SEARCH · PubMed Health

Results for “virtual intervention”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

1,346 records · Page 75Linked to original sources

PubMed2003

Influence of coronary pulsation on volumetric intravascular ultrasound measurements performed without ECG-gating. Validation in vessel segments with minimal disease.

Volumetric analysis of coronary arteries can be performed using intravascular ultrasound (IVUS) images selected at 1 mm intervals without ECG gating. However, there are few data regarding the influence of coronary pulsation on this volumetric analysis. We developed two models of consecutive area measurements consisting of duplicated area measurements from short coronary segments and virtual measurements based on a sine function. These models allowed the re-calculation of volumes using different sets of frames from the same simulated segments. The variability of the volume determinations was evaluated by its percent standard deviation [%SD = (SD/the mean value) x 100]. The relation of the variability to the extent of external elastic membrane (EEM) area change during the cardiac cycle (amplitude) and heart rates (frequency) were examined. In 58 short coronary segments of 15 patients, consecutive IVUS images were measured [%EEM area change: 12.3 +/- 7.7%, heart rate 78 +/- 21 beats/min (bpm)]. In both models, %SD of the volume calculations was directly proportional to the %EEM area change and showed two peaks at heart rates of 60 +/- 2 and 90 +/- 2 bpm. In the model based on actual coronary measurements, the %SD of volume calculations of a segment with 10% EEM area change was 0.7% except for heart rates of 60 +/- 2 and 90 +/- 2 bpm. The variability of a volumetric analysis based upon measuring IVUS images at constant intervals without ECG gating is affected by coronary pulsation, extent of cross-sectional area changes, and heart rate. Despite these limitations, this method is feasible and provides reproducible volume measurements.

Coronary Artery Disease↗

PubMed2006

Coronary plaque composition of nonculprit lesions, assessed by in vivo intracoronary ultrasound radio frequency data analysis, is related to clinical presentation.

BACKGROUND: Identification of subclinical high-risk plaques is potentially important because they may have greater likelihood of rupture and subsequent thrombosis. The purpose of this study was to assess the relationship between plaque composition determined by intravascular ultrasound (IVUS) radio frequency (RF) data analysis and clinical presentation. METHODS: In 55 patients, a nonculprit vessel with < 50% diameter stenosis was studied with IVUS. Tissue maps were reconstructed from RF data using IVUS-Virtual Histology software. RESULTS: Mean percentage of the different plaque components were 0.99% +/- 0.9%, calcium; 68.04% +/- 9.8%, fibrous; 19.31% +/- 7.3%, fibrolipidic; and 9.43% +/- 6.6%, lipid core. Mean lipid core percentage was significantly larger in patients with acute coronary syndrome (ACS) when compared with stable patients (12.26% +/- 7.0% vs 7.40% +/- 5.5%, P = .006). In addition, stable patients showed more fibrotic vessels (70.97% +/- 9.3% vs 63.96% +/- 9.1%, P = .007). There was no significant difference for either mean calcium (1.20% +/- 1.1% vs 0.83% +/- 0.7%, P = .124) or fibrolipidic (20.57% +/- 6.9% vs 18.40% +/- 7.6%, P = .281) percentages in ACS and stable patients, respectively. Vessel area obstruction did not differ between groups (46.49% +/- 10.9% vs 42.83% +/- 11.8%, P = .221). There was a significant, albeit weak, positive correlation between lipid core percentage and stenosis severity as determined by vessel area obstruction (r = 0.34, P = .015). CONCLUSIONS: In this study, plaque characterization of nonculprit vessels using spectral analysis of IVUS RF data analysis was significantly related to clinical presentation. Percentage of lipid core, a feature related to acute coronary events and worse prognosis, was significantly larger in patients with ACS. Conversely, stable patients showed more fibrotic content.

Aged↗

PubMed1997

Effects of crystalloid solutions on circulating lactate concentrations: Part 1. Implications for the proper handling of blood specimens obtained from critically ill patients.

OBJECTIVES: a) To test the hypothesis that circulating lactate concentrations are the same in simultaneously collected arterial and central venous blood specimens; b) to test the hypothesis that even small amounts of crystalloid solutions, which are inadequately "cleared" from these indwelling arterial and venous catheters, can lead to clinically important and misleading changes in the measured lactate values. DESIGN: A prospective, multiexperiment study. SETTING: A critical care research laboratory and a 20-bed intensive care unit (ICU). PATIENTS: Three hundred fifty-five patients. INTERVENTIONS: Blood samples were collected. MEASUREMENTS AND MAIN RESULTS: Experiment 1: Simultaneously collected arterial and central venous blood specimens were obtained on 148 occasions from 48 medical ICU patients receiving no lactated Ringer's solution (RL). Arterial and central venous lactate values were nearly identical in these patients. The correlation between the arterial and central venous lactate concentrations was excellent (r2 = .85; p < .0001) and the agreement between the arterial and central venous lactate concentrations was also excellent (bias and precision = 0.04 mmol/L and +/- 0.38 mmol/L, respectively). Experiment 2: Arterial and mixed venous blood samples were obtained from 100 percutaneous transluminal coronary angioplasty (PTCA) and 75 cardiac surgical patients immediately before the performance of these cardiac procedures. We found the central venous lactate concentrations to be higher than arterial lactate values in the cardiac surgical group, and there was a very poor correlation (r2 = .07) between arterial and central venous lactate values in the cardiac surgical group. The correlation between central venous and arterial lactate concentrations in the PTCA patients was excellent (r2 = .84) and similar to the findings of experiment 1. Since the cardiac surgical patients received RL and the PTCA patients received no RL, we speculated that the intravenous infusion of RL in the cardiac surgical group accounted for these discordant findings. To test this speculation, we performed experiments 3 and 4. Experiment 3: In a large bench study, blood specimens were divided into multiple 1-mL aliquot portions, to which 0.01, 0.05, 0.10, 0.50, or 1.0 mL of various crystalloid solutions, containing or not containing RL, were added. In a volume-dependent and linear manner, solutions containing RL increased the circulating lactate concentration from 10% to > 400% of the baseline lactate value. In a volume-dependent and linear fashion, the non-RL crystalloid solutions decreased the lactate concentration by 0 to 66% of the baseline nondiluted lactate concentration. Experiment 4: In 30 different cardiac surgical patients, we simultaneously obtained central venous and arterial blood specimens. Patients this time received no RL, and catheter lines were adequately cleared (removal > 5 mL) of crystalloid solutions. We found a correlation (r2 = .82; p < .0001) that was virtually identical to the findings of experiment 1 and to the findings in the PTCA group of experiment 2. CONCLUSIONS: a) Arterial and central venous lactate concentrations are similar in hemodynamically stable critically ill patients, b) Even small amounts of RL-containing solutions in catheters used for blood sampling may cause false increases in the circulating lactate concentration. c) Even small amounts of non-RL crystalloid solutions in catheters used for blood sampling may falsely decrease circulating lactate values. d) When blood specimens are drawn from indwelling catheters, all crystalloid solutions must be cleared from the line.

Blood Specimen Collection↗

PubMed2000

Strategies for the physiome project.

The physiome is the quantitative description of the functioning organism in normal and pathophysiological states. The human physiome can be regarded as the virtual human. It is built upon the morphome, the quantitative description of anatomical structure, chemical and biochemical composition, and material properties of an intact organism, including its genome, proteome, cell, tissue, and organ structures up to those of the whole intact being. The Physiome Project is a multicentric integrated program to design, develop, implement, test and document, archive and disseminate quantitative information, and integrative models of the functional behavior of molecules, organelles, cells, tissues, organs, and intact organisms from bacteria to man. A fundamental and major feature of the project is the databasing of experimental observations for retrieval and evaluation. Technologies allowing many groups to work together are being rapidly developed. Internet II will facilitate this immensely. When problems are huge and complex, a particular working group can be expert in only a small part of the overall project. The strategies to be worked out must therefore include how to pull models composed of many submodules together even when the expertise in each is scattered amongst diverse institutions. The technologies of bioinformatics will contribute greatly to this effort. Developing and implementing code for large-scale systems has many problems. Most of the submodules are complex, requiring consideration of spatial and temporal events and processes. Submodules have to be linked to one another in a way that preserves mass balance and gives an accurate representation of variables in nonlinear complex biochemical networks with many signaling and controlling pathways. Microcompartmentalization vitiates the use of simplified model structures. The stiffness of the systems of equations is computationally costly. Faster computation is needed when using models as thinking tools and for iterative data analysis. Perhaps the most serious problem is the current lack of definitive information on kinetics and dynamics of systems, due in part to the almost total lack of databased observations, but also because, though we are nearly drowning in new information being published each day, either the information required for the modeling cannot be found or has never been obtained. "Simple" things like tissue composition, material properties, and mechanical behavior of cells and tissues are not generally available. The development of comprehensive models of biological systems is a key to pharmaceutics and drug design, for the models will become gradually better predictors of the results of interventions, both genomic and pharmaceutic. Good models will be useful in predicting the side effects and long term effects of drugs and toxins, and when the models are really good, to predict where genomic intervention will be effective and where the multiple redundancies in our biological systems will render a proposed intervention useless. The Physiome Project will provide the integrating scientific basis for the Genes to Health initiative, and make physiological genomics a reality applicable to whole organisms, from bacteria to man.

Computer Simulation↗

PubMed2001

Hopkins Teen Central: Assessment of an internet-based support system for children with cystic fibrosis.

UNLABELLED: Support groups are an important therapeutic intervention for patients with chronic debilitating illnesses. Patients who are difficult to assemble in one physical location may benefit from participating in an electronic support group (ESG). ESGs for adolescents have not been evaluated, although studies have shown a benefit to adult ESGs. Our goals were to create a web-based support service for adolescents with cystic fibrosis (CF) and to qualitatively and quantitatively measure the effects that such a support site could have on patients' relationships with the clinic faculty and staff, access to and interaction with peers with CF, and understanding of CF. METHODS: A highly interactive ESG was developed after discussions with a team of CF specialists and patients. Eighteen of 37 teenagers with CF agreed to use this site. Each patient was asked to assess his or her perceived availability of and comfort with the clinic staff and faculty, perceived support available through peers, knowledge about CF, and perceived usefulness of the Internet as a support tool. RESULTS: Participants logged into the site an average of 4 times each month. Teens who owned home computers accessed the site somewhat more frequently than did teens who were provided with home Internet access for the study. Most activity occurred in those sections of the site that described the participants and that allowed them to socialize. Over one half of the participants e-mailed each other at least once a week, with 77% e-mailing peers at least every other week. There was no significant difference in the participants' scores on a quiz about CF at the beginning and the end of the study; however, there was a significant decrease in perceptions about their knowledge about CF. At the conclusion of the study, participants believed that they had more friends who they could relate to than they did at the beginning of the study. Clinic staff noticed an increase in references to peers among the group who were using the site. In addition, 4 of the teens expressed a desire to get together to meet each other as a result of their interactions on the web site. There was no significant change in perceptions about the perceived availability and comfort with the clinic staff and faculty, support available through peers, knowledge about CF, and the usefulness of the Internet as a support environment. Managing the project was extremely easy, with virtually no technical or procedural issues arising during the study. CONCLUSIONS: Teenagers with a chronic disease will actively participate in an ESG. The social and expressive aspects of their involvement with this support group hold much promise.

Adolescent↗

PubMed2005

Association of plaque characterization by intravascular ultrasound virtual histology and arterial remodeling.

Positive remodeling is more often observed in lesions of patients who have acute coronary syndromes or vulnerable (rupture-prone) plaques. However, there are few data that correlate plaque morphology, composition, and arterial remodeling in vivo. We evaluated coronary plaque characterization of lesions with positive remodeling using intravascular ultrasound (IVUS) radiofrequency data analysis. Seventy-seven nonbifurcation native coronary lesions (in 50 patients) were imaged in vivo using 30-MHz IVUS transducers. Lesions were classified into 4 plaque types, fibrous, fibrofatty, dense calcium, and necrotic core, by using processing of the radiofrequency signal validated in vitro. The remodeling index was calculated as the lesion external elastic membrane area divided by the proximal reference external elastic membrane area. Lesions were divided into 2 groups: positive remodeling (remodeling index>1.0, 26 lesions) and intermediate/negative remodeling (remodeling index<or=1.0, 51 lesions). Total plaque volume and the volume of each plaque type were averaged over the length of the lesion. Reference segment plaque compositions were similar. Mean lesion fibrofatty plaque area was significantly larger in lesions with positive remodeling than in lesions with intermediate/negative remodeling (1.2+/-0.7 vs 0.8+/-0.4 mm2, p=0.001; 26.3+/-6.6% vs 19.8+/-5.7%, p<0.001, of total plaque volume). The same results were obtained at the minimum lumen site and in the subgroup of patients who had acute coronary syndromes. Further, there was a linear relation between remodeling index and fibrofatty plaque area (r=0.26, p=0.02). In conclusion, in vivo IVUS radiofrequency data analysis demonstrates that positive remodeling occurs in lesions with more fibrofatty plaque.

Coronary Artery Disease↗

PubMed1996

How rational is the crossmatching of blood in a pediatric emergency department?

OBJECTIVE: To determine if typed and crossmatched blood ordered in a pediatric emergency department (ED) is actually used for transfusion and if some ordering patterns are not cost-effective. DESIGN: Retrospective medical record review. Emergency department records and blood bank logs were reviewed daily to identify patients who had a type and crossmatch (T&C) ordered; inpatient records were then reviewed. A priori diagnostic and patient care categories were determined. Physicians and nurses providing care were unaware of the study. SETTING: An inner-city, tertiary care, pediatric trauma center ED. PATIENTS: A consecutive sample of ED patients who had a T&C ordered from October 1, 1993, through January 31, 1994. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Outcome measures included age, general category of diagnosis, number of units of blood crossmatched and transfused within 7 days, hemoglobin concentration in the ED, surgical procedures in the operating room, and hospital charges for typed and crossmatched blood. For trauma patients, the Pediatric Trauma Score was recorded. The crossmatch-to-transfusion (C/T) ratio was calculated for each diagnostic category (the typical C/T ratio for US hospitals is 2). We calculated a new ratio, the patient-to-transfusion (P/T) ratio, to correct for the transfusion of numerous units of blood in a few patients. RESULTS: Two hundred eighty-two patients had 468 U of blood typed and crossmatched. Fifty-six patients received a total of 110 U of blood. The mean hemoglobin concentration was 81 g/L for patients who received a transfusion and 117 g/L for patients who did not receive a transfusion (P < .001). The C/T ratio for all patients was 4.3. The P/T ratio for all patients was 5.3. Sixty-four surgery patients had 78 U of blood typed and crossmatched; 1 U of blood was transfused to 1 patient, yielding a C/T ratio of 78 and a P/T ratio of 64. Ninety-one units of blood were typed and crossmatched for 38 major trauma patients; 20 U of blood were transfused to 2 patients, 19 U were transfused to 1 patient with a Pediatric Trauma Score of 4, and 1 U was transfused to a patient with a Pediatric Trauma Score of 7. The C/T ratio for major trauma patients was 4.6, and the P/T ratio was 19. Forty-five children with ventriculoperitoneal shunt problems had 51 U of blood typed and crossmatched, but no blood was transfused. Children with sickle-cell disease had a C/T ratio of 2.2 and a P/T ratio of 3.3; those with cancer diagnoses had a C/T ratio of 1.6 and a P/T ratio of 1.3. During the 4-month study period, the hospital charged $84,726 for these T&Cs. The charge for T&Cs never used for transfusion was $65,643 (77.5%). CONCLUSIONS: Most typed and crossmatched units of blood ordered in our pediatric ED were never used for transfusion. The C/T and P/T ratios were high for many diagnostic categories, suggesting inefficient blood ordering and patient management. Transfusions were uncommon in children with the following problems: ventriculoperitoneal shunt malfunction, virtually all surgical diagnoses, cancer with a hemoglobin concentration greater than 105 g/L, and trauma patients with a Pediatric Trauma Score of greater than 7.

Adolescent↗

PubMed2004

Diagnostic value of CT virtual intravascular endoscopy in aortic stent-grafting.

PURPOSE: To investigate the diagnostic value of postprocessing techniques for 3-dimensional (3D) computed tomography (CT), with emphasis on CT virtual intravascular endoscopy (VIE), in patients with abdominal aortic aneurysms (AAA) treated with suprarenal stent-grafts. METHODS: The preprocedural and postprocedural CT datasets from 47 AAA patients (40 men; mean age 75 years, range 61-87) undergoing aortic stent-grafting with suprarenal fixation were examined. The CT datasets were processed to create various 3D reconstructions: shaded surface display (SSD), maximum intensity projection (MIP), and VIE. Three independent radiologists assessed various diagnostic parameters for each 3D reconstruction method and compared them to axial CT images. RESULTS: Scores for VIE reconstructions were inferior to axial CT images in the visualization of normal arterial branches, measurement of the aneurysm diameter and neck length, as well as assessment of vessel patency and presence of endoleaks. VIE was rated superior to axial CT and other 3D imaging methods in visualizing the configuration of stent struts relative to the aortic branch ostia and the number of stent wires crossing the ostia in >80% of cases. CONCLUSIONS: VIE was not found to play a role in most preoperative situations compared to axial CT images. However, VIE provided additional postgrafting information on the 3D relationship of the suprarenal stent struts to the aortic branch ostia (in particular the renal and superior mesenteric arteries). VIE findings might aid clinicians in accurately assessing the effect of suprarenal stent-grafting on the renal arteries.

Aged↗

PubMed2006

[Relationship between high sensitive C-reactive protein and coronary plaque component in patients with acute coronary syndrome: Virtual Histology study].

OBJECTIVES: Elevated circulating C-reactive protein (CRP)is commonly observed in patients with acute coronary syndrome(ACS), suggesting enhanced inflammation in vulnerable plaques. However, few data are available on the relationship between the levels of CRP and the histological composition of coronary plaque. We investigated the relationship between plasma high sensitive CRP level and coronary plaque component with Virtual Histology intravascular ultrasound (VH-IVUS). METHODS: Twenty eight patients with ACS and 37 patients with non-ACS were enrolled in the study. Plasma high sensitve CRP levels were measured before catheterization. A total of 125 lesions (ACS; 24 culprit lesions, 30 non-culprit lesions, non-ACS; 34 culprit lesions, 37 non-culprit lesions)underwent IVUS volumetric investigation, and the volume of plaque and media were calculated. Spectral analysis of IVUS radiofrequency data was performed with VH software, and plaque and media were classified into fibrous, fibro-fatty, dense calcium, and necrotic core elements. RESULTS: Although the plasma high sensitive CRP level in patients with ACS was higher than that in those with non-ACS (0.26 +/- 0.2 vs 0.15 +/- 0.17 mg/dl, p < 0.05), necrotic core volume was not different between the two groups(11.7 +/- 7.3 vs 12.3 +/- 7.2mm3/cm, p = 0.71). There was a positive correlation between high sensitve CRP and necrotic core volume in patients with ACS, not only in culprit lesions (p = 0.0004, r2 = 0.564) but also in non-culprit lesions (p = 0.0008, r2 = 0.473), whereas patients with non-ACS showed no correlations. CONCLUSIONS: IVUS spectral analysis revealed that elevated plasma high sensitve CRP level was correlated with necrotic core volume in patients with ACS, both in culprit and non-culprit lesions, suggesting enhanced vascular inflammation.

Acute Disease↗

PubMed2006

Association of coronary plaque composition and arterial remodelling: a virtual histology analysis by intravascular ultrasound.

BACKGROUND: Conflicting data have been reported about the correlation between plaque composition assessed by virtual histology (VH) and remodelling index (RI). AIM: To evaluate, in a larger patient population, the relationship between plaque morphology obtained by VH and arterial remodelling. METHODS AND RESULTS: VH intravascular ultrasound was performed on 95 non-bifurcation native significant lesions (>75% stenosis) in 85 patients. Positive remodelling (defined as RI > or =1.05) was present in 28 lesions, whereas intermediate/negative remodelling (RI <1.05) was present in 67 lesions. Compared with intermediate/negative remodelling, positive remodelling was associated with an increased frequency of patients with acute coronary syndrome (n = 13 (52%) vs n = 15 (25%); p = 0.017), and with a greater plaque burden (mean (SD) 78.3 (6.3)% vs 73.2 (6.8)%, p = 0.001). At the minimal lumen site, necrotic core was significantly smaller in lesions with positive remodelling (median (interquartile range) 5.0% (2.2-11.0%)) than in lesions with intermediate/negative remodelling (median (interquartile range) 9.0% (4.0-16.0%); p = 0.048). No differences were observed in the rate of thin-cap fibroatheroma or in the presence of multiple necrotic core layers, and there were no statistical differences for fibrous, fibro fatty and dense calcium percent plaque area at the minimum lumen diameter (MLD), or for the entire lesion length between both groups. CONCLUSIONS: In vivo VH analysis shows that lesions with positive remodelling have statistically less necrotic core percent area at the MLD site compared with intermediate/negative remodelling lesions.

Aged↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

PubMed2005

Genotoxicity of environmental agents assessed by the alkaline comet assay.

Generation of DNA damage is considered to be an important initial event in carcinogenesis. A considerable battery of assays exists for the detection of different genotoxic effects of compounds in experimental systems, or for investigations of exposure to genotoxic agents in environmental or occupational settings. Some of the tests may have limited use because of complicated technical setup or because they only are applicable to a few cell types. The single cell gel electrophoresis (comet) assay is technically simple, relatively fast, cheap, and DNA damage can be investigated in virtually all mammalian cell types without requirement for cell culture. The aim of this thesis was to evaluate the comet assay as a genotoxicity test in genetic toxicology of environmental agents, encompassing both experimental animal models and biomonitoring. The comet assay detects strand breaks (SB). The cells are embedded in agarose and lysed, generating nucleus-like structures in the gel (referred to as nucleoids). Following alkaline electrophoresis, the DNA strands migrate toward the anode, and the extent of migration depends on the number of SB in the nucleoid. The migration is visualized and scored in a fluorescence microscope after staining. Broad classes of oxidative DNA damage can be detected as additional SB if nucleoids are incubated with bacterial DNA glycosylase/endonuclease enzymes. Oxidized pyrimidines and purines can be detected by incubation with endonuclease III and formamidopyrimidine DNA glycosylase, respectively. The animal experimental studies indicated that the comet assay was able to detect genotoxic effects of diesel exhaust particles in lung tissue, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced DNA damage in colon epithelial cells and liver tissue, and benzene-induced damage in bone marrow and liver cells. The strength of the comet assay was further outlined by application of repair enzymes, indicating no oxidative DNA base damage following IQ treatment. High levels of oxidative DNA lesions were detected after exposure to benzene or X-ray irradiation. The comet assay did not detect DNA damage in colon or liver following ingestion of diets containing of high contents of animal fat or sucrose, although other indices of DNA damage were found. Determined from the results of a large Japanese study, the discrimination between carcinogens and non-carcinogens appears to be similar between the comet assay and alkaline elution, which also detects SB. This suggests that the comet assay is a reliable genotoxicity test in animal experimental systems. In the biomonitoring studies, we investigated the effect of common exposures and lifestyle factors (rather than effects of known carcinogens) on the level of oxidative DNA damage in mononuclear blood cells of humans. In the first study, based on repeated measurements, it was shown that interindividual variation and seasonal variation were major determinants for the basal level of SB, whereas no effect of age, exercise, or antioxidant intake could be detected. The effect of exercise was further investigated under both normoxic and hypoxic circumstances, showing a strong effect of hypoxia, and only effect of exercise in terms of SB in hypoxia. In a placebo-controlled parallel dietary fruit and vegetable (or the corresponding amount of antioxidants) intervention study, no effects of the level of oxidative DNA damage or sensitivity to hydrogen peroxide were observed. Although this may seem in contrast to other antioxidant intervention studies, a critical literature survey of antioxidant intervention studies on oxidative DNA damage suggested that well-controlled studies tended to show no effect of antioxidant supplementation. In summary, the aggregated data from the publications included in this thesis, and other publications encompassing the comet assay, indicate that the comet assay is a reliable method for detection of DNA damage in tissues of experimental animals. Although not all types of genotoxic exposures should be expected to result in DNA damage in mononuclear blood cells, the comet assay seems to be a valuable tool for detection of genotoxic exposure in humans. The comet assay indicates that DNA damage is abundant in mammalian cells and affected by lifestyle and many environmental exposures, including diet, exercise, hypoxia, and sunlight.

Animals↗

PubMed2004

Differences in the topographical distribution of articular cartilage degeneration between equine metacarpo- and metatarsophalangeal joints.

REASONS FOR PERFORMING STUDY: The equine metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints, although having virtually the same geometrical appearance, differ in the prevalence of joint pathologies, such as osteochondral fragmentation, and in biomechanical behaviour. The recently developed cartilage degeneration index (CDI) technique offers a possibility to assess quantitatively differences in cartilage degeneration between these joints and to compare these with known differences in biomechanics and clinical observations. OBJECTIVES: To compare the topographical distribution of articular cartilage degeneration across the proximal articular surface of the proximal phalanx (P1) in the equine fore- and hindlimb. METHODS: In 24 distal hindlimbs from 24 horses, articular cartilage degeneration of the proximal articular surface of P1 was quantified using the CDI. Overall CDI value (CDI(P1)) and CDI values of 6 areas of interest were determined: the medial dorsal surface (mds), lateral dorsal surface (lds), medial central fovea (mcf), lateral central fovea (lcf), medial plantar surface (mps) and lateral plantar surface (lps). The joints were divided into 4 equally sized groups of increasing CDI(P1) values. From an existing CDI database of MCP joints, 24 joints were selected with matching CDI(P1) values to the MTP joints and CDI values for the same areas of interest were determined. RESULTS: In both the MCP and MTP joints, highest CDI values were determined at the dorsal articular surfaces. Values were not significantly different between fore- and hindlimbs. In contrast to the MCP joint, CDI values at the plantar joint margin were significantly higher compared to CDI values in the central sites in the MTP joint. CDI values for the plantar surfaces of P1 were significantly higher than those for the palmar surfaces in the forelimb in joints with advanced stages of OA; and values for the central regions of P1 were significantly lower in the hindlimb compared with the forelimb in joints with severe OA. CONCLUSIONS: In both fore- and hindlimbs, initial cartilage degeneration started at the dorsal articular margin of P1. There was a major difference in the spread of cartilage degeneration; in the forelimb both the central and palmar parts are about equally involved, whereas in the hindlimb the plantar parts were significantly more and the central parts significantly less involved. These differences can be linked to differences in biomechanical loading reported elsewhere. POTENTIAL RELEVANCE: This study supports the hypothesis that differences in biokinematics between fore- and hindlimbs are associated with differences in the development of cartilage degeneration and other joint pathologies such as osteochondral fragmentation in the MCP and MTP joints. This information is indispensable for a better understanding of the dynamic nature and progression of these joint disorders and may be of help when monitoring the effects of therapeutic interventions and preventative measures.

Animals↗

PubMed2005

In vivo intravascular ultrasound-derived thin-cap fibroatheroma detection using ultrasound radiofrequency data analysis.

OBJECTIVES: The purpose of this study was to assess the prevalence of intravascular ultrasound (IVUS)-derived thin-cap fibroatheroma (IDTCFA) and its relationship with the clinical presentation using spectral analysis of IVUS radiofrequency data (IVUS-Virtual Histology [IVUS-VH]). BACKGROUND: Thin-cap fibroatheroma lesions are the most prevalent substrate of plaque rupture. METHODS: In 55 patients, a non-culprit, non-obstructive (<50%) lesion was investigated with IVUS-VH. We classified IDTCFA lesions as focal, necrotic core-rich (> or =10% of the cross-sectional area) plaques being in contact with the lumen; IDTCFA definition required a percent atheroma volume (PAV) > or =40%. RESULTS: Acute coronary syndrome (ACS) (n = 23) patients presented a significantly higher prevalence of IDTCFA than stable (n = 32) patients (3.0 [interquartile range (IQR) 0.0 to 5.0] vs. 1.0 [IQR 0.0 to 2.8], p = 0.018). No relation was found between patient's characteristics such as gender (p = 0.917), diabetes (p = 0.217), smoking (p = 0.904), hypercholesterolemia (p = 0.663), hypertension (p = 0.251), or family history of coronary heart disease (p = 0.136) and the presence of IDTCFA. A clear clustering pattern was seen along the coronaries, with 35 (35.4%), 31 (31.3%), 19 (19.2%), and 14 (14.1%) IDTCFAs in the first 10 mm, 11 to 20 mm, 21 to 30 mm, and > or =31 mm segments, respectively, p = 0.008. Finally, we compared the severity (mean PAV 56.9 +/- 7.4 vs. 54.8 +/- 6.0, p = 0.343) and the composition (mean percent necrotic core 19.7 +/- 4.1 vs. 18.1 +/- 3.0, p = 0.205) of IDTCFAs between stable and ACS patients, and no significant differences were found. CONCLUSIONS: In this in vivo study, IVUS-VH identified IDTCFA as a more prevalent finding in ACS than in stable angina patients.

Aged↗