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Biomedical subjects

T J Ryan

Publications and source records attributed to T J Ryan.

At least 343 records · Page 19Linked to original sources

Follow-up of patients from the coronary artery surgery study (CASS) potentially suitable for percutaneous transluminal coronary angioplasty.

To determine the proper place for percutaneous transluminal coronary angioplasty (PTCA) among the therapeutic options available for patients with coronary heart disease, one must compare the results of PTCA with those obtained by conventional medical and surgical therapy. To develop a cohort comparison group, we interrogated the Coronary Artery Surgery Study (CASS) registry, and patients with proximal discrete subtotal stenosis (70% to 99%) involving the right, left anterior descending, circumflex, or left main coronary artery, singly or with stenoses in two of the three major coronary arteries, were selected; 796 patients (3.7% of all patients enrolled in CASS from 1975 to 1979) met these selection criteria. Surgical therapy was chosen in 53.3%; surgical mortality was low and there was excellent 4-year actuarial survival. There was significant improvement in functional class. Survival was also excellent in medically treated patients. Medically treated patients also had significant improvement in functional class in comparison with baseline values. The data presented here characterize a cohort group against which the clinical results of PTCA can be evaluated and compared.

Angina, Unstable↗

Efficacy and safety of incremental doses of diltiazem for the treatment of stable angina pectoris.

The safety and efficacy of incremental doses of diltiazem in treating angina pectoris were assessed in 20 patients with functional class II to III exertional angina. During an initial single-blind dose titration phase, dilitiazem produced a dose-related improvement in anginal frequency and exercise capacity. Weekly anginal attacks were reduced to 7.5 +/- 8.9, 5.6 +/- 7.8 and 4.9 +/- 7.3 on diltiazem, 120, 240 and 360 mg per day, respectively, as compared with 11.9 +/- 8.7 on placebo (all p less than 0.001). Treadmill time was significantly enhanced by high dose (360 mg per day) as compared with moderate dose (240 mg per day) diltiazem: 473 +/- 149 versus 424 +/- 146 seconds (p less than 0.05). Time to ischemic ST segment depression was similarly changed: 344 +/- 132 versus 298 +/- 142 seconds (p less than 0.05) by high dose as compared with moderate dose diltiazem. During a subsequent double-blind phase, high dose diltiazem significantly reduced weekly anginal frequency when compared with placebo: 3.1 +/- 3.0 versus 9.3 +/- 7.1 (p less than 0.001); and increased treadmill exercise time: 508 +/- 158 versus 418 +/- 172 seconds on placebo (p less than 0.05). Subjective and objective benefits of high dose diltiazem were sustained during a follow-up period of 6 months without major drug side effects.

Adult↗

Experience with latrogenic pediatric vascular injuries. Incidence, etiology, management, and results.

During a 32-month period, 79 extremities in 76 children (age 1 day-13 years, mean = 31 months) were evaluated with regard to iatrogenic vascular injuries. Prospectively, 42 children were studied pre- and post-cardiac catheterization. Ten of these children sustained vascular injuries (incidence = 24%). Thirty-four additional children were referred because of 35 iatrogenic vascular injuries as a result of transfemoral cardiac catheterization (n = 20), umbilical artery catheterization (n = 10), or recent surgery (n = 5). All 45 injuries were evaluated by lower extremity segmental Doppler pressure measurements in addition to routine physical examination at the time of injury and at frequent follow-up. An ankle/brachial pressure index (ABI) less than 0.9 was considered abnormal. Selected children (ABI less than 0.9 for greater than 30 days) underwent orthoroentgenograms to assess limb growth. The average ABI immediately following injury was 0.34 +/- 0.33. Thirty-four injuries were treated nonoperatively. Twelve injuries were excluded from further study due to death (n = 7) or being lost to follow-yp (n = 5). A return of ABI to normal was seen from 1 day to 2 years in 93% of children treated with heparin (n = 14) compared to 63% of children who were simply observed (n = 8) (p less than 0.10). The initial severity of ischemia did not correlate with the subsequent rate of improvement. Only patients with absent femoral pulses were selected for operative intervention, which consisted of aortic thrombectomy (n = 2), femorofemoral bypass (n = 2), femoral artery patch angioplasty (n = 1), or femoral artery thrombectomy (n = 7) with no mortality. Nine patients had immediate return of a normal ABI after surgery. A delayed return of ABI to normal occurred in the other two. Nine per cent of surgically treated children and 23% of nonsurgically treated children developed leg length discrepancies (0.5-3.0 cm) as a result of ischemia lasting greater than 30 days. Overall, 91% of the children in this series eventually regained normal circulation following injury and no child lost a limb. This study indicates that iatrogenic pediatric vascular injuries are common and can result in significant limb growth impairment. Immediate operative intervention is highly successful when the injury is proximal to the common femoral artery bifurcation and avoids the prolonged ischemia seen with nonoperative therapy. For more distal occlusions, heparin therapy provides better results than simple observation. Although therapeutic intervention for these injuries is generally successful, a limb length discrepancy rate of 14% mandates that indications for invasive vascular monitoring and diagnostic procedures be strict.

Adolescent↗

Biochemical modulation of angiogenesis in the chorioallantoic membrane of the chick embryo.

A variety of substances potentially having effects on angiogenesis in the skin were assayed on the chorioallantoic membrane of the chicken embryo (CAM). Millipore filter discs alone and saturated with saline 0.9% (controls), keratinocyte-conditioned medium, lactic acid 10(-1) M, adenosine 10(-4) M, sodium fluoride 10(-4) M, dinitrophenol 10(-4) M, histamine 10(-4) M, 5-hydroxytryptamine 10(-4) M, acetylcholine 10(-4) M, prostaglandin E2 3 X 10(-4) M, prostaglandin F2 alpha 3 X 10(-4) M, arachidonic acid 10(-4) M, epidermal growth factor 5 X 10(-5) g/ml, human plasma fibronectin 10(-4) g/ml, acetylsalicylic acid 10(-3) M, and arachis oil were applied to the CAM and the vascular responses quantitated 4 days later. None of the agents with the exception of keratinocyte-conditioned medium stimulated new vessel growth as compared to the controls. However, arachis oil (p less than 0.001) and ADP (p less than 0.01) were associated with significantly decreased vascular responses relative to controls. The specimens incubated with saline, fibronectin, ADP, and arachis oil were examined histologically; with the exception of arachis oil all displayed ectodermal epithelial and mesenchymal hyperplasia of the membrane in association with increased vascularity. Almost no perceptible change was noted histologically with arachis oil.

Acetylcholine↗

The importance of elastic fibres in skin lymphatics.

Elastic fibres lie in intimate contact with dermal lymphatics. Demonstration of elastic by an orcein stain enables lymphatics to be identified and differentiated from blood capillaries. The finding of elastic suggests it plays an important role in the normal functioning of lymphatics.

Animals↗

Coronary arteriography and coronary artery bypass surgery: morbidity and mortality in patients ages 65 years or older. A report from the Coronary Artery Surgery Study.

Of 2144 patients age 65 years or older entered into the registry of the Coronary Artery Surgery Study (CASS) who had coronary arteriography, 1086 underwent isolated coronary artery bypass grafting. Complications of angiography included death in four patients and nonfatal myocardial infarction in 17. Eight patients suffered neurologic complications, which were transient in five. The perioperative mortality was 5.2% (57 of 1086), which is significantly greater than the perioperative mortality of 1.9% (151 of 7827) in patients younger than 65 years entered in CASS (p less than 0.001). There was a trend toward an increased mortality rate with age; it was 4.6% (37 of 803) in patients age 65-69 years, 6.6% (16 of 241) in those 70-74 years and 9.5% (four of 42) in those 75 years or older. The duration of hospital stay after operation was significantly longer for the patients 65 years or older than for the patients younger than 65 (13.3 vs 11.4 days; p less than 0.001). Stepwise linear discriminant analysis identified five variables predictive of perioperative mortality: presence of 70% or more stenosis of the left main coronary artery and a left-dominant circulation, left ventricular end-diastolic pressure, a history of current cigarette smoking, pulmonary rales on auscultation, and presence of one or more associated medical diseases. A second linear discriminant analysis, incorporating 7658 CASS patients who underwent isolated coronary artery bypass surgery irrespective of age, examined whether age 65 years or older was an independent predictor of perioperative mortality. The variables selected, in order of significance, were congestive cardiac failure score, left main coronary artery stenosis and a left-dominant circulation, age 65 years or older, left ventricular wall motion score, sex and history of unstable angina pectoris. In patients 65 years or older, the mortality from coronary arteriography is low, whereas mortality from coronary artery bypass surgery is greater than that in CASS patients younger than 65 years.

Aged↗

Left main coronary artery stenosis: angiographic determination.

Reliability of angiographic assessment of the left main coronary artery segment was evaluated by review of 106 coronary cineangiograms from the Coronary Artery Surgery Study. The films were interpreted by three groups of angiographers: those at a clinical site, those at a quality control site, and those on a study census panel. Among the readings of these three groups, there was 41% to 59% agreement on the severity of the lesion, with 80% agreement on whether the lesion was greater or less than 50%. The severity of lesion, its location, or presence of ectasia or calcium did not affect the discrepancy rate, whereas segments that were unusually short, diffusely diseased, or obscured by overlapping vessels were especially difficult to interpret.

Arterial Occlusive Diseases↗

The mechanism of transluminal angioplasty: evidence for formation of aneurysms in experimental atherosclerosis.

Quantitative histologic examination (morphometric analysis) of pressure-perfused rabbit atherosclerotic arteries was used to determine whether compression of atheromatous material occurs with transluminal angioplasty. Experimental atherosclerosis was developed in both iliac arteries, with transluminal angioplasty performed on the left iliac while the right iliac served as a nondilated control. Angiography showed equal degrees of luminal narrowing before angioplasty (p = NS). Angioplasty reduced the left iliac narrowing in all animals studied. Morphometric analysis of histologic sections of the left and right iliac arteries disclosed significant differences in luminal and total vessel areas (p less than .05), whereas arterial wall (intima and media) areas were similar (p = NS). Dilated areas often demonstrated marked intimal splitting with dissection into the media. At higher magnification, loss of nuclear staining and dense layers of extracellular matrix consistent with stretching were frequently seen. It is concluded that the major mechanism of successful transluminal angioplasty is stretching of the vessel, resulting in localized aneurysm formation. Intimal splitting implies inelasticity of the neointima. No evidence of compression and remodeling of atheromatous material was disclosed in this study.

Aneurysm↗

Prognostic value of angiographic indices of coronary artery disease from the Coronary Artery Surgery Study (CASS).

The Coronary Artery Surgery Study, CASS, enrolled 24,959 patients between August 1975 and June 1979 who were studied angiographically for suspected coronary artery disease. This paper compares the prognostic value for survival without early elective surgery of eight different indices of the extent of coronary artery disease: the number of diseased vessels, two indices using the number of proximal arterial segments diseased, two empirically generated indices from the CASS data, and the published indices of Friesinger, Gensini, and the National Heart and Chest Hospital, London. All had considerable prognostic information. Typically 80% of the prognostic information in one index was also contained in another. Our analysis shows that good prediction from angiographic data results from a combination of left ventricular function and arteriographic extent of disease. Prognosis may reasonably be obtained from three simple indices: the number of vessels diseased, the number of proximal arterial segments diseased, and a left ventricular wall motion score. These three indices account for an estimated 84% of the prognostic information available. 6-yr survival varies between 93 and 16% depending upon the values of these three indices.

Angiography↗

Serial angiographic evidence of rapid resolution of coronary artery stenosis.

An example of rapid, spontaneous resolution of an eccentric coronary luminal narrowing from 95 percent to 80 percent and subsequently to 50 percent stenosis over a six-week time period is presented. Spontaneous thrombolysis is proposed as the explanation for these changes and is discussed with reference to existing experimental and clinical observations.

Angina Pectoris↗

Interobserver variability in interpreting contrast left ventriculograms (CASS).

Randomly selected left ventricular cineangiograms performed by 14 medical centers (clinical sites) participating in a large multicenter study of medical and surgical treatment of coronary artery disease (CASS) were systematically recalled and reread by one of four designated quality control centers. The end diastolic volume (EDV), end systolic volume (ESV), and ejection fraction (EF) calculated by the quality control center were compared with those calculated by the clinical site, and correlation coefficients of 0.71, 0.84, and 0.79, respectively, were obtained. Regional left ventricular (LV) wall motion abnormalities were assessed by dividing the LV wall as viewed in the right anterior oblique (RAO) and left anterior oblique (LAO) views into five segments each and grading the motion of each segment according to six categories of increasing abnormalities from normal to aneurysm. When discrepancies based on "nearest neighbor" differences in naming adjacent segments were eliminated and only marked differences of more than one degree of severity of wall motion abnormality were considered, interobserver differences were 7% and 10% for RAO and LAO segments, respectively. Agreement was less frequent in designating a segment "aneurysmal." When each LV segment was assigned a numerical score based on increasing severity of wall motion abnormality and a total LV score for each ventriculogram computed, the quality control and clinical site readings were in good agreement with a correlation coefficient of 0.83.

Cardiac Volume↗

Determinants of clinical response and survival in patients with congestive heart failure treated with captopril.

The efficacy of chronic ambulatory captopril (CPT) therapy was evaluated over an 18-month period in 36 patients with refractory chronic congestive heart failure (CHF) by cardiac catheterization, treadmill exercise, nuclear scintigraphy, echocardiography, and symptomatology. Clinical improvement to New York Heart Association functional class I or class II was observed in 63% of the patients (20 of 32) after 2 months of treatment; this amelioration of CHF symptoms was sustained in 63% of the patients (10 of 16) at 18 months. Exercise tolerance increased in 64% of the patients (16 of 25) at early follow-up and in 79% (11 of 14) at late follow-up. Univariate analysis revealed that the pre- and post-CPT stroke work indices (SWI) and the post-CPT cardiac index related to favorable long-term clinical response. Fourteen CHF patients (39%) died during the 18-month follow-up. Univariate analysis revealed that the pretreatment SWI, right atrial pressure, plasma norepinephrine concentration, and echocardiographic shortening fraction were significant predictors of mortality. Multivariate analysis indicated that the SWI was the principal determinant of survival: the 18-month cumulative survival rate for CHF patients with a SWI less than 32 gm . m/m2 was 44% compared to 88% when the SWI was greater than 32 gm . m/m2. Thus, CPT results in sustained symptomatic and functional improvements in patients with advanced CHF, but the mortality remains high and is primarily related to the severity of cardiac dysfunction.

Acute Kidney Injury↗

Prognostic significance of angiographically documented left ventricular aneurysm from the Coronary Artery Surgery Study (CASS).

In order to evaluate the prognosis of medically treated patients with angiographically defined left ventricular aneurysm the data available from 1,136 patients with aneurysm (7.6 percent) from 15,019 patients with coronary artery disease in the Coronary Artery Surgery Study (CASS) registry were analyzed. Prior myocardial infarction, reduced ejection fraction, absence of angina and evidence of congestive heart failure were more commonly present in patients with aneurysm. The cumulative survival rates of medically treated patients at 1, 2, 3 and 4 years were 90, 84, 79 and 71 percent, respectively. The Cox analysis of survival indicated that the following variables predicted outcome: age, residual left ventricular function as assessed with angiography, left ventricular end-diastolic pressure, functional impairment due to congestive heart failure, number of vessels diseased, mitral regurgitation and S3 gallop. When survival was stratified for similar degrees of left ventricular dysfunction and functional impairment there was no difference between the survival of patients with aneurysm and that of registry patients without aneurysm. The data from this large population study indicate that the survival of patients with left ventricular aneurysm is better than previously recognized. The mortality in this group is primarily related to age, left ventricular function and clinical severity of heart failure. The presence of an aneurysm does not independently alter survival.

Coronary Angiography↗

Decrease in systolic blood pressure during exercise testing: reproducibility, response to coronary bypass surgery and prognostic significance.

To investigate the reproducibility and prognostic significance of an exercise-induced decrease in systolic blood pressure, 47 patients were identified who manifested such a reduction below the pre-exercise standing level in a consecutive series of 436 patients who underwent treadmill exercise testing and cardiac catheterization during a 3 year period. The prevalence of this abnormal finding was 11 percent in the total group but 21 percent in the 124 patients with three vessel or left main coronary artery disease. Patients with an exercise-induced reduction in systolic blood pressure were more likely to be male, have typical angina pectoris with class III or IV functional limitation and to have had a prior myocardial infarction than were patients without this finding (p less than 0.05). Although no complications occurred during the exercise test of these 47 patients, the majority had severe ischemic responses and 14 (30 percent) showed complex repetitive ventricular arrhythmias. Of the 47 patients, 24 (group 1a) received medical treatment and 23 (group 1b) underwent coronary bypass surgery. On repeat exercise testing in 42 patients, a decrease in systolic blood pressure during exercise was consistently present in group 1a (17 of 20) but entirely absent (0 of 22) in group 1b (p less than 0.001). The mean treadmill time, peak heart rate and systolic blood pressure were not significantly different in the initial and on repeat exercise tests in patients in group 1a; however, in patients in group 1b, all of these variables were significantly higher in the repeat test (p less than 0.001). At a mean follow-up time of 37 months, the total cardiac mortality rate was 8 percent (2 of 24) in group 1a and 4 percent (1 of 23) in group 1b. It is concluded that a decrease in systolic blood pressure during exercise testing is highly reproducible and appears to be reversed by coronary bypass surgery.

Angina Pectoris↗

Coronary hemodynamic effects of angiotensin inhibition by captopril and teprotide in patients with congestive heart failure.

The coronary hemodynamic effects of vasodilator therapy with angiotensin-converting enzyme inhibitors (captopril and teprotide) were studied in 11 patients with ischemic heart disease and severe congestive heart failure (CHF). Over 2 hours, systemic vascular resistance was reduced from 2,408 +/- 240 to 1,715 +/- 170 dynes . s . cm-5 (p less than 0.001), and cardiac output improved 18%, resulting in lower arterial pressure (101 +/- 8 to 86 +/- 5 mm Hg, p less than 0.001) and left ventricular filling pressure (30 +/- 2 to 21 +/- 2 mm Hg, p less than 0.001). Coronary sinus thermodilution blood flow paralleled perfusion pressure but did not significantly vary overall (160 +/- 20 to 133 +/- 12 ml/min, difference not significant [NS]). Coronary vascular resistance was unchanged. Although the left ventricular stroke work index rose slightly (37.7 +/- 8.8 to 41.3 +/- 7.9 g l m/m2, p less than 0.05), there was no change in the coronary arteriovenous oxygen content difference (10.8 +/- 1.0 to 10.4 +/- 1.0 ml/10 ml, NS) or calculated myocardial oxygen consumption (16.4 +/- 1.9 to 13.9 /- 1.6 ml/min, NS). The heart rate-systolic blood pressure product declined significantly during this period (8,824 +/- 703 to 7,087 +/- 514 beats . mm Hg, p less than 0.02); this relief of cardiac effort was a function of the pretreatment plasma renin activity. A derived index of external myocardial efficiency improved 37% (19 +/- 3 to 26 +/- 6, p less than 0.05), reflecting greater left ventricular work without increased oxygen demand. Enhancement of myocardial performance after converting enzyme inhibition appears dependent on reduction of angiotensin-mediated ventricular afterload and preload. The lack of coronary vasomotor effects in patients with advanced ischemic cardiomyopathy may reflect limited coronary vascular reserve. Improvement of heart failure in these patients developed without evidence of myocardial ischemia, since balance was maintained between oxygen supply and demand.

Aged↗