostic of methanotrophs suggests that N2O is formed in these soils by nitrification via methanotrophic bacteria. In a NH3(g)-amended landfill soil, the rate of N2O production was significantly increased when incubated with 100 ppmv methane compared with 1.8 ppmv (atmospheric) methane. Preincubation of a landfill soil with 1% CH4 for 2 weeks resulted in higher rates of N2O production when subsequently amended with NH3(g) relative to a control soil preincubated without CH4. At one location, at the soil depth (9-16 cm) of maximum methane consumption and N2O production, we observe elevated concentrations of organic carbon and nitrogen and distinct minima in delta15N (+1.0%) and delta13C (-33.8%) values for organic nitrogen and organic carbon respectively. A delta13C value of -39.3% was measured for 18:1 carbon fatty acids in this soil, diagnostic of type II methanotrophs. The low delta15N value for organic nitrogen is consistent with N2 fixation by type II methanotrophs. These observations all point to a methanotrophic origin for the organic matter at this depth. The results of this study corroborate previous reports of methanotrophic nitrification and N2O formation in aqueous and soil environments and suggest a predominance of type II rather than type I or type X methanotrophs in this landfill soil.

Euryarchaeota↗

PubMed2000

Correlates of simulated hill climb cycling performance.

The aim of this study was to assess the relationship between several commonly used aerobic and anaerobic cycle ergometer tests and performance during a treadmill cycling hill climb. Eight competitive cyclists (age 27+/-7 years; body mass 73.2+/-5.2 kg; height 177+/-6 cm; mean +/- s) completed six tests in random order: a lactate minimum test; a Wingate anaerobic power test; and two 6-km climbs at 6% and two 1-km climbs at 12% gradient performed on a motorized treadmill. The mean times and power outputs for the 6-km and 1-km climbs were 16:30+/-1:08 min: s and 330+/-17.8 W, and 4:19+/-0:27 min: s and 411+/-24.4 W, respectively. The best individual predictor of 6-km and 1-km performance times was the time for the corresponding climb at the other distance (r = 0.97). The next strongest predictor of both hill climb performances was the average power produced during the Wingate test divided by body mass. Stepwise regression analysis showed that the two variables contributing most to the prediction equation for both climbs were the Wingate average power per unit of body mass and maximal aerobic power divided by total mass (rider + bike), which together accounted for 92 and 96% of the variability in the 6-km and 1-km climbs. In conclusion, among competitive cyclists, the Wingate average power per unit of body mass was the best single predictor of simulated cycling hill climb performance at the distance and gradient used.

Adaptation, Physiological↗

PubMed2000

Assessment of blood lactate: practical evaluation of the Biosen 5030 lactate analyzer.

PURPOSE: The aim of this study was to assess the validity and reliability of the Biosen 5030 lactate analyzer compared with a YSI 2300 lactate analyzer and a Kodak Ektachem DTII in a practical laboratory study context. METHODS: To assess validity, 144 triplicate capillarized blood samples, across a range of values, were analyzed using the three analyzers. To assess reliability a further 665 samples were repeat analyzed. Temporal stability was determined by the reanalysis of resting and maximal exercise blood samples, after a period of storage ranging from 7 to 20 h, at room temperature. To measure inter- and intra-investigator reliability, 20 resting samples were taken from three different subjects by different investigators and a coefficient of variation was determined. RESULTS: There were strong relationships between the Biosen, the YSI (r2 = 0.97), and the Kodak Ektachem (r2 = 0.91). An analysis of Biosen compared with YSI revealed a positive bias of 0.37 mmol x L(-1) (95% limits of agreement, -0.85 to 1.59 mmol x L(-1)). The test-retest reliability correlation was significant (r2 = 0.99, P < 0.05), but a paired t-test revealed a small (0.03 mmol x L(-1), P < 0.05) significant difference. The coefficient of variation from the three investigators across the 20 samples ranged from 1.3 to 3%. Blood lactate concentration in resting blood samples did significantly increase in value (0.2 mmol x L(-1), P < 0.05) after 7-h exposure to the air, whereas there was no change in maximal exercise blood lactate values after 20-h exposure to the air. CONCLUSIONS: In a practical context, the Biosen 5030 lactate analyzer was comparable to the other analyzers giving fast reliable measures of blood lactate concentrations over the full range of values, which remained stable over extended periods at room temperature.

Bias↗

PubMed2000

Ten-year review of a prospective randomized controlled trial of textured versus smooth subglandular silicone gel breast implants.

Although textured silicone breast implants have been shown to reduce the incidence of capsular contracture, there is little evidence if this effect is maintained in the long term. It has been 10 years since the double-blind randomized trial in which 53 patients received either Mentor smooth (26) or textured silicone gel implants (27). Of the 14 patients who were not known to have developed a contracture in the smooth group, 11 were reviewed. Three had bilateral contractures. In the textured group, 18 of the 24 patients not known to have contractures were reviewed. None had developed contractures. At 10 years, the incidence of capsular contracture was 65 percent of patients with smooth implants (an increase of 6 percent on the 3-year results) and 11 percent for the textured implant patients (no change on the 3-year results). A database containing the details of 1100 patients reinforces these results by examining the differences in contracture rates of textured, smooth, and polyurethane-coated implants. The effect of submuscular placement on reducing contracture rates regardless of texturing is discussed, as is the apparent increase in capsular contracture in patients who smoke.

Adult↗

PubMed2000

GO GIRLS!: results from a nutrition and physical activity program for low-income, overweight African American adolescent females.

This article describes the development, implementation, and results of an intervention designed for inner-city, overweight African American adolescent women. Fifty-seven participants were recruited from four public housing developments. Participants were administered physiologic, dietary, and cognitive assessments at baseline and immediately postintervention. Each session comprised three elements: (1) an educational/behavioral activity, (2) 30 to 60 minutes of physical activity, and (3) preparation and tasting of low-fat meals. In the absence of a control group, results were compared for high and low attenders, the former defined as attending at least 50% of the sessions. High attenders (n = 26) showed more favorable 6-month posttest values for most outcomes compared with low attenders (n = 31). These effects achieved statistical significance for nutrition knowledge, low-fat practices, perceived changes in low-fat practices, and social support.

Adolescent↗

PubMed2000

Involving families in an urban HIV preventive intervention: how community collaboration addresses barriers to participation.

This article addresses the increasing need within urban communities for effective, culturally relevant HIV prevention programs. The recruitment efforts of a family-based prevention program aimed at promoting health and preventing HIV risk exposure in urban, African American fourth and fifth grade children living in a community with high rates of HIV infection is detailed. The program, referred to as the CHAMP (Chicago HIV Prevention and Adolescent Mental Health Project) Family Program, is overseen by a collaborative partnership of community parents, school staff, and university-based researchers (Paikoff & McKay, 1995). The recruitment strategies developed as a result of this community-research collaboration are described. Preliminary results of the project's efforts to reach out to families within the targeted, inner-city community are presented.

Black or African American↗

PubMed1999

Induction of carcinoembryonic antigen (CEA)-specific cytotoxic T-lymphocyte responses in vitro using autologous dendritic cells loaded with CEA peptide or CEA RNA in patients with metastatic malignancies expressing CEA.

The application of dendritic cells (DC) to the active immunotherapy of cancer currently relies on the generation of potent DC capable of presenting tumor antigens such as carcinoembryonic antigen (CEA). It is unknown whether the T cells of patients with advanced malignancies can be reliably stimulated against tumor antigens by their autologous DC. In this study, starting with the peripheral blood mononuclear cells (PBMC) of patients with metastatic malignancies expressing CEA, autologous DCs were generated in vitro in serum-free media supplemented with GM-CSF and IL-4. The DCs from HLA A2 positive patients were loaded with the CEA peptide CAP-1 and the DCs from HLA A2 negative patients were depleted of bystander lymphocytes and loaded with mRNA encoding CEA. The DC preparations were tested to determine their phenotype and were used to stimulate autologous PBMC twice, separated by 10-14 days. The stimulated cells were then tested for their ability to lyse CEA-expressing target cells. We successfully generated an adequate number of DC for a clinical trial from all patients. The harvested DC preparations contained 49% DC and 87% DC if depleted of bystander lymphocytes. Phenotypic analysis showed the typical pattern of CD11c+ CD40+ CD86+ HLA-DR+ CD80(low) CD83(low) CD14(low). All preparations but one were able to stimulate CEA-specific cytotoxic T-lymphocyte (CTL) activity, suggesting that the majority of patients are not anergic to CEA and possess functional DC. The CTL activity was similar for the CEA peptide and CEA RNA-loaded DC.

Carcinoembryonic Antigen↗

PubMed1999

Constitutive calcium-independent release of Toxoplasma gondii dense granules occurs through the NSF/SNAP/SNARE/Rab machinery.

The signals and the molecular machinery mediating release of dense matrix granules from pathogenic protozoan parasites are unknown. We compared the secretion of the endogenous dense granule marker GRA3 in Toxoplasma gondii with the release of a stably transfected foreign reporter, beta-lactamase, that localizes to parasite dense granules. Both proteins were released constitutively in a calcium-independent fashion, as shown using both intact and streptolysin O-permeabilized parasites. N-Ethylmaleimide and recombinant bovine Rab-guanine dissociation inhibitor inhibited beta-lactamase secretion in permeabilized parasites, whereas recombinant hamster N-ethylmaleimide-sensitive fusion protein and bovine alpha-SNAP augmented release. Guanosine 5'-3-O-(thio)triphosphate, but not cAMP, augmented secretion in the presence but not in the absence of ATP. The T. gondii NSF/SNAP/SNARE/Rab machinery participates in dense granule release using parasite protein components that can interact functionally with their mammalian homologues.

Animals↗

PubMed1999

Migration of human dendritic cells after injection in patients with metastatic malignancies.

Present clinical studies of active immunotherapy for malignancies using dendritic cells (DCs) require elucidation of the sites where DCs localize after injection. We evaluated the pattern of distribution of in vitro-generated, antigen-loaded, human DCs labeled with indium-111 oxyquinoline after i.v., s.c., and intradermal injection. Whereas the DCs injected i.v. localized in the lungs and then redistributed to the liver, spleen, and bone marrow, they were not detected in lymph nodes or tumors. A small percentage of DCs injected intradermally migrated rapidly to the regional lymphatics in some individuals. No lymph node activity was detected after s.c. injection. Our results demonstrate that DC distribution to sites of lymphoid tissue is dramatically affected by the mode of administration.

Cell Movement↗

PubMed1999

Consistency achieved by 23 European pathologists from 12 countries in diagnosing breast disease and reporting prognostic features of carcinomas. European Commission Working Group on Breast Screening Pathology.

A detailed analysis of the consistency with which pathologists from 12 different European countries diagnose and classify breast disease was undertaken as part of the quality assurance programme of the European Breast Screening Pilot Network funded by the Europe against Cancer Programme. Altogether 107 cases were examined by 23 pathologists in 4 rounds. Kappa statistics for major diagnostic categories were: benign (not otherwise specified) 0.74, atypical ductal hyperplasia (ADH) 0.27, ductal carcinoma in situ (DCIS) 0.87 and invasive carcinoma 0.94. ADH was the majority diagnosis in only 2 cases but was diagnosed by at least 2 participants in another 14, in 9 of which the majority diagnosis was benign (explaining the relatively low kappa for this category). DCIS in 4 (all low nuclear grade) and invasive carcinoma (a solitary 1-mm focus) in 1. The histological features of these cases were extremely variable; although one feature that nearly all shared was the presence of cells with small, uniform, hyperchromatic nuclei and a high nucleo-cytoplasmic ratio. The majority diagnosis was DCIS in 33 cases; kappa for classifying by nuclear grade was 0.38 using three categories and 0.46 when only two (high and other) were used. When ADH was included with low nuclear grade DCIS there was only a slight improvement in kappa. Size measurement of DCIS was less consistent than that of invasive carcinoma. The majority diagnosis was invasive carcinoma in 57 cases, the size of the majority being 100% in 49. The remainder were either special subtypes (adenoid cystic, tubular, colloid, secretory, ductal/medullary) or possible microinvasive carcinomas. Subtyping was most consistent for mucinous (kappa, 0.92) and least consistent for medullary carcinomas (kappa, 0.56). Consistency of grading using the Nottingham method was moderate (kappa=0.53) and consistency of diagnosing vascular invasion, fair (kappa=0.38). There was no tendency for consistency to improve from one round to the next, suggesting that further improvements are unlikely without changes in guidelines or methodology.

Breast Diseases↗

PubMed1999

A Phase I study of active immunotherapy with carcinoembryonic antigen peptide (CAP-1)-pulsed, autologous human cultured dendritic cells in patients with metastatic malignancies expressing carcinoembryonic antigen.

Dendritic cells (DCs), antigen-presenting cells capable of priming naive T cells to specific antigens in an HLA-restricted fashion, have been demonstrated to induce protective T cell-mediated immunity in tumor-bearing animals. We performed this study to test the safety, feasibility, and clinical response of immunizations with in vitro-generated DCs, loaded with an HLA-A2-restricted peptide fragment of the tumor antigen carcinoembryonic antigen (CEA), for the treatment of patients with advanced CEA-expressing malignancies. Cell preparations enriched for autologous DCs were generated from the patients' plastic adherent peripheral blood mononuclear cells in serum-free media supplemented with granulocyte macrophage colony-stimulating factor and interleukin-4. Within the cell preparation, 66% of the cells expressed the phenotype typical for DCs (CD86high, HLA-DRhigh, and CD14low). The DCs were loaded with the CEA peptide CAP-1 and cryopreserved. Groups of three to six patients received four weekly or biweekly i.v. infusions of the CAP-1-loaded DC in escalating dose levels of 1 x 10(7), 3 x 10(7), and 1 x 10(8) cells/dose. A subset of the patients in the last group also received intradermal injections of 1 x 10(6) DCs. There were no toxicities directly referable to the treatments. One patient had a minor response, and one had stable disease. Skin punch biopsy at DC injection sites demonstrated pleomorphic infiltrates in the three patients evaluated. We conclude that it is feasible and safe to generate and administer large numbers of previously cryopreserved DCs loaded with CAP-1 peptide to patients with advanced malignancies.

Adult↗

PubMed1999

Home services or euthanasia: at the heart of the debate.

Home care providers should be concerned about the mounting pressure to control health care expenditures and the reportedly growing public acceptance of assisted suicide and euthanasia. As the aging and disability communities organize politically for the expansion of flexible, consumer-driven, in-home support services, the euthanasia movement has begun to rally its forces behind accelerating death.

Activities of Daily Living↗

PubMed1999

Demographic data for Europe--a review of sources.

Population Trends had provided an overview of European and world demographic issues since its inception in 1975. This article covers the abundant sources of demographic data on all European countries with information on their availability in printed and electronic formats.

Databases, Factual↗

PubMed1998

The effect of two different 18-week walking programmes on aerobic fitness, selected blood lipids and factor XIIa.

Forty-nine previously sedentary or low active individuals aged 40-71 years were allocated to three groups. The long walking group participated in an 18-week walking programme which consisted of walks lasting 20-40 min; the repetitive short walking group completed walks of between 10 and 15 min, up to three times a day, with no less than 120 min between each walk; and the control group maintained their low level of activity. Both walking programmes began at a prescribed 60 min x week(-1), which increased steadily up to 200 min x week(-1) by week 12. During the study, the long walking group walked for an estimated 2514 min (139 min x week(-1)), expending an estimated 67.5 MJ (3.72 MJ x week(-1)) at an estimated 73% of their age-predicted maximum heart rate and 68% of their estimated VO2max. The repetitive short walking group walked for an estimated 2476 min (135 min x week(-1)), expending an estimated 58.5 MJ (3.17 MJ x week(-1)) at an estimated 71% of their age-predicted maximum heart rate and 65% of their estimated VO2max. The results showed a statistically significant reduction in heart rate during a standardized step test (pre- vs post-intervention) in both walking groups, indicating an improvement in aerobic fitness, although the control group showed a higher average heart rate during the post-intervention test, indicating reduced fitness. When compared with the male subjects pre-intervention, the females possessed more favourable levels of high-density lipoprotein (HDL) cholesterol (P< 0.001), apolipoprotein (apo) AI (P < 0.001) and ratios of total cholesterol:HDL cholesterol (P< 0.02) and low-density lipoprotein (LDL) cholesterol: HDL cholesterol (P< 0.02). Compared with the controls post-intervention, the walking groups showed no statistically significant changes in total cholesterol, LDL cholesterol, HDL cholesterol, apo AI, apo AII, apo B, or the ratios of total cholesterol: HDL cholesterol, LDL cholesterol: HDL cholesterol, apo AI: apo B or apo AI: apo AII (P > 0.05). Relative to the walking groups, factor XIIa increased in the control group (P < 0.05). We conclude that, although both walking programmes appeared to improve aerobic fitness, there was no evidence of improvements in the blood lipids or associated apolipoproteins of the walking groups. Further analysis indicated that this apparent lack of change may have been related to the subjects' relatively good pre-intervention blood lipid profiles, which restricted the potential for change. The implications of the observed changes in the coagulation/fibrinolytic factors remain unclear.

Adult↗

PubMed1998

Autosomal dominant hereditary spastic paraparesis with cognitive loss linked to chromosome 2p.

A family initially considered to have 'pure' autosomal dominant hereditary spastic paraparesis (HSP), was found on neuropsychological testing to have evidence of late onset cognitive impairment. This family showed genetic linkage to the SPG4 locus on chromosome 2p previously reported for pure HSP. Of 56 living members, 44 were examined, 30 of whom were > 30 years of age and 12 members were found to be affected with HSP including four asymptomatic cases. One other family member (III-5), aged 62 years, died prior to this study of a 4-year dementing illness. Neuropsychological assessment of 11 affected members and 11 matched, unaffected, family controls showed no significant differences between the two groups. However, the neuropsychological test profile in four of 11 affected members tested (mean age 47.2 years) and one of 11 family controls (mean age 41.5 years) showed global cognitive impairment. The pattern of cognitive dysfunction was the same for all five family members identified and was similar to that found in subcortical dementia. The presence of cognitive impairment appeared to be related to age and not the severity of the paraplegia. Both the severity of the paraplegia and the age of onset (21-60 years) varied considerably in this family.

Adult↗

PubMed1998

Buccal absorption of etomidate from a solid formulation in dogs.

UNLABELLED: Etomidate is typically administered i.v. for the induction of general anesthesia. We believe that oral transmucosal absorption may extend etomidate's use to premedication and conscious sedation. Our objective was to study the oral mucosal absorption kinetics and bioavailability of etomidate in a solid dose form in dogs. A solid dose form containing 50 mg of etomidate in sorbitol for buccal administration was prepared. Each dog was administered both i.v. etomidate and buccal etomidate on separate days. Serum etomidate concentrations after i.v. administration were fit to a two-compartment pharmacokinetic model. The rates at which etomidate enters the systemic circulation via buccal mucosal absorption were calculated from serum concentrations from mucosal and i.v. administrations using model-dependent constrained numerical deconvolution. The apparent permeability coefficient and bioavailability were also determined. The mean (+/- SD) maximal serum etomidate concentration after buccal mucosal absorption from the 50-mg dose unit was 239 +/- 79 ng/mL. The time to reach maximal serum concentration was 12.5 +/- 1.8 min. Peak absorption rate of etomidate into the systemic circulation was 832 +/- 417 microg/min. For all dogs, 90% or more of the absorption via buccal mucosa took place during the period in which the drug was in contact with the mucosa (15 min). The apparent transbuccal mucosal permeability coefficient was 9.1 +/- 4.2 x 10(-4) cm/s, higher than values of any other compounds examined. Bioavailability calculated using the area under the serum etomidate concentration versus time curve method and the deconvolution method was 13.6% +/- 10.7% and 16.6% +/- 7.6%, respectively. In conclusion, etomidate is highly permeable through the canine buccal mucosa. IMPLICATIONS: Etomidate is highly permeable through the canine buccal mucosa. Both the onset and the termination of buccal mucosal absorption of etomidate are rapid, which suggests that titratable delivery of etomidate may be possible by buccal administration.

Absorption↗