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1.
J Breath Res ; 5(1): 016004, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21378437

ABSTRACT

Several factors contribute to the variability observed among repeated measurements of breath alcohol concentration. Identifying these factors and the magnitude of their contribution is the focus of this study. Large breath alcohol data sets consisting of duplicate test results from drivers arrested for driving while intoxicated were obtained from four jurisdictions: Sweden, Alabama, New Jersey and Washington State. The absolute difference between duplicate results were fitted to a multivariate linear regression model which included the following predictor variables: mean breath alcohol concentration, absolute exhalation time difference between repeated measurements, absolute exhalation volume difference, gender and age. In all data sets considered here, the breath alcohol concentration was the most statistically and practically significant predictor of absolute difference between the duplicate results. The next two most important predictors to enter models for all jurisdictions were exhalation volume difference and exhalation time difference. The maximum multivariate R² for any jurisdiction, however, was only 0.24, suggesting that other factors not considered here may be of importance. Two predictors over which the subject would have some influence included exhalation time and volume. When these were set at values expected to have maximum impact, the effect on duplicate test differences was very small, 0.008 g/210 L or less in all jurisdictions, indicating that subject manipulation of exhalation time and volume would have at most a very small systematic effect on estimated breath alcohol concentration. This study presents multivariate models useful for identifying the impact of five variables that may influence breath test variability.


Subject(s)
Breath Tests/methods , Ethanol/analysis , Exhalation , Forensic Medicine/methods , Substance Abuse Detection/methods , Substance Abuse Detection/statistics & numerical data , Adult , Age Distribution , Alabama , Automobile Driving , Female , Humans , Male , Models, Theoretical , New Jersey , Reproducibility of Results , Sex Distribution , Sweden , Time Factors , Washington
2.
AJNR Am J Neuroradiol ; 31(6): 1068-75, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20093315

ABSTRACT

BACKGROUND AND PURPOSE: The presence of IPH and/or FCR in the carotid atherosclerotic plaque indicates a high-risk lesion. The aim of this multicenter cross-sectional study was to establish the characteristics of lesions that may precede IPH and/or FCR. We further sought to construct a CAS that stratifies carotid disease severity. MATERIALS AND METHODS: Three hundred forty-four individuals from 4 imaging centers with 16%-99% carotid stenosis by duplex sonography underwent carotid MR imaging. In approximately 60% of the study sample (training group), multivariate analysis was used to determine factors associated with IPH and FCR. Statistically significant parameters identified during multivariate analysis were used to construct CAS. CAS was then applied to the remaining arteries (40%, test group), and the accuracy of classification for determining the presence versus absence of IPH or, separately, FCR was determined by ROC analysis and calculation of the AUC. RESULTS: The maximum proportion of the arterial wall occupied by the LRNC was the strongest predictor of IPH (P < .001) and FCR (P < .001) during multivariate analysis of the training group. The subsequently derived CAS applied to the test group was an accurate classifier of IPH (AUC = 0.91) and FCR (AUC = 0.93). Compared with MRA stenosis, CAS was a stronger classifier of both IPH and FCR. CONCLUSIONS: LRNC quantification may be an effective complementary strategy to stenosis for classifying carotid atherosclerotic disease severity. CAS forms the foundation for a simple imaging-based risk-stratification system in the carotid artery to classify severity of atherosclerotic disease.


Subject(s)
Carotid Arteries/pathology , Carotid Artery Diseases/epidemiology , Carotid Artery Diseases/pathology , Magnetic Resonance Imaging , Severity of Illness Index , Aged , Carotid Arteries/diagnostic imaging , Carotid Artery Diseases/diagnostic imaging , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Multivariate Analysis , Prevalence , ROC Curve , Risk Factors , Ultrasonography, Doppler, Duplex
3.
AJNR Am J Neuroradiol ; 31(3): 487-93, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19833801

ABSTRACT

BACKGROUND AND PURPOSE: Surface disruption, either ulceration or fibrous cap rupture, has been identified as a key feature of the unstable atherosclerotic plaque. In this prospective observational study, we sought to determine the characteristics of the carotid lesion that predict the development of new surface disruption. MATERIALS AND METHODS: One hundred eight asymptomatic individuals with 50%-79% carotid stenosis underwent carotid MR imaging at baseline and at 3 years. Multicontrast imaging criteria were used to determine the presence or absence of calcification, LRNC, intraplaque hemorrhage, and surface disruption. Volume measurements of plaque morphology and the LRNC and calcification, when present, were collected. RESULTS: At baseline, 21.3% (23/108) of participants were identified with a surface disruption. After 3 years, 9 (10.6%) of the remaining 85 individuals without disruption at baseline developed a new surface disruption during follow-up. Among all baseline variables associated with new surface disruption during regression analysis, the proportion of wall volume occupied by the LRNC (percentage LRNC volume; OR per 5% increase, 2.6; 95% CI, 1.5-4.6) was the strongest classifier (AUC = 0.95) during ROC analysis. New surface disruption was associated with a significant increase in percentage LRNC volume (1.7 +/- 2.0% per year, P = .035). CONCLUSIONS: This prospective investigation of asymptomatic individuals with 50%-79% stenosis provides compelling evidence that LRNC size may govern the risk of future surface disruption. Identification of carotid plaques in danger of developing new surface disruption may prove clinically valuable for preventing the transition from stable to unstable atherosclerotic disease.


Subject(s)
Calcinosis/pathology , Carotid Arteries/pathology , Carotid Stenosis/pathology , Magnetic Resonance Imaging , Severity of Illness Index , Adult , Aged , Aged, 80 and over , Calcinosis/epidemiology , Carotid Stenosis/epidemiology , Cerebral Hemorrhage/epidemiology , Cerebral Hemorrhage/pathology , Disease Progression , Female , Follow-Up Studies , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , ROC Curve , Risk Factors
4.
Vet Ther ; 9(2): 111-21, 2008.
Article in English | MEDLINE | ID: mdl-18597249

ABSTRACT

The safety of using otic formulations is often of concern for practitioners and pet owners alike, with "safe" in this context meaning no adrenocortical suppression. This study evaluated the effect of four glucocorticoid-containing otic formulations on plasma cortisol concentrations, measured by corticotropin stimulation testing (plasma cortisol concentrations before and after corticotropin injection), in dogs presented with otitis externa. Dexamethasone tended to have larger adrenocortical suppression compared with the other three formulations (betamethasone, triamcinolone, and mometasone), but the difference was not statistically significant. The largest difference among the four drugs was observed between dexamethasone and betamethasone (P=.09).


Subject(s)
Adrenal Glands/drug effects , Anti-Inflammatory Agents/therapeutic use , Dog Diseases/drug therapy , Glucocorticoids/therapeutic use , Otitis Externa/veterinary , Adrenal Glands/immunology , Animals , Anti-Inflammatory Agents/adverse effects , Betamethasone/adverse effects , Betamethasone/therapeutic use , Dexamethasone/adverse effects , Dexamethasone/therapeutic use , Dogs , Female , Glucocorticoids/adverse effects , Hydrocortisone/blood , Male , Mometasone Furoate , Otitis Externa/drug therapy , Pregnadienediols/adverse effects , Pregnadienediols/therapeutic use , Safety , Treatment Outcome , Triamcinolone/adverse effects , Triamcinolone/therapeutic use
5.
Arterioscler Thromb Vasc Biol ; 25(3): 611-6, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15653565

ABSTRACT

OBJECTIVE: Ethnicity-based research may identify new clues to the pathogenesis of atherosclerotic disease. Therefore, we sought to determine whether carotid lesions differ between 20 Chinese and 20 Caucasian Americans by MRI. METHODS AND RESULTS: Inclusion criteria were >50% stenosis as measured by duplex ultrasound and recent symptoms attributed to carotid artery disease. The patients were imaged in 2 centers (Beijing, China and Seattle, Wash) using a standardized protocol. Both carotid arteries were reviewed quantitatively (lumen, wall, outer wall, tissue components) and morphologically (lesion types, fibrous cap status). Significant differences between the Chinese and Americans were found for the mean size of the lipid/necrotic core (13.6 versus 7.8 mm2; P=0.002), percentage of slices with calcified type VII lesions (1.6 versus 12.4%; P=0.03), and percentage of slices with early type III lesions (19.3 versus 9.3%; P=0.02). Furthermore, the mean outer wall area in the common carotid artery was larger in the Chinese population (P=0.007). CONCLUSIONS: This pilot study suggests that composition and morphology of atherosclerotic lesions in symptomatic carotid disease differ between ethno-racial groups. Quantitative MRI-based review of carotid atherosclerosis comparing plaque morphology and composition between ethno-racial groups is feasible, and future MRI studies may improve our understanding of the pathophysiology of this disease.


Subject(s)
Asian People/statistics & numerical data , Carotid Artery Diseases/ethnology , Carotid Artery Diseases/pathology , Magnetic Resonance Imaging , White People/statistics & numerical data , Aged , Aged, 80 and over , Carotid Artery, Common/pathology , China/epidemiology , Female , Humans , Magnetic Resonance Imaging/standards , Male , Middle Aged , Phantoms, Imaging , Pilot Projects , Reproducibility of Results , Risk Factors , United States/epidemiology
6.
Arterioscler Thromb Vasc Biol ; 25(1): 234-9, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15528475

ABSTRACT

OBJECTIVE: This study evaluates the ability of MRI to quantify all major carotid atherosclerotic plaque components in vivo. METHODS AND RESULTS: Thirty-one subjects scheduled for carotid endarterectomy were imaged with a 1.5T scanner using time-of-flight-, T1-, proton density-, and T2-weighted images. A total of 214 MR imaging locations were matched to corresponding histology sections. For MRI and histology, area measurements of the major plaque components such as lipid-rich/necrotic core (LR/NC), calcification, loose matrix, and dense (fibrous) tissue were recorded as percentages of the total wall area. Intraclass correlation coefficients (ICCs) were computed to determine intrareader and inter-reader reproducibility. MRI measurements of plaque composition were statistically equivalent to those of histology for the LR/NC (23.7 versus 20.3%; P=0.1), loose matrix (5.1 versus 6.3%; P=0.1), and dense (fibrous) tissue (66.3% versus 64%; P=0.4). Calcification differed significantly when measured as a percentage of wall area (9.4 versus 5%; P<0.001). Intrareader and inter-reader reproducibility was good to excellent for all tissue components, with ICCs ranging from 0.73 to 0.95. CONCLUSIONS: MRI-based tissue quantification is accurate and reproducible. This application can be used in therapeutic clinical trials and in prospective longitudinal studies to examine carotid atherosclerotic plaque progression and regression.


Subject(s)
Carotid Artery Diseases/pathology , Magnetic Resonance Imaging/methods , Aged , Female , Humans , Male , Reproducibility of Results , Sensitivity and Specificity
7.
Int Clin Psychopharmacol ; 17(6): 281-5, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12409681

ABSTRACT

Although early antidepressant clinical trials simply relied on a clinician's judgment as to whether a depressed patient clinically improved or not, the Hamilton Depression (HAM-D) rating scale has become the 'gold standard' to assess the efficacy of new antidepressants. The alternative Montgomery-Asberg Depression Rating Scale (MADRS) has not achieved general acceptance. However, its ease of use warrants evaluation as to whether it is comparable to HAM-D in its sensitivity in detecting antidepressant-placebo differences in antidepressant clinical trials. A retrospective chart review was performed on the records of 208 depressed adult patients that participated in eight randomized, placebo-controlled, double-blind antidepressant clinical trials at the Northwest Clinical Research Center between 1996 and 2000. We compared the effect sizes of the HAM-D, MADRS and Clinical Impressions Rating Scale (CGI-S for severity and CGI-I for improvement) for patients assigned to placebo or an established antidepressant. The effect size (measured as the mean change in rating with antidepressants minus the mean change for placebo divided by the pooled SD of change, adjusted for age, gender and initial scores) was 0.49 with MADRS, 0.53 with HAM-D, 0.55 with CGI-S and 0.59 with CGI-I. The four rating scales had similar effect sizes regardless of the type of antidepressant evaluated. These data suggest that MADRS is as sensitive an instrument as HAM-D for detecting antidepressant efficacy in clinical trials. Thus, MADRS may be a desirable tool in large-scale, pivotal antidepressant clinical trials.


Subject(s)
Antidepressive Agents/pharmacology , Depressive Disorder/drug therapy , Depressive Disorder/psychology , Psychiatric Status Rating Scales/standards , Adolescent , Adult , Aged , Aged, 80 and over , Double-Blind Method , Female , Humans , Male , Middle Aged , Placebos , Retrospective Studies , Sensitivity and Specificity , Treatment Outcome
8.
Anesthesiology ; 95(6): 1414-21, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11748400

ABSTRACT

BACKGROUND: Perfluorocarbon (PFC) liquids are known to improve gas exchange and pulmonary function in various models of acute respiratory failure. Vaporization has been recently reported as a new method of delivering PFC to the lung. Our aim was to study the effect of PFC vapor on the ventilation/perfusion (VA/Q) matching and relative pulmonary blood flow (Qrel) distribution. METHODS: In nine sheep, lung injury was induced using oleic acid. Four sheep were treated with vaporized perfluorohexane (PFX) for 30 min, whereas the remaining sheep served as control animals. Vaporization was achieved using a modified isoflurane vaporizer. The animals were studied for 90 min after vaporization. VA/Q distributions were estimated using the multiple inert gas elimination technique. Change in Qrel distribution was assessed using fluorescent-labeled microspheres. RESULTS: Treatment with PFX vapor improved oxygenation significantly and led to significantly lower shunt values (P < 0.05, repeated-measures analysis of covariance). Analysis of the multiple inert gas elimination technique data showed that animals treated with PFX vapor demonstrated a higher VA/Q heterogeneity than the control animals (P < 0.05, repeated-measures analysis of covariance). Microsphere data showed a redistribution of Qrel attributable to oleic acid injury. Qrel shifted from areas that were initially high-flow to areas that were initially low-flow, with no difference in redistribution between the groups. After established injury, Qrel was redistributed to the nondependent lung areas in control animals, whereas Qrel distribution did not change in treatment animals. CONCLUSION: In oleic acid lung injury, treatment with PFX vapor improves gas exchange by increasing VA/Q heterogeneity in the whole lung without a significant change in gravitational gradient.


Subject(s)
Fluorocarbons/pharmacology , Pulmonary Circulation/drug effects , Respiratory Distress Syndrome/physiopathology , Algorithms , Animals , Hemodynamics/drug effects , Hemodynamics/physiology , Noble Gases , Oleic Acid , Positive-Pressure Respiration , Pulmonary Gas Exchange , Respiration, Artificial , Respiratory Distress Syndrome/chemically induced , Sheep , Ventilation-Perfusion Ratio/drug effects
9.
Vasc Surg ; 35(2): 85-93, 2001.
Article in English | MEDLINE | ID: mdl-11668375

ABSTRACT

The purpose of this study was to investigate changes in blood pressure and renal function after percutaneous renal artery balloon angioplasty in hypertensive patients with atherosclerotic renal artery stenosis. Renal artery lesions were assessed by duplex ultrasound before and after renal artery balloon angioplasty. Renal arteries were classified as normal, < 60% stenosis, > or =60% stenosis, and occluded according to previously validated duplex criteria. Data regarding risk factors for atherosclerosis and years of hypertension were collected. Systolic and diastolic blood pressure, creatinine, and number of medications were obtained before and after intervention. The immediate technical outcome of renal artery angioplasty was classified based on the arteriographic result as follows: success (residual stenosis < or =30%), partial success (residual stenosis 31-50%), or unsuccessful (residual stenosis > 50%). For bilateral procedures, success required both renal arteries to be classified as technical successes; a technical success on one side only was classified as partial success. The blood pressure response to intervention was classified as follows: cure (diastolic blood pressure < or =95 mm Hg on no medications), improved (control of blood pressure with a significant reduction in number of medications or control of previously elevated blood pressure without a change in medications), or failed (all other responses). The study group included 28 patients (14 men, 14 women) with a mean age of 65 years. The preintervention and the first postintervention evaluations occurred within 180 days of the procedure. All patients were hypertensive, and all except one were under medical treatment. Mean duration of hypertension was 9.1 +/-8.8 years. There were 38 interventional procedures (28 unilateral, 10 bilateral) involving 41 renal arteries; seven arteries had two procedures done. Before angioplasty, all renal arteries had lesions of > or =60% diameter reduction by duplex scanning. Endovascular stents were deployed following angioplasty in 14 (34%) of the procedures. The technical result was classified as a success in 24 (63%), a partial success in 12 (32%) of the procedures, and two procedures (5%) were classed as technical failures. There were statistically significant reductions in blood pressure following successful and partially successful procedures, but cure of hypertension was achieved in only 11% of cases. There were no significant changes in creatinine in any of the technical result groups. Of the 38 renal arteries evaluated with duplex ultrasound following intervention, 39% were found to have stenosis of > or =0% involving a treated renal artery, including one postintervention occlusion. Cure of hypertension was rare in this patient population with atherosclerotic renal artery stenosis. More than one third of the treated renal arteries showed > or =0% lesions recurring after the procedure. Thirteen percent of those with technical success and 17% of those with partial technical success had creatinine improvement of at least 20% over the baseline value. Significant clinical and anatomic improvement were relatively uncommon following balloon angioplasty in this series of patients.


Subject(s)
Angioplasty, Balloon , Arteriosclerosis/diagnostic imaging , Arteriosclerosis/therapy , Renal Artery Obstruction/diagnostic imaging , Renal Artery Obstruction/therapy , Ultrasonography, Doppler, Duplex , Aged , Antihypertensive Agents/therapeutic use , Arteriosclerosis/complications , Blood Pressure/drug effects , Blood Pressure/physiology , Creatinine/blood , Female , Follow-Up Studies , Humans , Hypertension/complications , Hypertension/drug therapy , Male , Middle Aged , Renal Artery Obstruction/complications
10.
Circulation ; 104(17): 2051-6, 2001 Oct 23.
Article in English | MEDLINE | ID: mdl-11673345

ABSTRACT

BACKGROUND: High-resolution MRI has been shown to be capable of identifying plaque constituents, such as the necrotic core and intraplaque hemorrhage, in human carotid atherosclerosis. The purpose of this study was to evaluate differential contrast-weighted images, specifically a multispectral MR technique, to improve the accuracy of identifying the lipid-rich necrotic core and acute intraplaque hemorrhage in vivo. METHODS AND RESULTS: Eighteen patients scheduled for carotid endarterectomy underwent a preoperative carotid MRI examination in a 1.5-T GE Signa scanner using a protocol that generated 4 contrast weightings (T1, T2, proton density, and 3D time of flight). MR images of the vessel wall were examined for the presence of a lipid-rich necrotic core and/or intraplaque hemorrhage. Ninety cross sections were compared with matched histological sections of the excised specimen in a double-blinded fashion. Overall accuracy (95% CI) of multispectral MRI was 87% (80% to 94%), sensitivity was 85% (78% to 92%), and specificity was 92% (86% to 98%). There was good agreement between MRI and histological findings, with a value of kappa=0.69 (0.53 to 0.85). CONCLUSIONS: Multispectral MRI can identify the lipid-rich necrotic core in human carotid atherosclerosis in vivo with high sensitivity and specificity. This MRI technique provides a noninvasive tool to study the pathogenesis and natural history of carotid atherosclerosis. Furthermore, it will permit a direct assessment of the effect of pharmacological therapy, such as aggressive lipid lowering, on plaque lipid composition.


Subject(s)
Carotid Artery Diseases/diagnosis , Carotid Artery Diseases/metabolism , Hemorrhage/diagnosis , Lipid Metabolism , Magnetic Resonance Imaging , Carotid Arteries/metabolism , Carotid Arteries/pathology , Carotid Artery Diseases/complications , Carotid Artery Diseases/surgery , Endarterectomy, Carotid , Hemorrhage/complications , Humans , Magnetic Resonance Imaging/methods , Necrosis , Predictive Value of Tests , Sensitivity and Specificity
11.
J Appl Physiol (1985) ; 91(4): 1741-9, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11568158

ABSTRACT

We propose a model to measure both regional ventilation (V) and perfusion (Q) in which the regional radiodensity (RD) in the lung during xenon (Xe) washin is a function of regional V (increasing RD) and Q (decreasing RD). We studied five anesthetized, paralyzed, mechanically ventilated, supine sheep. Four 2.5-mm-thick computed tomography (CT) images were simultaneously acquired immediately cephalad to the diaphragm at end inspiration for each breath during 3 min of Xe breathing. Observed changes in RD during Xe washin were used to determine regional V and Q. For 16 mm(3), Q displayed more variance than V: the coefficient of variance of Q (CV(Q)) = 1.58 +/- 0.23, the CV of V (CV(V)) = 0.46 +/- 0.07, and the ratio of CV(Q) to CV(V) = 3.5 +/- 1.1. CV(Q) (1.21 +/- 0.37) and the ratio of CV(Q) to CV(V) (2.4 +/- 1.2) were smaller at 1,000-mm(3) scale, but CV(V) (0.53 +/- 0.09) was not. V/Q distributions also displayed scale dependence: log SD of V and log SD of Q were 0.79 +/- 0.05 and 0.85 +/- 0.10 for 16-mm(3) and 0.69 +/- 0.20 and 0.67 +/- 0.10 for 1,000-mm(3) regions of lung, respectively. V and Q measurements made with CT and Xe also demonstrate vertically oriented and isogravitational heterogeneity, which are described using other methodologies. Sequential images acquired by CT during Xe breathing can be used to determine both regional V and Q noninvasively with high spatial resolution.


Subject(s)
Lung/physiology , Pulmonary Circulation/physiology , Respiratory Mechanics/physiology , Xenon , Algorithms , Animals , Female , Hemodynamics/physiology , Image Processing, Computer-Assisted , Male , Models, Biological , Perfusion , Pulmonary Gas Exchange/physiology , Sheep , Tomography, X-Ray Computed
12.
Magn Reson Imaging ; 19(6): 795-802, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11551719

ABSTRACT

Measuring carotid artery plaque burden from MRI is a reliable method for monitoring regression and progression of atherosclerosis. However, to measure all available images would be very time consuming, and in practice the image quality (IQ) of these images may be inconsistent, which can directly impact the quality of measurement. It is hypothesized that if IQ is comparable among different contrast weighted images, then carotid artery area measurements obtained from different contrast images of the same location will produce identical results. To test this, T1, proton density and T2 weighted images were acquired from ten patients (51 +/- 7 years old). Carotid lumen and vessel wall area was measured using a custom designed software program. The results showed strong agreement evidenced with only small differences on both lumen (mean: 40.5 mm(2)) and wall (mean: 52.6 mm(2)) area measurement among different weighted images. The maximum absolute mean differences are less than 2.7 mm(2) and 4.4 mm(2), and 90(th) percentile of the absolute differences are 5.6 mm(2) and 8.2 mm(2) respectively. In conclusion, different contrast weighted images with high and comparable IQ will yield similar results in lumen and vessel wall area measurement. At each matched location, it is recommended that the image with the highest IQ be used for area measurement.


Subject(s)
Carotid Arteries/anatomy & histology , Magnetic Resonance Imaging/methods , Carotid Artery Diseases/diagnosis , Female , Humans , Intracranial Arteriosclerosis/diagnosis , Male , Middle Aged
13.
Cancer Res ; 61(16): 6025-8, 2001 Aug 15.
Article in English | MEDLINE | ID: mdl-11507046

ABSTRACT

We measured concentrations and ratios of mutagenic (8-OH) lesions to putatively nonmutagenic formamidopyrimidine (Fapy) lesions of adenine (Ade) and guanine (Gua) to elucidate radical (.OH)-induced changes in DNA of normal, normal from cancer, and cancer tissues of the prostate. The relationship between the lesions was expressed using the mathematical model log(10)[(8-OH-Ade + 8-OH-Gua)/(FapyAde + FapyGua)]. Logistic regression analysis of the log ratios for DNA of normal and cancer tissues discriminated between the two tissue groups with high sensitivity and specificity. Correlation analysis of log ratios for normal prostates revealed a highly significant increase in the proportion of mutagenic base lesions with age. Data from correlation analysis of the log ratios for normal tissues from cancer were consistent with an age-dependent, dose-response relationship. The slopes for both correlations intersected at approximately 61 years, an age when prostate cancer incidence is known to rise sharply. The age-related increase in the proportion of.OH-induced mutagenic base lesions is likely a significant factor in prostate cancer development.


Subject(s)
Adenine/analogs & derivatives , DNA Damage , Guanine/analogs & derivatives , Hydroxyl Radical/metabolism , Prostatic Neoplasms/genetics , Adenine/metabolism , Age Factors , Cell Transformation, Neoplastic/genetics , DNA/metabolism , DNA, Neoplasm/metabolism , Gas Chromatography-Mass Spectrometry , Guanine/metabolism , Humans , Hydroxyl Radical/toxicity , Logistic Models , Male , Middle Aged , Models, Biological , Prostate/metabolism , Prostate/physiology , Prostatic Neoplasms/metabolism , Pyrimidines/metabolism
14.
J Infect Dis ; 184(3): 268-77, 2001 Aug 01.
Article in English | MEDLINE | ID: mdl-11443551

ABSTRACT

In a prospective study, the etiology of community-acquired pneumonia (CAP) was investigated among consecutive patients admitted to an academic, urban public hospital in Seattle. The study population was uniquely young, was predominantly male, and had high rates of homelessness, cigarette smoking, alcoholism, injection drug use, and human immunodeficiency virus (HIV) infection. Leading causes of CAP among HIV-negative patients were aspiration, followed by Streptococcus pneumoniae, Legionella species, and Mycoplasma pneumoniae. Among HIV-positive patients, Pneumocystis carinii, Mycobacterium tuberculosis, S. pneumoniae, and M. pneumoniae were the most common etiologic agents. Severe CAP was associated with typical bacterial infections and aspiration pneumonia but not Legionella infection among HIV-negative patients and with Pseudomonas aeruginosa infections among HIV-positive patients. These findings emphasize the need to tailor empirical antibiotic therapy according to local patient populations and individual risk factors and highlight the importance of recognizing underlying HIV infection in patients who are hospitalized with CAP.


Subject(s)
Community-Acquired Infections/microbiology , HIV Infections/complications , Pneumonia, Bacterial/classification , Adult , Aged , Aged, 80 and over , Alcoholism , Blood Transfusion , Cocaine-Related Disorders , Community-Acquired Infections/epidemiology , Community-Acquired Infections/etiology , Comorbidity , Female , HIV Infections/epidemiology , HIV Infections/microbiology , HIV Seronegativity , Hospitals, Public/statistics & numerical data , Hospitals, Urban/statistics & numerical data , Humans , Legionellosis/diagnosis , Male , Marijuana Abuse , Middle Aged , Mycobacterium Infections/diagnosis , Pneumonia, Bacterial/epidemiology , Pneumonia, Bacterial/microbiology , Pneumonia, Mycoplasma/diagnosis , Pneumonia, Pneumococcal/diagnosis , Risk Factors , Smoking , Socioeconomic Factors , Substance Abuse, Intravenous , Tuberculosis, Pulmonary/diagnosis , Washington/epidemiology
15.
Magn Reson Med ; 44(6): 968-72, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11108636

ABSTRACT

High-resolution MRI may be used to monitor the progression of human carotid atherosclerosis by measuring the lumen and wall area changes over time. The purpose of this study was to analyze the precision of quantitative measurements of lumen and wall areas. Two independent MR scans near the carotid bifurcation were conducted on eight patients within 2 weeks. The error of lumen area measurement was 6. 2%, 9.2%, and 9.7% for T(1), proton density, and T(2)-weighted images, respectively, and the error of wall area measurement was 10. 8%, 10.9%, and 12.0%. The precision of area measurement correlates strongly with image quality.


Subject(s)
Carotid Arteries/pathology , Magnetic Resonance Angiography/methods , Algorithms , Carotid Artery Diseases/diagnosis , Diagnostic Errors/statistics & numerical data , Humans , Magnetic Resonance Angiography/instrumentation , Magnetic Resonance Angiography/standards , Magnetic Resonance Angiography/statistics & numerical data , Quality Control , Reproducibility of Results
16.
Proc Natl Acad Sci U S A ; 97(23): 12442-5, 2000 Nov 07.
Article in English | MEDLINE | ID: mdl-11058168

ABSTRACT

Structural changes in a 25-base DNA strand, induced by single 8-oxo-guanine or 8-oxo-adenine substitutions, were shown by using Fourier transform-infrared spectroscopy with multivariate statistics. Pronounced differences were demonstrated between the parent and derivatives with respect to base interactions and changes in the phospho-deoxyribose backbone. The greatest degree of change in the backbone likely occurred immediately adjacent to the 8-oxo group, potentially altering the stereochemistry at a distance. The 8-oxo lesions, formed from reactive oxygen species (e.g., hydroxyl radicals), may appreciably alter the conformational properties of strands at the replication fork, thus affecting the selectivity of polymerases, the proofreading capability of repair enzymes, and the fidelity of the transcriptional machinery.


Subject(s)
Adenine/analogs & derivatives , Adenine/chemistry , DNA Damage , DNA/chemistry , Guanine/analogs & derivatives , Guanine/chemistry , Nucleic Acid Conformation , Hydroxyl Radical , Multivariate Analysis , Oligodeoxyribonucleotides/chemistry , Spectroscopy, Fourier Transform Infrared/methods
17.
J Natl Cancer Inst Monogr ; (27): 147-56, 2000.
Article in English | MEDLINE | ID: mdl-10963626

ABSTRACT

The results obtained from experimental studies of estrogen carcinogenesis need validation in epidemiologic studies. Such studies present additional challenges, however, because variations in human populations are much greater than those in experimental systems and in animal models. Because epidemiologic studies are often used to evaluate modest differences in risk factors, it is essential to minimize sources of errors and to maximize sensitivity, reproducibility, and specificity. In the first part of this chapter, critical factors in designing and executing epidemiologic studies, as well as the influence of sample collection, processing, and storage on data reliability, are discussed. One of the most important requirements is attaining sufficient statistical power to assess small genetic effects and to evaluate interactions between genetic and environmental factors. The second part of this chapter describes innovative technology, namely, Fourier transform-infrared (FT-IR) spectra of DNA that reveal major structural differences at various stages of the progression from normal to cancer tissue. The structural differences become evident from wavenumber-by-wavenumber statistical comparisons of the mean FT-IR spectra of DNA from normal to cancer tissues. This analysis has allowed distinguishing benign tissues from cancer and metastatic tissues in human breast, prostate, and ovarian cancers. This analysis, which requires less than 1 microg of DNA, is predicted to be used for detecting early cancer-related changes at the level of DNA, rather than at the cellular level.


Subject(s)
Epidemiologic Research Design , Fourier Analysis , Precancerous Conditions/epidemiology , DNA, Neoplasm/analysis , Female , Gonadal Steroid Hormones/analysis , Humans , Male , Models, Statistical , Polymorphism, Genetic , Precancerous Conditions/genetics , Risk Factors
18.
Circulation ; 102(9): 959-64, 2000 Aug 29.
Article in English | MEDLINE | ID: mdl-10961958

ABSTRACT

BACKGROUND: The results of studies of advanced lesions of atherosclerosis suggest that the thickness of the fibrous cap that overlies the necrotic core distinguishes the stable lesion from one that is at high risk for rupture and thromboembolic events. We have developed a high-resolution MRI technique that can identify the fine structure of the lesion, including the fibrous cap, in vivo. The aim of the present study was to determine the agreement between in vivo MRI and lesion architecture as seen on histology and gross tissue examination to identify fibrous cap thickness and rupture. METHODS AND RESULTS: Twenty-two subjects who were scheduled for carotid endarterectomy underwent MRI with a 3-dimensional multiple overlapping thin slab angiography protocol. The appearance of the fibrous cap was categorized as (1) an intact, thick, (2) an intact, thin, or (3) a ruptured fibrous cap on MRI, gross, and histological sections. Thirty-six sites were available for comparison between MRI and histology. There was a high level of agreement between MRI and histological findings: 89% agreement, kappa (95% CI)=0.83 (0.67 to 1. 0), weighted kappa=0.87. Spearman's correlation coefficient was 0.88 (significant to the 0.01 level). CONCLUSIONS: These findings indicate that high-resolution MRI with a 3-dimensional multiple overlapping thin slab angiography protocol is capable of distinguishing intact, thick fibrous caps from intact thin and disrupted caps in atherosclerotic human carotid arteries in vivo. This noninvasive technique has the potential to permit studies that examine the relationship between fibrous cap changes and clinical outcome and to permit trials that evaluate therapy intended to "stabilize" the fibrous cap.


Subject(s)
Carotid Arteries/pathology , Carotid Stenosis/diagnosis , Endarterectomy, Carotid , Magnetic Resonance Imaging/methods , Carotid Artery, Common/pathology , Carotid Stenosis/pathology , Carotid Stenosis/surgery , Humans , Magnetic Resonance Angiography , Staining and Labeling
19.
J Appl Physiol (1985) ; 89(2): 445-57, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10926625

ABSTRACT

We assessed the influence of cranial-to-caudal inertial force (+G(z)) and the countermeasures of anti-G suit and positive pressure breathing during G (PBG), specifically during +G(z), on regional pulmonary blood flow distribution. Unanesthetized swine were exposed randomly to 0 G(z) (resting), +3 G(z), +6 G(z), and +9 G(z), with and without anti-G suit and PBG with the use of the Air Force Research Laboratory centrifuge at Brooks Air Force Base (the gravitational force of the Earth, that is, the dorsal-to-ventral inertial force, was present for all runs). Fluorescent microspheres were injected into the pulmonary vasculature as a marker of regional pulmonary blood flow. Lungs were excised, dried, and diced into approximately 2-cm(3) pieces, and the fluorescence of each piece was measured. As +G(z) was increased from 0 to +3 G(z), blood flow shifted from cranial and hilar regions toward caudal and peripheral regions of the lung. This redistribution shifted back toward cranial and hilar regions as anti-G suit inflation pressure increased at +6 and +9 G(z). Perfusion heterogeneity increased with +G(z) stress and decreased at the higher anti-G suit pressures. The distribution of pulmonary blood flow was not affected by PBG. ANOVA indicated anatomic structure as the major determinant of pulmonary blood flow.


Subject(s)
Gravitation , Gravity Suits , Pulmonary Circulation/physiology , Animals , Female , Fluorescent Dyes , Lung/metabolism , Lung/physiology , Microspheres , Positive-Pressure Respiration , Pulmonary Gas Exchange/physiology , Swine , Swine, Miniature
20.
Anesth Analg ; 90(3): 658-65, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10702453

ABSTRACT

UNLABELLED: The etiology of transient neurologic symptoms (TNS) after 5% lidocaine spinal anesthesia remains undetermined. Previous case reports have shown that patients acutely experiencing TNS have no abnormalities on neurologic examination or magnetic resonance imaging. The aim of our study was to determine whether volunteers with TNS would exhibit abnormalities in spinal nerve electrophysiology. Twelve volunteers with no history of back pain or neurologic disease underwent baseline electromyography (EMG), nerve conduction studies, and somatosensory-evoked potential (SSEP) testing. Then, the volunteers were administered 50 mg of 5% hyperbaric lidocaine spinal anesthesia and were placed in a low lithotomy position (legs on four pillows). The next day, all volunteers underwent follow-up EMG, nerve conduction, and SSEP testing and were questioned and examined for the presence of complications including TNS (defined as pain or dysthesia in one or both buttocks or legs occurring within 24 h of spinal anesthesia). Volunteers who had TNS underwent additional EMG testing 4-6 wk later. Five of the 12 volunteers reported TNS. No volunteer had an abnormal EMG, nerve conduction study, or SSEP at 24 h follow up, nor were there any changes in EMG studies at delayed testing in the five volunteers experiencing TNS. On statistical analysis, the right peroneal and the right tibial nerve differed significantly for all volunteers from pre- to postspinal testing. When comparing pre- and postspinal testing of the TNS and non-TNS volunteers, statistically significant changes occurred in the nerve conduction tests of the right peroneal and left tibial nerve. There was no difference in measurements of F response, H reflex latency, amplitude, or velocity for either leg. Multivariate analysis of variance showed no significant difference between TNS and non-TNS volunteers for the changes in the nine nerve conduction tests when considered together (P = 0.4). We conclude that acute TNS after lidocaine spinal anesthesia did not result in consistent abnormalities detectable by EMG, nerve conduction studies, or SSEP in five volunteers. IMPLICATIONS: Electrophysiologic testing in volunteers experiencing transient neurologic symptoms is not abnormal.


Subject(s)
Anesthesia, Spinal/adverse effects , Anesthetics, Local/adverse effects , Lidocaine/adverse effects , Peripheral Nervous System Diseases/chemically induced , Spinal Nerves/drug effects , Adult , Electromyography , Evoked Potentials, Somatosensory , Female , Humans , Male , Middle Aged , Neural Conduction/drug effects , Spinal Nerves/physiology , Subarachnoid Space
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