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Biomedical subjects

C W White

Publications and source records attributed to C W White.

At least 127 records · Page 7Linked to original sources

Changes in cross-sectional area of the coronary lumen in the six months after angioplasty: a quantitative analysis of the variable response to percutaneous transluminal angioplasty.

Although immediate and late changes in coronary stenoses after percutaneous transluminal coronary angioplasty (PTCA) have been reported, most investigators have employed qualitative or semiquantitative techniques to analyze the angiograms. Such data is not optimal because of considerable interobserver variability and the use of relative instead of absolute changes in lesion geometry. Analysis is further compounded by the indistinct edges that characterize coronary lesions immediately after angioplasty. To quantify the changes in minimal cross-sectional area (MCSA) of the coronary lumen that occur during and after PTCA, we analyzed the angiograms of 23 patients before PTCA, immediately after PTCA, and at 7.2 +/- 3.0 (mean +/- SD) months follow-up using two computer-assisted methods of angiographic analysis--quantitative coronary angiography (QCA) and videodensitometry (VID). QCA provides an absolute measure of the area of the lumen; VID is a nongeometric method that is not dependent on exact border recognition. Based on these quantitative methods, we found that successful angioplasty is associated with about a three-fold increase in the MCSA of the lesion (from 1.0 to 3.2 mm2). This area is, however, well below normal and is less than half of the average MCSA of the inflated dilating balloon. Analysis of follow-up angiograms demonstrated that eight of 23 patients had a substantial late increase in the MCSA of the lesion (from 2.7 to 4.1 mm2) after the angioplasty procedure. Clinical, hemodynamic, and angiographic characteristics immediately after PTCA were not predictive of MCSA of the lumen at follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

Application of Doppler technology to studies of the coronary circulation.

Presently available Doppler technology has allowed us to substantially increase our understanding of the regulation of the coronary circulation in humans. New technologic developments in this area promise to further enhance our understanding of the operational characteristics of the coronary circulation in patients in normal and pathologic states.

Angina Pectoris↗

Assessing the physiological significance of coronary obstruction in man.

At present, it is widely assumed that the physiological significance of a coronary obstruction can be assessed by measuring percent stenosis on a coronary arteriogram. This assumption is being challenged by physiological measurements of coronary reserve performed in patients at open heart surgery with a Doppler technique. These physiological studies have shown a poor correlation between coronary reserve and percent stenosis. Although stenoses at the ends of the spectrum (less than 10% or greater than 90% diameter narrowing) have expected effects on coronary reserve, stenoses of intermediate severity (10-90%) do not accurately predict coronary reserve in the individual vessel involved. Studies with quantitative angiography indicate that diffuse coronary atherosclerosis, undetected by angiography, is probably the dominant explanation for why percent stenosis does not accurately predict the physiologic significance of coronary obstructions in man. Because the 'gold standard' (percent stenosis) utilized for decades to assess the physiologic significance of coronary obstructive lesions has been seriously challenged, development of other more sophisticated approaches to this problem should be encouraged.

Animals↗

Occurrence of diploid strains of Cryptococcus neoformans.

A mating between niacin and pantothenate auxotrophs of Cryptococcus neoformans gave a few prototrophic progeny that were self-fertile. These were uninuclear but contained twice as much DNA as the parental strains. Segregation of nutritional markers was observed upon sporulation. We conclude that these self-fertile strains are diploids.

Cryptococcus↗

Dimethylthiourea consumption reflects H2O2 concentrations and severity of acute lung injury.

Even though dimethylthiourea (DMTU) effectively scavenges O2 metabolites in vitro, it is often unclear if scavenging of O2 metabolites is the mechanism by which DMTU decreases tissue injury in biological models. Since DMTU not only scavenges O2 metabolites but is also consumed in a dose-response manner following reaction with hydrogen peroxide (H2O2) in vitro, we wondered whether DMTU would also be consumed by O2 metabolites in biological systems and if DMTU consumption would then reflect O2 metabolite concentrations and O2 metabolite-mediated injury. Our results supported this possibility. We found that selected nonprotecting concentrations of DMTU were consumed in isolated rat lungs perfused with H2O2 and that the amounts of DMTU consumed reflected both the added amounts of H2O2 and the corresponding degrees of H2O2-induced acute edematous injury. DMTU consumption was relatively specific for reaction with H2O2 occurring in isolated lungs that were injured by H2O2 but not lungs injured by elastase, oleic acid, histamine, or a venous pressure challenge. Our results suggest that measurement of DMTU consumption may be useful for assessing the presence and toxicity of O2 metabolites and the specificity of the protective effects of DMTU in biological systems.

Animals↗

Transluminal, subselective measurement of coronary artery blood flow velocity and vasodilator reserve in man.

Assessment of coronary blood flow and the vasodilator reserve capacity of individual coronary arteries in the catheterization laboratory has been hampered by methodologic limitations. We have developed and validated a small Doppler catheter that can subselectively measure phasic coronary blood flow velocity (CBFV). In seven anesthetized calves, CBFV was varied from 0.1 to 5.7 times control CBFV. Changes in mean CBFV measured intraluminally by catheter in the left anterior descending and left circumflex arteries were similar to those measured simultaneously with an epicardial Doppler probe on the surface of the same vessel (n = 85, r = .95, slope = 1.04) and to changes in coronary sinus flow (n = 69, r = .97, slope = 1.06) measured with timed venous collections. Identical maximal coronary reactive hyperemic responses with the catheter present and absent in the artery being studied demonstrated that coronary obstruction by the catheter was minimal. Safety studies in six additional calves demonstrated that the catheter caused small changes in coronary endothelial permeability. Histologic studies revealed no endothelial denudation or thrombus formation. Stable phasic recordings of coronary blood flow velocity have been obtained in 58 of 70 patients studied. One of the 70 patients studied had abrupt coronary occlusion probably related to catheter-induced vasospasm. In 10 normal patients, intracoronary meglumine diatrizoate increased CBFV to 3.5 times that at rest (range 2.8 to 5.0). CBFV rose 5.0-fold after an intravenous infusion of dipyridamole (range 3.8 to 7.0). In each patient, dipyridamole produced greater vasodilation than meglumine diatrizoate. The time- and dose-response characteristics to dipyridamole infusion were heterogeneous, underscoring the advantage of continuous on-line measurement of CBFV in the measurement of vasodilator reserve. This method of measuring CBFV and assessing vasodilator reserve in the catheterization laboratory should facilitate studies of the coronary circulation in man.

Animals↗

Effect of superoxide dismutase encapsulated in liposomes or conjugated with polyethylene glycol on neutrophil bactericidal activity in vitro and bacterial clearance in vivo.

Encapsulation in liposomes (LIP) or conjugation with polyethylene glycol (PEG) are methods being used to increase circulating half-life periods and/or improve delivery of antioxidant enzymes that could decrease lung injury induced by O2 metabolites. We found that pretreatment with LIP, with or without the antioxidant enzyme, superoxide dismutase (SOD), decreased killing of Staphylococcus aureus 502A by neutrophils in vitro and clearance of intravenously injected S. aureus in rabbits in vivo. In contrast, pretreatment with PEG (with or without SOD) had no effect on neutrophil bactericidal activity in vitro or bacterial clearance in vivo. Our results suggest that conjugation with PEG may be a better way than encapsulation in liposomes for delivering antioxidant enzymes, especially if one is concerned about preserving host-defense mechanisms.

Animals↗

Pulmonary antioxidant defense mechanisms.

Intrinsic enzymatic and non-enzymatic pulmonary antioxidant defense mechanisms undoubtedly protect the lung against oxidant-mediated environmental stresses and diseases. In addition, new ways of augmenting pulmonary antioxidant defenses are being developed which can be used to bolster disease-overwhelmed intrinsic lung defense mechanisms. Improved understanding of antioxidant defense mechanisms will increase our knowledge of the causes and suggest rational approaches for treating oxidant-induced lung injury.

Acetylcysteine↗

The effectiveness of continuing medical education in changing the behavior of physicians caring for patients with acute myocardial infarction. A controlled randomized trial.

A randomized controlled trial was done to assess the ability of continuing medical education to change physicians' knowledge and behavior in the care of patients with acute myocardial infarction. Patient care practices on eight objectives were audited 6 months before and after physicians completed a 2-hour educational program. Sixty-three physicians from eight randomly selected communities constituted the experimental group and 40 physicians from four similar communities served as controls. The average score for desired care practices over all objectives increased from 48.5% to 60% (p less than 0.001). Three objectives showed significantly greater gains for physicians in the experimental group. The generalizability of these effects was also studied in two additional educational contexts: a multitopic and a unitopic university-based continuing medical education program. Similar significant changes in behavior resulted in both contexts. Significant overall increases in knowledge occurred and persisted for all groups. Continuing medical education can effect changes in physicians' knowledge and care practices that can persist for at least 6 months.

Cardiology↗

Influence of baseline ejection fraction and success of thrombolysis on mortality and ventricular function after acute myocardial infarction.

The efficacy of streptokinase (STK) thrombolytic therapy was prospectively evaluated in 77 consecutive patients presenting within 9 hours of onset of acute myocardial infarction. Serial left ventricular (LV) ejection fraction (EF) was assessed by radionuclide ventriculography, initially (acute) and at 1 month (late). The role of initial LVEF was examined by comparing patients with an acute LVEF greater than or equal to 50% (type I) with those with LVEF less than 50% (type II). Sixty-five patients (84%) had total coronary occlusion and received STK. Initial successful reperfusion was achieved in 34 patients (52%), but repeat angiograms at 10 to 14 days revealed persistent patency in only 27 patients. Within the type I and type II classification, 2 patient subgroups were compared: Group A had successful and persistent thrombolysis and group B had initial failure of thrombolysis or in-hospital reocclusion. There was no significant change in global LVEF in any group from acute to 1 month follow-up: group IA--acute EF = 56 +/- 2% (mean +/- standard error of the mean), late EF = 55 +/- 2% (p = not significant [NS]); group IB--acute EF = 58 +/- 1%, late EF = 55 +/- 2% (NS); group IIA--acute EF = 35 +/- 2%, late EF = 4 +/- 4%, (NS); group II B--acute EF = 36 +/- 2%, late EF = 41 +/- 3% (NS). No patient with an acute EF greater than or equal to 50% died, i.e., group IA patients (n = 7) or group IB patients (n = 13).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Systemic markers of fibrinolysis after unsuccessful intracoronary streptokinase thrombolysis for acute myocardial infarction. Does nonreperfusion indicate failure to achieve a systemic lytic state?

Reasons for the failure of intracoronary streptokinase (STK) to result in coronary thrombolysis were examined in 45 patients with acute myocardial infarction presenting with angiographic evidence of total coronary occlusion. In 25 patients (group A), clot lysis was initially successful; in 20 (group B), reperfusion was unsuccessful. The STK dosage in group A ranged from 84,000 to 310,000 units (mean 188,000 +/- 12,000); STK dosage in group B ranged from 160,000 to 360,000 units (mean 267,000 +/- 11,000 [p less than 0.05]). Before therapy, levels of fibrin degradation products and serum fibrinogen were normal in all patients. After intracoronary STK, fibrin degradation products and serum fibrinogen levels changed similarly in both groups. Eight-five percent of patients in group B had evidence of a systemic fibrinolytic state. These data suggest that higher doses of STK administered in the same manner are unlikely to result in an increased reperfusion rate. Systemic hematologic markers of fibrinolysis are not helpful in explaining the success or failure of intracoronary thrombolysis.

Coronary Angiography↗

Does visual interpretation of the coronary arteriogram predict the physiologic importance of a coronary stenosis?

To assess visual interpretation of the coronary arteriogram as a means of predicting the physiologic effects of coronary obstructions in human beings, we compared caliper measurements of the degree of coronary stenosis with the reactive hyperemic response of coronary flow velocity studied with a Doppler technique at operation, after 20 seconds of coronary arterial occlusion. In 39 patients (44 vessels) with isolated, discrete coronary lesions varying in severity from 10 to 95 per cent stenosis, measurement of the percentage of stenosis from coronary angiograms was not significantly correlated (r = -0.25) with the reactive hyperemic response. Results were the same for obstructions in the left anterior descending, diagonal, and right coronary arteries. Underestimation of lesion severity occurred in 95 per cent of vessels with greater than 60 per cent stenosis of the diameter by arteriography. Both overestimation and underestimation of lesions with less than 60 per cent stenosis were common. These results, together with the high interobserver and intraobserver variability of standard visual analysis of angiograms, suggest that the physiologic effects of the majority of coronary obstructions cannot be determined accurately by conventional angiographic approaches. The need for improved analytical methods for the physiologic assessment of angiographically detected coronary obstructions is apparent.

Angiography↗

Angiographic evidence that reciprocal ST-segment depression during acute myocardial infarction does not indicate remote ischemia: analysis of 23 patients.

Although reciprocal ST-segment depression from the remote noninfarcting ventricular wall during acute myocardial infarction (MI) is a common clinical finding, the significance of this electrocardiographic pattern is unclear. Previous retrospective studies have suggested that these findings may reflect either remote wall ischemia, multivessel coronary artery disease (CAD), extensive MI or a benign electrical phenomenon. Prior studies have lacked angiographic data obtained at the time of these acute electrocardiographic changes. In this study we prospectively evaluated 23 patients with acute MI. Left ventricular wall motion, coronary anatomy and the ECG were all assessed over a short period during the acute phase of the MI. Segmental wall motion was used as a sensitive indicator of ischemia. Seventeen patients had acute anterior MI, of whom 47% had reciprocal ST-segment depression; 6 patients had inferior MI, with 3 showing reciprocal ST depression. The mean degree of ST-segment elevation from the infarcting wall tended to be greater in patients with reciprocal ST-segment depression than in those without such reciprocal ST depression (2.8 +/- 0.4 vs 1.9 +/- 0.3 mm, p = 0.06). Patients with and without reciprocal ST-segment depression had similar degrees of segmental dysfunction in the infarct wall. However, no abnormalities in segmental wall motion in the remote wall were seen regardless of the presence or absence of remote wall ST-segment depression. In addition, the presence or absence of ST-segment depression did not predict the extent or degree of CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Monitoring demyelination in multiple sclerosis with multi-flash campimetry.

Multi-flash campimetry is a computer-implemented psychophysical technique that allows a rapid and extensive assessment of visual flicker sensitivity. Multi-flash field maps generated from the data typically reveal the presence of 'islands' of degraded temporal resolution in multiple sclerosis (MS) patients, but not in normal control observers. These distinct 'islands' presumably reflect the influence of demyelination as well as a variety of other possible transient factors, such as edema and inflammation of the optic nerve. The question addressed in the present study concerned a means of distinguishing among such influences. The strategy employed was to test MS patients more than once over a period of several months. Under the assumption that there is little or no significant remyelination in the central nervous system, it was argued that 'islands' that remain present over time should be those that principally reflect demyelination. Transient changes that appear in the fields of MS patients probably reflect the influence of other mediating factors. Examples of multi-flash field maps are presented to illustrate this point and to serve as an initial assessment of the reliability of the technique. It is concluded that multi-flash campimetry may prove to be an effective aid in documenting the degree of progressive visual involvement in MS, and provide a means of monitoring the clinical course of demyelination in the visual system.

Adult↗

Combined intracoronary streptokinase and percutaneous coronary angioplasty for reperfusion of chronic total coronary occlusion.

In a 40 year old man with a 1 month total occlusion of a dominant right coronary artery, persistent angina despite medical management indicated inadequate coronary collateral supply to the posterolateral myocardium originally supplied by the totally occluded vessel. Initial attempts at reperfusion of the chronically occluded vessel with an angioplasty guide wire and balloon were unsuccessful. However, administration of intracoronary streptokinase resulted in partial reperfusion, after which successful wire-guided balloon angioplasty was accomplished. This case illustrates the potential utility of combining a thrombolytic agent with angioplasty in attempting reperfusion for management of selected cases of chronic total coronary artery occlusion.

Adult↗

Rethrombosis after reperfusion with streptokinase: importance of geometry of residual lesions.

We tested the hypothesis that lesion rethrombosis after streptokinase reperfusion is related to luminal size of the residual stenosis. Two independent techniques of analyzing coronary angiograms, quantitative coronary angiography and computer-based videodensitometry, were used to estimate the size of the residual lumen immediately after discontinuation of streptokinase. These techniques were selected because they provide independent estimates of cross-sectional area of a lesion with high degrees of reproducibility and minimal observer variability. Twenty-four patients who had undergone successful reperfusion with streptokinase were studied. Seven patients had lesion rethrombosis documented either on a repeat angiogram, at autopsy, or, in one case, by the fact that the patient had an acute transmural infarction resulting in death. Vessel patency was documented by repeat coronary angiography 8 to 14 days after initial streptokinase reperfusion in the other 17 patients. As assessed by quantitative coronary angiography, seven of 13 patients (54%) with minimal luminal cross-sectional areas of less than 0.4 mm2 had rethrombosis. None of the 11 patients with lumens greater than 0.4 mm2 had rethrombosis. In the 17 patients with vessels that remained patent the size of the residual lesion at repeat catheterization was compared with its size immediately after reperfusion with streptokinase. Over the intervening 8 to 14 day interval, an average percentage increase in minimal cross-sectional area of 116 +/- 34% was observed. In seven patients minimal luminal cross-sectional area more than doubled. Integrated optical density, an index of the severity of coronary stenosis derived from computer-based videodensitometry, was also useful in identifying a subgroup of patients at high risk for rethrombosis of lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Computers↗