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Biomedical subjects

C R Ayers

Publications and source records attributed to C R Ayers.

At least 19 recordsLinked to original sources
PubMed2001

Safety of CO(2)- and gadodiamide-enhanced angiography for the evaluation and percutaneous treatment of renal artery stenosis in patients with chronic renal insufficiency.

OBJECTIVE: The objective of our study was to evaluate the safety of CO(2) and gadodiamide angiography for diagnosing and percutaneously treating renal artery stenosis in patients with chronic renal insufficiency and presumed ischemic nephropathy. SUBJECTS AND METHODS: One hundred forty-six consecutive patients with chronic renal insufficiency (serum creatinine > 1.5 mg/dL) were examined for renal artery stenosis using CO(2) and gadodiamide as the angiographic contrast agents. If renal artery stenosis was detected, percutaneous balloon angioplasty with or without stenting was performed. In patients for whom 48-hr creatinine levels were available, we performed an analysis to determine the incidence of contrast-involved nephropathy (increase in serum creatinine of 0.5 mg/dL at 48 hr without identifiable cause). Major complications were reported up to 1 week, and mortality was reported up to 30 days after the procedure. RESULTS: Ninety-five patients had serum creatinine levels available at 48 hr. An increase in creatinine of greater than 0.5 mg/dL at 48 hr occurred in three patients (3.2%), presumably caused by CO(2), by gadodiamide, or by both. Neither diabetes nor the degree of preexisting chronic renal insufficiency was a predictor of worsening renal function 48 hr after the procedure. The volumes of CO(2) and gadodiamide used for diagnostic studies alone versus the volume used for interventional studies was not significantly different (for CO(2), p = 0.09; for gadodiamide, p = 0.30). Eleven major complications occurred in eight patients (5.5%). Two deaths (1.4%) occurred within 30 days. One death was due to cholesterol embolization and the other was not believed to be related to the procedure. CONCLUSION: Angiography and percutaneous treatment of renal artery stenosis in patients with chronic renal insufficiency and suspected ischemic nephropathy can be performed relatively safely using CO(2) and gadodiamide as angiographic contrast agents without an increased risk of complications. Contrast-induced nephropathy potentially occurred in 3.2% of patients. Neither the degree of underlying renal insufficiency nor diabetes was a risk factor for predicting a greater likelihood of renal function worsening at 48 hr of follow-up. The volumes of CO(2) and gadodiamide used in this study did not result in an increased risk of contrast-involved nephropathy.

Adult↗
PubMed1995

Elevated serum lipoprotein(a) is a risk factor for clinical recurrence after coronary balloon angioplasty.

BACKGROUND: Elevated lipoprotein (Lp) (a) concentrations are associated with coronary artery disease and myocardial infarction. Lp(a) is structurally related to proteins involved in lipid transport, fibrinolysis, coagulation, and cellular mitogenesis and is known to have important physiological interactions with the coagulation and fibrinolytic systems. Because these processes may be important to arterial healing after balloon injury, we hypothesized that elevated Lp(a) concentrations may be associated with recurrence of symptoms and restenosis after balloon angioplasty. METHODS AND RESULTS: We assessed 240 consecutive patients undergoing coronary balloon angioplasty with measurements of Lp(a), total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoprotein A-I, and apolipoprotein B-100 concentrations from fresh specimens. Patients were evaluated 4 to 6 months after angioplasty for clinical recurrence by repeat angiography if angina had returned or by maximal exercise treadmill testing with thallium imaging if patients remained asymptomatic. Ninety-seven patients (40%) had clinical recurrence; 143 (60%) did not. Patients with recurrence had significantly greater Lp(a) concentrations compared with those without (median, 29 versus 14; P < .0001). Each patient quintile stratified by increasing Lp(a) concentrations had incrementally greater recurrence rates ranging from 27% (lowest quintile) to 60% (highest quintile). By multivariate logistic regression analysis, Lp(a) concentration was the only predictor of recurrence (P < .0001). A subset of frozen, stored serum samples showed a significant decrease in measured Lp(a) concentration over time (mean, 605 days; P < .01). CONCLUSIONS: An elevated Lp(a) concentration was a risk factor for clinical recurrence after percutaneous transluminal balloon coronary angioplasty. Other lipid levels or clinical characteristics were not significantly associated with recurrence. When serum was frozen and stored for a prolonged period, Lp(a) concentration decreased over time.

Angioplasty, Balloon, Coronary↗
PubMed1995

Assessment of the reliability of the determination of carotid artery lumen sizes by quantitative image processing of magnetic resonance angiograms and images.

In order to use MR imaging to assess progression or regression of atherosclerosis, one must have an idea of the reproducibility of the imaging and image processing techniques. The ability of dark-blood MRI and semiautomated image processing to reproducibility measure the inner boundary of the carotid arteries was evaluated and compared with results obtained using bright-blood MRA. MRI and MRA images were obtained for two normal and two diseased volunteers six times each over a short period of time (6 months). The carotid bifurcation was used to align slices from different imaging sessions. The area for each vessel (right and left common, internal and external carotid artery) was determined for the six imaging sessions. The standard deviations of each lumen area normalized to the average area were computed for each vessel segment for each volunteer. For the common, internal, and external carotids, the averaged normalized standard deviations for MRI were 8, 12, and 17% and for MRA were 6, 8, and 13%. Lumen sizes obtained by MRI and MRA were found to be not statistically different. Eccentric plaques not seen on MRA were visualized by MRI. In conclusion, dark-blood MRI with semiautomated image processing yields reliable lumen areas that are in agreement with those obtained by MRA.

Adult↗
PubMed1995

New diagnostic inroads in hypertension and atherosclerosis.

In the past two to three decades, the practice among hypertension specialists has been to lower blood pressure with the strong assumption that morbidity and mortality would be reduced. This was largely based on large clinical trials done in the 1960s and 1970s that did not include angiotensin-converting enzyme inhibitors or calcium-channel blockers. Performing large clinical trials is expensive and the results often do not apply to individual patients. Until recently, noninvasive methods to monitor end-organ effects of elevated blood pressure and other cardiovascular risk factors were limited. The development of high-resolution ultrasound and evolving magnetic resonance technology will allow early detection of heart and blood vessel changes and will make monitoring of the progression and regression of disease possible. This will allow better selection of treatment programs for each patient.

Arteriosclerosis↗
PubMed1994

Hemodynamic and metabolic correlates of dipyridamole-induced myocardial thallium-201 perfusion abnormalities in multivessel coronary artery disease.

The mechanisms responsible for the development of reversible thallium-201 (TI-201) defects with dipyridamole stress in patients with coronary artery disease (CAD) is not well understood. Previous experimental animal studies have demonstrated coronary steal characterized by an absolute decrease in subendocardial flow distal to a stenosis in response to dipyridamole infusion. Accordingly, the purpose of this study was to determine if reversible TI-201 defects in response to dipyridamole infusion are reflective of myocardial ischemia or secondary to regional differences in flow reserve. Dipyridamole (0.56 mg/kg) TI-201 imaging was performed in 23 patients in whom serial electrocardiographic, hemodynamic, aortic and coronary sinus lactate, and coronary sinus adenosine measurements were obtained. All patients with CAD had TI-201 redistribution (3.8 +/- 2.0 defects/patient), and all patients without CAD had normal scans. Mean aortic pressure was similar in both groups and did not change in response to dipyridamole (non-CAD 103 +/- 11 vs CAD 99 +/- 15 mm Hg, p = NS). Pulmonary capillary wedge pressure was similar at baseline (non-CAD 11 +/- 4 vs CAD 13 +/- 5 mm Hg, p = NS) and did not change in response to the drug (non-CAD 14 +/- 3 vs CAD 15 +/- 7 mm Hg, p = NS). Lactate extraction fraction was similar at baseline (non-CAD 0.22 +/- 0.09 vs CAD 0.17 +/- 0.14, p = NS) and decreased similarly in both groups (non-CAD 0.08 +/- 0.06 vs CAD 0.05 +/- 0.12, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1993

Noninvasive quantitative evaluation of atherosclerosis using MRI and image analysis.

A new medical image analysis system to quantify atherosclerosis in the lower abdominal aorta using magnetic resonance imaging is described. This medical image analysis and display system permits the quantification of the three-dimensional (3D) properties of the vessel wall and lumen cross-sectional area and volumes. Preliminary results of employing this medical image analysis capability on magnetic resonance images demonstrated a twofold increase in wall volume per unit vessel length, corresponding to intimal thickening, before luminal narrowing was detected. This work demonstrated the feasibility and usefulness of quantitatively evaluating the 3D properties of the vessel lumen and wall by using a combination of magnetic resonance imaging and image analysis. The demonstration that intimal wall thickening is observed in images before observable occlusion of the lumen can be expected to provide an important early indicator of the future development of atherosclerosis. Such capability will permit detailed and quantitative studies to assess the effectiveness of therapies, such as drug, exercise, and dietary regimens.

Aorta↗
PubMed1992

The precise radioimmunoassay of adenosine: minimization of sample collection artifacts and immunocrossreactivity.

Anti-adenosine antibodies were produced in rabbits immunized with N6-carboxymethyladenosine conjugated to methyl albumin. 125I-N6-Aminobenzyladenosine was synthesized and used as a high-specific-activity, high-affinity ligand. A radioimmunoassay (RIA) was developed that can detect 6.25 nM (312.5 fmol) of underivatized adenosine and cross-reacts less than 0.02% with adenine nucleotides and guanosine and not at all with 1 mM inosine. The sensitivity of the RIA can be increased to a detection limit of 0.125 nM (6.25 fmol) by derivitizing samples with benzyl bromide to form N6-benzyladenosine. The assay was adapted to an automated RIA procedure. Assay precision was increased by: (i) inhibiting slight adenosine deaminase activity present in anti-sera; (ii) treating buffers and albumin used in the RIA with charcoal to remove contaminating adenosine; and (iii) correcting for a small but variable component of immunoreactivity not attributable to adenosine. A second antibody prepared with a 2',3'-disuccinyladenosine-albumin conjugate was also found to detect some non-adenosine-mediated immunoreactivity in plasma samples. Immunointerference in human plasma was eliminated in samples treated with ZnSO4/Ba(OH)2 or partially purified over C18 Sep Paks to remove nucleotides and assayed after sample benzylation or succinylation. Human blood was mixed with a novel "stop" solution that was optimized to inhibit adenosine formation from AMP by greater than 99% and to inhibit adenosine uptake into red cells and degradation by greater than 94%. Human plasma/stop solution was assayed by RIA and HPLC with equivalent results.

Adenine↗
PubMed1992

Improved detection of ischemia-induced increases in coronary sinus adenosine in patients with coronary artery disease.

Attempts to monitor coronary sinus adenosine as a clinical marker of myocardial ischemia in humans have been disappointing. Accordingly, procedures have been developed for detecting adenosine in blood collected from the human coronary sinus. Collection involves using a double-lumen metabolic catheter, which allows blood to be mixed with a stop solution at the catheter tip, thereby minimizing adenosine formation and degradation. A five-component stop solution almost completely arrests adenosine formation and degradation. Adenosine analysis is improved by using both boronate and C18 Sep-Pak columns to purify and concentrate adenosine in human plasma before HPLC. Plasma adenosine in the coronary sinus of patients with and without coronary artery disease, measured before and during peak atrial pacing, showed a twofold atrial pacing-induced increase in adenosine in the patients with coronary artery disease (n = 9, P less than 0.001) but no change in the patients with normal epicardial coronary arteries (n = 6). These preliminary results indicate that coronary sinus adenosine may provide an index of myocardial ischemia in patients with coronary artery disease.

Adenosine↗
PubMed1991

Radiographic contrast agents and platelet function: a quenched-flow study.

Radiographic contrast media (RCM) may alter platelet behavior at concentrations achieved during cardiac angiography. We used quenched-flow aggregometry coupled to single-particle counting to study the influence of RCM on the kinetics of platelet aggregation (less than 5.0 sec) induced by adenosine diphosphate (ADP, 2.86 microM). At a concentration in platelet-rich plasma (PRP) of 5 per cent RCM by volume, platelet aggregation was inhibited by diatrizoate, iopamidol and ioxaglate either directly or following incubation of each contrast agent with PRP for 20 minutes. Diatrizoate inhibited more than did iopamidol or ioxaglate (56 +/- 6, versus 39 +/- 3 and 40 +/- 9 per cent respectively; P less than 0.003, p less than 0.009, n = 20 normal subjects). A small reduction (about 16 per cent) in aggregation velocity occurred within 5 seconds of exposure of PRP to all 3 RCM and the onset time (t) or lag period before aggregation begins was significantly prolonged by diatrizoate (p less than 0.03). The RCM vehicles alone (iodinated moiety removed, osmolality readjusted) had no effect on the ADP-induced aggregation. Platelet counts fell significantly after incubation with diatrizoate (12%; p = 0.04). Our data therefore show that early platelet aggregation was inhibited by 3 commonly-used ionic and nonionic contrast agents. Inhibition was apparently caused by the iodinated contrast molecule, began within seconds of platelet-RCM contact and was independent of vehicle composition. Since diatrizoate inhibited aggregation more than iopamidol or ioxaglate, its use may be of additional value during angiographic procedures in clinical situations involving enhanced platelet activation.

Adult↗
PubMed1989

Atrial natriuretic factor in essential hypertension.

We measured circulating levels of immunoreactive atrial natriuretic factor (ANF) in 10 patients with untreated, uncomplicated mild to moderate essential hypertension and in 15 normotensive controls. ANF concentrations were significantly higher in the hypertensive group than in the control group (38.4 +/- 6.9 pg/ml versus 18.3 +/- 1.8 pg/ml, p less than 0.02). A positive correlation between ANF levels and systolic, diastolic and mean blood pressure was noted in the total study population (p less than 0.008, r = 0.52; p less than 0.005, r = 0.55; p less than 0.02, r = 0.46, respectively). Thus, plasma ANF concentrations are elevated in essential hypertension and may result from increased intraarterial pressure.

Adult↗
PubMed1989

Platelet calcium and quenched-flow aggregation kinetics in essential hypertension.

Abnormal platelet function may contribute to the complications of essential hypertension. We have studied the kinetics of platelet aggregation induced by adenosine diphosphate (ADP) or epinephrine, plasma beta-thromboglobulin, and basal, cytosolic, and free calcium, as correlates of platelet function. Fifteen untreated patients with essential hypertension and without detectable atherosclerosis, 18-40 years old, were compared with 30 matched normotensive control subjects. Maximal rates of platelet aggregation (Vmax) with ADP and epinephrine were significantly higher in patients than in control subjects (p less than 0.03), as assessed by quenched-flow aggregometry. However, significance was lost when Vmax was corrected for the platelet count. Paradoxically, the activation constants (Ka) for ADP were higher in patients than in control subjects (p less than 0.03). With ADP as the inducing agent, onset time (t) or lag period before aggregation begins was longer in patients than in control subjects (p less than 0.02). beta-thromboglobulin levels, an index of in vivo platelet activation, were not significantly different between the two groups (p = 0.13). The mean platelet cytosolic free calcium concentration was higher in patients (213 +/- 19 nM) than in control subjects (172 +/- 14 nM), but this difference was not statistically significant (p = 0.07). However, there was a close correlation between the free calcium level and systolic, diastolic, and mean blood pressure (p less than 0.003, p less than 0.04, p less than 0.004, respectively). No difference in platelet volume between the two groups was found. Our data suggest that platelets in the early stages of essential hypertension display an overall increased aggregation potential but a diminished sensitivity to ADP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1989

Plasma renin activity and albumin excretion in teenage type I diabetic subjects. A prospective study.

Plasma renin activity (PRA) may be high among teenage and young adult insulin-dependent diabetic subjects. Supine PRA and stimulated PRA were therefore measured in 50 female and 50 male diabetic subjects, 13-20 years old, diagnosed before the age of 16. Fifty percent have been restudied after 4.6 +/- 0.2 (mean +/- SEM) years. Initially, 43% had high PRA (supine 4.0 +/- 0.37, stimulated 12.02 +/- 0.8 ng/ml/hr angiotensin I), 45% had normal activity (supine 2.89 +/- 0.26, stimulated 6.47 +/- 0.34 ng/ml/hr/angiotensin I), and 12% had low activity (supine 1.57 +/- 0.05, stimulated 3.09 +/- 0.08 ng/ml/hr/angiotensin I). Levels were directly associated with prepubertal duration of diabetes and were inversely associated with duration of diabetes after onset of puberty but not with total duration or patient age. Within 4.6 +/- 0.2 years the percentage of subjects with high PRA fell to 13%, and the percentage of those with low PRA rose to 35%. Initially 51% of the cohort had normal albumin excretion rates (AER) at rest and during exercise equal to or less than 10 micrograms/min/m2; 32% had elevated rates only during exercise of 39 +/- 5 micrograms/min/m2; 13% had elevated rates at rest of 41 +/- 8 micrograms/min/m2 and during exercise of 116 +/- 21 micrograms/min/m2; and 4% had clinical proteinuria at rest and during each exercise period equal to or greater than 150 micrograms/min/m2. After 5 years, 58% continued to have normal AER, or their AER improved.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

High-resolution 1H NMR spectral signature from human atheroma.

Coronary artery disease due to atherosclerosis takes the lives of approximately 550,000 Americans each year--an enormous toll. Put in economic terms, the cost to the United States alone has been estimated to exceed 60 billion dollars annually. We have found that well-resolved proton (1H) NMR spectra can be obtained from human atheroma (fatty plaque), despite its macroscopic solid appearance. The fraction of the total spectral intensity corresponding to the sharp 1H NMR signals is temperature dependent and approaches unity at body temperature (37 degrees C). Studies of the total lipids extracted from atheroma and cholesteryl esters were conducted to identify the chemical and physical origin of the spectral signature. The samples were characterized through assignment of their chemical shifts and by measurement of their T1 and T2 relaxation times as a function of magnetic field strength. The results suggest that the relatively sharp 1H NMR signals from human atheroma (excluding water) are due to a mixture of cholesteryl esters, whose liquid-crystalline to isotropic fluid phase transition is near body temperature. Preliminary applications to NMR imaging of human atheroma are reported, which demonstrate early fatty plaque formation within the wall of the aorta. These findings offer a basis for noninvasive imaging by NMR to monitor early and potentially reversible stages of human atherogenesis.

Aorta↗
PubMed1988

Identification and 3-D quantification of atherosclerosis using magnetic resonance imaging.

Cardiovascular disease due to atherosclerosis is a leading cause of death in the United States as well as other developed countries. This paper describes the development of image processing, pattern recognition, and graphical display techniques to non-invasively quantify the atherosclerotic disease process using magnetic resonance imaging (MRI). We have demonstrated the ability to identify the soft tissue classes of (1) normal, smooth muscle wall, (2) fatty plaque, (3) complex, fibrous plaque, and (4) calcified plaque. The objective of this work has been to combine functional information, such as plaque tissue type, with structural information, represented by 3-D display of vessel structure, into a single composite display. The results of this work provide a "high information content" display which will aid in the diagnosis and analysis of the atherosclerotic disease process, and permit detailed and quantitative studies to assess the effectiveness of therapies (e.g. changes in diet, exercise and drug administration).

Aorta↗
PubMed1987

High-resolution proton NMR spectra of human arterial plaque.

Well-resolved proton (1H) NMR spectra of solid human arterial plaque can be acquired. Studies have been carried out of human fatty plaque obtained postmortem (ex vivo), the total lipids extracted from human atheroma, and a model mixture of cholesteryl esters whose lipid composition resembles that of human atheroma. In each case, well-resolved 1H NMR spectra were obtained at body temperature (37 degrees C), with little or no underlying broad signal. Such sharp 1H NMR spectra are typical of isotropic fluids, whereas solid and liquid-crystalline materials give rise to much broader spectral lines. The results suggest the sharp 1H NMR spectra of human atheromatous lesions at body temperature are due largely to the presence of intracellular and extracellular droplets of cholesteryl esters in the isotropic liquid phase. These findings provide a necessary basis for use of 1H NMR techniques to image quantitatively the lipid constituents of human atheroma in vivo, and to study their chemical and physical properties.

Adult↗