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Biomedical subjects

Michael B Rubens

Publications and source records attributed to Michael B Rubens.

12 recordsLinked to original sources

Asbestos-induced and smoking-related disease: apportioning pulmonary function deficit by using thin-section CT.

PURPOSE: To retrospectively correlate the extent of individual diseases seen at thin-section computed tomography (CT) with pulmonary function in an initial group of patients with asbestos-related parenchymal disease (asbestosis) and to test these findings in a subsequent group of patients whose CT scans were retrospectively identified. MATERIALS AND METHODS: This retrospective study had Institutional Review Board approval; informed consent was not required. The study included 133 individuals who had been exposed to asbestos. In the initial study group (81 patients; 79 men, two women; median age, 67 years), two observers used a CT scoring system to quantify the extent of pulmonary fibrosis, diffuse pleural thickening, small-airways disease, and emphysema. Multivariate equations were formulated by using independent CT variables to predict changes in total lung capacity (TLC) and carbon monoxide diffusing capacity (Dlco). The validity of these equations was then tested in a subsequent group of patients (52 patients; all men; median age, 60 years). RESULTS: At thin-section CT, the extent of asbestos-induced pleuropulmonary disease and emphysema correlated significantly with physiologic impairment (P<.001). Combined CT variables predicted 58% and 57% of the variability in TLC and Dlco, respectively, despite considerable variation in the proportion of coexisting pathologic conditions. When predictive equations with CT variables derived from the initial study group were applied to the subsequent study group, predicted TLC (rho=0.75, P<.001) and Dlco (rho=0.64, P<.001) correlated strongly with measured values. CONCLUSION: The proposed CT system provides a semiquantitative method for assessing the relative contribution of asbestos-induced pleuropulmonary disease and smoking-related emphysema to functional impairment.

Aged↗

Three-dimensional in vivo characterization of calcification in native valves and in Freestyle versus homograft aortic valves.

OBJECTIVE: This article describes a novel interactive method for quantitative evaluation of calcium deposits in the aortic valve by means of electron beam tomography data fusion technique. METHODS: The technique relied on the use of hierarchic 3-dimensional free-form volume registration with fast global optimization between normally acquired and contrast-enhanced electron beam tomographic volume. A total of 66 contrast-enhanced electron beam tomographic scans of the aortic root were performed in 27 patients, 10 with native aortic valve disease (group A) and 17 from a prospective randomized trial of aortic root replacement (group B, 9 Freestyle grafts [Medtronic, Inc, Minneapolis, Minn] and 8 homografts). To validate the in vivo electron beam tomographic measurements, 5 patients from group A underwent electron beam tomographic scans before the operation and then had their own valves, explanted at the time of surgery, analyzed for calcium quantification by ex vivo electron beam tomography. RESULTS: In group A, the mean (+/- SE) calcification score was 6560 +/- 2388, which correlated with peak gradients measured at echocardiography ( r = 0.93, P = .02). In group B, the mean (+/- SE) calcification score was 168 +/- 27, showing a tendency toward a lower calcification for Freestyle valves than for homografts at 2 years after implantation ( P = .052). A mean variability of 6% was found between in vivo electron beam tomographic scores of calcification and those measured on valve specimens after explantation. CONCLUSION: We describe a novel method to characterize the degree and location of calcification in both native valves and postoperative valve implants. The technique may be useful in the management of patients with aortic valve disease and has potential as a screening tool for high-risk patients to diagnose early valve calcification and possibly institute corrective measures.

Aged↗

Asbestosis and idiopathic pulmonary fibrosis: comparison of thin-section CT features.

PURPOSE: To identify differences, if any, in thin-section computed tomographic (CT) features between asbestosis and idiopathic pulmonary fibrosis (IPF) and to test the findings in a subset of histopathologically proved cases of usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). MATERIALS AND METHODS: Consecutive patients with a diagnosis of IPF (n = 212) or asbestosis (n = 74) were included. The relationships derived from the initial comparison were tested in a separate group of biopsy-proved UIP (n = 30) and NSIP (n = 23) cases. Two observers independently scored thin-section CT images for extent, distribution, and coarseness of fibrosis; proportion of ground-glass opacification; severity of traction bronchiectasis; and extent of emphysema. RESULTS: After controlling for extent of fibrosis, patients with asbestosis had coarser fibrosis than those with IPF (odds ratio, 1.52; 95% CI: 1.25, 1.84; P <.001). Compared with the biopsy-proved cases, the asbestosis cases involved coarser fibrosis (after controlling for disease extent) than the NSIP cases (odds ratio, 2.48; 95% CI: 1.49, 4.11; P <.001) but fibrosis similar to that in the UIP cases. A basal and subpleural distribution of disease was usual in all subgroups but significantly more prevalent (P, <.01 to.001) with asbestosis than with UIP or NSIP. CONCLUSION: The thin-section CT pattern of asbestosis closely resembles that of biopsy-proved UIP and differs markedly from that of biopsy-proved NSIP.

Asbestosis↗

Idiopathic pulmonary fibrosis: a composite physiologic index derived from disease extent observed by computed tomography.

In idiopathic pulmonary fibrosis, the quantitation of disease severity using pulmonary function tests is often confounded by emphysema. We have identified the composite physiologic index (CPI) most closely reflecting the morphologic extent of pulmonary fibrosis. Consecutive patients with a clinical/computed tomography (CT) diagnosis of idiopathic pulmonary fibrosis (n = 212) were divided into group I (n = 106) and group II (n = 106). The CPI was derived in group I (by fitting pulmonary function tests against disease extent on CT) and was tested in Group II. The formula for the CPI was as follows: extent of disease on CT = 91.0 - (0.65 x percent predicted diffusing capacity for carbon monoxide [DLCO]) - (0.53 x percent predicted FVC) + (0.34 x percent predicted FEV1). In group II, the CPI correlated more strongly with disease extent on CT (r2 = 0.51) than the individual pulmonary function test (DLCO the highest value, r2 = 0.38). A subanalysis demonstrated that the better fit of the CPI was ascribable to a correction of the confounding effects of emphysema. Mortality was predicted more accurately by the CPI than by a pulmonary function test in all clinical subgroups, including a separate cohort of 36 patients with histologically proven usual interstitial pneumonia (CPI, p < 0.0005; FVC, p = 0.002; PO2, p = 0.002). In conclusion, a new CPI, derived against CT and validated using split sample testing, is a more accurate prognostic determinant in usual interstitial pneumonia than an individual pulmonary function test.

Aged↗

Traction bronchiectasis in cryptogenic fibrosing alveolitis: associated computed tomographic features and physiological significance.

Our objective was to evaluate the associated CT features and physiological consequences of traction bronchiectasis in patients with cryptogenic fibrosing alveolitis (CFA). The CT scans of 212 patients with CFA (158 men, 54 women; mean age 62.2+/-10.6 years) were evaluated independently by two observers. The extent of fibrosis, the proportions of a reticular pattern and ground-glass opacification and the extent of emphysema were scored at five levels. The predominant CT pattern, coarseness of a reticular pattern and severity of traction bronchiectasis were graded semiquantitatively. Physiological indices were correlated with CT features. There was traction bronchiectasis on CT in 202 of 212 (95%) patients. Increasingly severe traction bronchiectasis was independently associated with increasingly extensive CFA ( p<0.0005), a coarser reticular pattern ( p<0.001), a lower proportion of ground-glass opacification ( p<0.005) and less extensive emphysema ( p<0.0005). Increasingly severe traction bronchiectasis was independently related to depression of DL(CO) ( p<0.005), FVC ( p=0.02) and pO(2) ( p<0.0005), but not indices of air-flow obstruction. In CFA, traction bronchiectasis increases with more extensive disease, a lower proportion of ground-glass opacification and a coarser reticular pattern, but it decreases with concurrent emphysema. Increasingly severe traction bronchiectasis is associated with additional physiological impairment for a given extent of pulmonary fibrosis and emphysema.

Bronchiectasis↗

Activated factor XII levels and factor XII 46C>T genotype in relation to coronary artery calcification in patients with type 1 diabetes and healthy subjects.

The relationship of activated factor XII (FXIIa) and FXII 46C>T genotype to coronary atherosclerosis and endothelial function was examined in 192 randomly sampled subjects from the general population and 190 type 1 diabetic subjects (mean age 38+/-4 years). Coronary artery calcification (CAC) was measured using Electron beam CT. von Willebrand factor (vWF), a marker of endothelial function, and FXIIa were measured by ELISA. Endothelial nitric oxide production was quantified as the forearm blood flow response to intra-brachial infusion of bradykinin and N(G) monomethyl-L-arginine (L-NMMA). A higher FXIIa was independently associated with higher triglycerides (P<0.001), BMI (P=0.001), alcohol consumption (P=0.003) and vWF (P<0.001) in non-diabetic subjects and with insulin dose (P=0.009), total cholesterol (P=0.02) and alcohol (P<0.001) in diabetic subjects. Diabetic subjects had lower FXIIa (1.55 ng/ml) than non-diabetic subjects (1.92 ng/ml, P<0.001). Higher FXIIa was associated with lower response to bradykinin (P=0.048) and to L-NMMA (P=0.029). FXIIa was positively associated with CAC (odds ratio=1.57 for every 1 ng/ml higher FXIIa, P=0.005) but not independently of other risk factors (odds ratio=1.1 on adjustment). 46C>T genotype explained 18% of the variance in FXIIa (P<0.001) but was not associated with CAC (P=0.6). We conclude that plasma FXIIa is under strong genetic control but also reflects plasma triglycerides and endothelial activation or dysfunction. FXIIa appears unlikely to be directly atherogenic but may be a useful marker of coronary atherosclerosis because of its association with these other factors. Type 1 diabetes is associated with lower levels of FXIIa despite a greater prevalence of atherosclerosis.

Adult↗

Coronary calcification and predicted risk of coronary heart disease in asymptomatic men with hypercholesterolaemia.

OBJECTIVE: To document the relationship between coronary calcification and coronary risk assessed clinically in asymptomatic patients with hypercholesterolaemia. DESIGN: Prospective observational study. SETTING: Health screening clinic. PATIENTS: A total of 286 asymptomatic men aged 45-64 with plasma cholesterol >or= 6.5 mmol/l. INTERVENTIONS: Electron beam computed tomography to measure coronary calcium score. MAIN OUTCOME MEASURES: The Framingham equation was used to separate subjects into groups with either low 10-year risk of coronary artery disease ( or= 20%). Coronary calcium score was assessed in each group. RESULTS: The mean log calcium score was significantly higher in the 97 high-risk men than in the 189 low-risk men (1.58 +/- 0.84 versus 1.00 +/- 0.85, < 0.001). Arithmetic means (158 versus 55), and the proportion with a score > 400 (11% versus 2%, p < 0.01) were also greater. However, 27% of the high-risk group had a low calcium score ( or= 20% in 10 years have minimal coronary calcification. They may therefore represent a subset at lower risk of disease. However, uncertainties about the predictive power of coronary calcification for coronary events must be resolved before electron beam computed tomography can be used to select high-risk patients for primary prevention.

Age Factors↗

Thin-section CT in obstructive pulmonary disease: discriminatory value.

PURPOSE: To use thin-section computed tomography (CT) to distinguish between causes of obstructive pulmonary disease, to determine which distinctions give rise to diagnostic imprecision, and to identify the most useful CT features. MATERIALS AND METHODS: Thin-section CT scans of 105 patients with obstructive pulmonary disease (asthma, n = 35; centrilobular emphysema, n = 30; panlobular emphysema, n = 21; and obliterative bronchiolitis, n = 19) and 33 healthy subjects were assessed independently by two observers. The most likely diagnosis and a confidence rating were assigned. Individual thin-section CT features were recorded. Accuracy, sensitivity, specificity, negative predictive value, and positive predictive value for first-choice diagnoses were calculated. The prevalence of CT features between pairs of conditions was compared with the chi(2) or Fisher exact test as appropriate. RESULTS: A correct first-choice diagnosis was made in 199 of 276 (72%) observations. A correct first-choice diagnosis was made in 35 of 38 (92%) observations in patients with obliterative bronchiolitis, in 53 of 60 (88%) observations in patients with centrilobular emphysema, in 53 of 66 (80%) observations in healthy subjects, in 37 of 70 (53%) observations in patients with asthma, and in 20 of 42 (48%) observations in patients with panlobular emphysema. The major sources of diagnostic inaccuracy were differentiation between panlobular and centrilobular emphysema, asthma and normality, and asthma and obliterative bronchiolitis. There were significant increases in prevalence of (a) bronchial wall thickening and vascular attenuation in patients with asthma when compared with healthy subjects and (b) vascular attenuation and decreased attenuation in patients with obliterative bronchiolitis when compared with patients with asthma (P <.001). CONCLUSION: CT helps to distinguish diseases that cause airflow obstruction. Thin-section CT is particularly accurate in the identification of obliterative bronchiolitis.

Adolescent↗

C-reactive protein in type 1 diabetes and its relationship to coronary artery calcification.

OBJECTIVE: In 196 type 1 diabetic subjects and 195 nondiabetic subjects aged 30-55 years, we examined whether C-reactive protein (CRP) is elevated in diabetes and whether CRP is associated with coronary artery calcification (CAC). RESEARCH DESIGN AND METHODS: CRP was measured with a highly sensitive immunoassay. CAC was measured using electron beam computed tomography. RESULTS: CRP was elevated in diabetic women compared with nondiabetic women (median 1.62 vs. 0.85 mg/l, P < 0.001) independently of other factors, but was similar in diabetic and nondiabetic men (median 0.82 vs. 0.81 mg/l). Insulin dose per day was positively correlated with CRP in diabetic women (Spearman's rho = 0.36, P = 0.0003) but much less so in men (rho = 0.16, P = 0.09). Being in the top tertile for CRP was associated with CAC in diabetic and nondiabetic men even after adjustment for other risk factors (adjusted odds ratio [OR] = 4.6 and 4.3, respectively, P = 0.02 for both). In nondiabetic women, being in the top tertile for CRP was associated with CAC (OR 3.1, P = 0.04), but not independently of BMI (OR = 1 after adjustment). Among diabetic women the association was not significant even before adjustment for BMI (OR = 2.6, P = 0.07). CONCLUSIONS: Elevated CRP in diabetic women might reflect a particular sensitivity to insulin levels or might reflect insulin resistance. In general, CRP is an important marker of subclinical atherosclerosis, but the clinical significance of elevated CRP in diabetic women needs to be addressed in prospective studies, since CRP was not clearly associated with CAC in this group.

Adult↗

In-vitro verification of the electron beam tomography method for measurement of heart valve calcification.

BACKGROUND AND AIM OF THE STUDY: Electron beam tomography (EBT) has been used previously to study aortic root wall and leaflet calcification. However, the sensitivity of this method must be validated by comparing EBT findings with calcification in the cusps as determined using other techniques. An in-vitro study was designed to examine the correlation between EBT scores of calcification, visual observations, traditional X-radiography, dual-energy X-ray analysis (DEXA) and atomic absorption spectroscopy (AAS). METHODS: Seven commercial and experimental pericardial valves were implanted in the mitral position in juvenile sheep for up to 20 weeks. Valves were examined thoroughly upon explantation and traditional x-radiographs were taken using standard techniques and ranked in increasing order of calcification. A calcification score in Hounsfield Units (HU) and a calcified volume score in mm3 were calculated for each valve by EBT. Calcium content was then calculated by means of DEXA and AAS. RESULTS: Calcification scores ranged from 1.03 to 538.93 HU, and calcified volume scores from 6.18 to 1804.6 mm3. Correlation analysis showed a good agreement between the physical observations, in-vitro traditional X-radiography and both the calcification score and calcified volume score. EBT measurements were highly correlated with the DEXA examinations (r = 0.98, p = 0.0001 versus calcification score; and r = 0.97, p = 0.0003 versus calcified volume score) and AAS analyses (r = 0.98, p = 0.0001 versus calcification score; and r = 0.99, p = 0.0000 versus calcified volume score). CONCLUSION: These preliminary results indicate a good correlation between the physical observations of calcification, X-radiographic observations, DEXA, AAS analyses and EBT measures of calcification.

Absorptiometry, Photon↗