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Biomedical subjects

T J Ryan

Publications and source records attributed to T J Ryan.

At least 307 records · Page 17Linked to original sources
PubMed1984

Estradiol preferentially enhances extracellular tissue plasminogen activators of MCF-7 breast cancer cells.

MCF-7 human breast cancer cells secrete two immunologic types of plasminogen activator, one related to urokinase, the other unrelated. We have now examined whether estrogen stimulation of secreted plasminogen activator activity reflects an increase in one or both types. Examined semiquantitatively by sodium dodecyl sulfate-polyacrylamide gel electrophoretic zymography, the conditioned media of control cells were seen to contain a major activator band (Mr approximately 54,000) immunologically related to urokinase and a barely discernible doublet (Mr approximately 64,000 and Mr approximately 68,000). Addition of estradiol or, at much higher concentrations, testosterone led to marked enhancement of doublet activity, while the 54-kDa band was invariant. The 64-68-kDa doublet was immunoreactive with antiserum directed against Bowes melanoma tissue plasminogen activator but not with antiurokinase antibodies. Enhancement of doublet activity was correlated with hormone-induced increases in total secreted plasminogen activator activity. Neither progesterone nor dexamethasone increased total activity or the 64-68-kDa zones of lysis. Estradiol and testosterone alterations were blocked by appropriate concentrations of an estrogen antagonist (LY156758), actinomycin D, or cycloheximide. Regulation of MCF-7 cell-secreted tissue plasminogen activators thus appears to be mediated by an estrogen receptor process and to require sustained RNA and protein synthesis.

Breast Neoplasms↗
PubMed1984

Esterase A is a proteinase from rat urine that can activate plasminogen.

A proteinase which can activate human, dog and rat plasminogen to plasmin has been isolated from the urine of female rats, using affinity chromatography on benzamidine-coupled Sepharose. Inhibition by diisopropylfluorophosphate, tosyl-L-lysine chloromethylketone and benzamidine classified the enzyme as trypsin-like. The proteinase has weak activity on alpha-casein and hemoglobin, but will not lyse fibrin clots. It readily cleaves arginyl amides, including synthetic substrates specific for human glandular kallikrein and other serine proteinases. A chromogenic substrate for human urokinase (pyro Glu-Gly-Arg-pNA) is a poor substrate for the rat proteinase. Characteristics of the enzyme, such as its molecular weight (25 900), kinetic parameters and inhibition by aprotinin, indicate that this proteinase is esterase A, described by several investigators. Esterase A is shown not to be a true urinary plasminogen activator but rather is a unique arginine-specific proteinase. Urokinase-like and kallikrein-like activity are part of a broader proteolytic activity displayed by this enzyme.

Animals↗
PubMed1984

Effect of antiplatelet therapy on restenosis after experimental angioplasty.

Restenosis is recognized as a common complication of PTCA and can limit the long-term benefit of this procedure. To study the effect of antiplatelet agents in preventing restenosis, 25 New Zealand rabbits had bilateral iliac stenoses created by balloon deendothelialization and a 2% cholesterol diet for 6 weeks. After angiographic delineation of the iliac atherosclerosis, successful angioplasty was performed in all rabbits, with an average increase in luminal diameter of 0.9 mm (81%). Seven rabbits received aspirin (32 mg/day) plus dipyridamole (25 mg/day) and 9 received sulfinpyrazone (100 mg/day); 9 were given no antiplatelet drugs and served as controls. After 4 weeks of drug therapy and a continued atherogenic diet, angiography was repeated and the rabbits were killed for histologic examination. The angiographic luminal diameter was similar for these groups both before and immediately after angioplasty. However, the luminal diameter 4 weeks later was significantly larger in both the aspirin plus dipyridamole and the sulfinpyrazone groups compared with the control rabbits (1.3 +/- 0.6 and 1.8 +/- 0.5 mm vs 0.7 +/- 0.6 mm, respectively, p less than 0.05). Histologic examination revealed intraluminal clot in 4 of 9 control rabbits and in none of the drug-treated rabbits. Also, less intimal thickening was evident. In conclusion, aspirin plus dipyridamole and sulfinpyrazone inhibited angiographic restenosis after transluminal angioplasty in this experimental model. These findings support the use of antiplatelet agents in clinical angioplasty and suggest that platelet aggregation at the angioplasty site may promote restenosis.

Angioplasty, Balloon↗
PubMed1984

Role of percutaneous transluminal coronary angioplasty in the treatment of unstable angina. Report from the National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty and Coronary Artery Surgery Study Registries.

The acute and long-term consequences of PTCA performed in patients with unstable angina was determined in 442 patients with 1-vessel CAD who were enrolled in the NHLBI PTCA Registry. These patients were compared with 214 similar patients in the PTCA Registry with stable angina and with 330 patients with unstable angina from the NHLBI CASS Registry who underwent CABG. The 3 groups had similar baseline characteristics. The immediate angiographic success after PTCA was not different between patients with stable and those with unstable angina. The in-hospital mortality rate was 0.9% for the PTCA group with unstable angina and 0.47% for the PTCA group with stable angina. The combined 18-month mortality and MI rate was low in both groups (10.8 and 9.5%, respectively). No differences were observed in the mortality and MI rates between patients with unstable angina treated surgically or with PTCA. Both revascularization procedures markedly reduced symptoms of angina. Ninety-two percent of the PTCA group reported improvement in their angina, whereas 80% of the surgical group had a reduction in angina (p less than 0.05). The results from this observational study suggest that PTCA can be performed as safely and successfully in patients with unstable angina as in those with stable angina. PTCA compares favorably with CABG in patients with unstable angina in that the procedure is associated with low mortality and morbidity rates, while marked improvement in symptoms can be expected. Thus, PTCA could be considered an alternative to CABG in patients with unstable angina who have the appropriate anatomic characteristics.

Angina Pectoris↗
PubMed1984

Design of comparative clinical studies of percutaneous transluminal coronary angioplasty using estimates from the Coronary Artery Surgery Study.

The design of a prospective randomized trial of PTCA is discussed. It is suggested that patients with proximal subtotal occlusion of 1 or more vessels may be candidates for such a trial. Medical therapy as a control of 1-vessel CAD, medical or surgical therapy as a control for 2-vessel CAD (with 1 dilatable vessel) cases and surgical therapy as a control for 3-vessel CAD are most congruent with current practice. Possible criteria for comparison of PTCA with a control therapy include vital status, angina with daily activities, angina upon maximal exercise testing, MI, hospitalization, work status, cost, follow-up angiographic assessment, follow-up radionuclide ventriculography, measurement of immediate anatomic or hemodynamic change during initial treatment and quality-of-life indexes. These 10 measures are evaluated with respect to 9 desirable attributes for outcome criteria: the importance of the quantity measured, reproducibility, accuracy, low influence of investigator bias, low influence of subject bias, the measure is inexpensive and easy to obtain, sufficient occurrence to detect important differences, convenient to patients and measuring impairment due to disease. Examination of data from the Coronary Artery Surgery Study suggests that (1) a trial based on mortality alone is not feasible (because of a needed sample size in the thousands); (2) a trial using a combined death and/or MI end point would need approximately 1,000 cases even for patients with multivessel CAD; (3) approximately 950 patients would be needed in a trial to evaluate return to work (within 10%); (4) a trial based on pain relief (within 15% of the control group) would need 500 subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1984

Ventricular arrhythmias during exercise testing: mechanism, response to coronary bypass surgery and prognostic significance.

To investigate the determinants and prognostic significance of ventricular arrhythmias during exercise testing, 86 patients with such arrhythmias were identified from a consecutive series of 446 patients who underwent treadmill exercise testing and cardiac catheterization. The prevalence of these arrhythmias was 19% in the total group but increased to 30% in the 120 patients with 3-vessel or left main coronary artery disease. Patients with exercise-induced arrhythmias were more likely to have 3-vessel or left main coronary artery disease, a lower resting ejection fraction, greater than or equal to 2 mm of ischemic ST depression and more severe segmental wall motion abnormalities than patients without this finding (p less than 0.05). Repeat exercise testing in 22 patients with exercise-induced arrhythmias after coronary bypass surgery revealed that persistence of these arrhythmias was associated with either severe wall motion abnormalities preoperatively or residual ischemic ST depression during the post-operative exercise testing. At a mean follow-up period of 5.3 years, the presence of exercise-induced ventricular arrhythmias was not associated with increased cardiac mortality in the medically treated patients.

Arrhythmias, Cardiac↗
PubMed1984

Redistribution of regional blood flow following angiotensin-converting enzyme inhibition. Comparison of normal subjects and patients with heart failure.

The systemic and regional circulatory effects of angiotensin-converting enzyme inhibition were investigated in 30 normal subjects and in 36 patients with severe congestive heart failure. Regional blood flow was measured in individual patient groups. Cardiac index rose and systemic vascular resistance fell in normal subjects after angiotensin-converting enzyme inhibition. In the patients with heart failure, a similar rise in cardiac index and fall in systemic resistance occurred. In addition, right and left ventricular filling pressures decreased. The fall in systemic vascular resistance correlated with plasma renin activity (r = 0.57, p less than or equal to 0.001). Of the regional circulations investigated in normal subjects, only forearm blood flow increased after angiotensin-converting enzyme inhibition. Although over-all there was no change in renal or coronary blood flow, coronary flow dramatically increased in some patients and the increase in flow correlated with plasma renin activity (r = 0.939, p less than or equal to 0.001). In patients with heart failure, forearm, splanchnic, and coronary flow were unaffected by angiotensin-converting enzyme inhibition, whereas renal blood flow estimated from para-aminohippurate clearance increased 60 percent and accounted for 50 percent of the increase in cardiac output seen in these patients. Thus, redistribution of flow occurs in congestive heart failure with a significant reduction in the fraction flow to the kidneys when compared with normal flow. The contribution of the renin-angiotensin system to the regulation of regional blood flow is different in normal subjects and in patients with heart failure. Angiotensin-converting enzyme inhibition augments skeletal flow in normal subjects whereas it increases renal blood flow in patients with heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Electrocardiogram of the athlete: an analysis of 289 professional football players.

The electrocardiogram (ECG) of athletes reflects physiologic cardiovascular adaptations that occur in well-conditioned individuals. To more clearly define electrocardiographic changes seen in predominantly power-trained athletes, the ECGs of 289 apparently healthy professional football players were analyzed in detail. The players, aged 21 to 35 years, one-third of whom were black, had a mean body surface area of 2.24 m2, a mean heart rate at rest of 56 +/- 9 beats/min (with 77% (223) having a rate of less than 60 beats/min), and a mean P axis of 30 +/- 25 degrees. A wide QRS-T angle (greater than 60 degrees) was present in 14% (41 players) of the group. The mean PR interval was 0.18 +/- 0.02 second (greater than 0.21 in 9% [26 players]). Although two-thirds of the players had a QRS duration of 0.10 second, only 1 had right bundle branch block and none had left bundle branch block. The sum of S in lead V1 plus R in lead V5 averaged 37 +/- 9 mm, with 35% (101 players) demonstrating voltage criteria for left ventricular hypertrophy. The S + R value varied inversely with weight (r = -0.27, p less than 0.002). The maximum T height in any lead had a mean of 8.6 +/- 3 mm, with 22% (64 players) having a T height greater than or equal to 11 mm. U waves were universally present. ST-T changes mimicking ischemia were noted in 39 of 289 players (13%), 22 (58%) of whom were black (p less than 0.001). The maximal J-point elevation in any lead averaged 1.9 +/- 0.9 mm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Crossover femorofemoropopliteal sequential bypass for combined ipsilateral iliac and femoropopliteal occlusive disease.

We evaluated the effectiveness of crossover femorofemoropopliteal sequential bypass in 13 patients with combined ipsilateral iliac and femoropopliteal disease. Of them, eight underwent bypass grafting for limb salvage, and five, for disabling claudication. Four of the patients with claudication had relief of symptoms and significant increases in treadmill walking time. The cumulative limb salvage rate in the patients operated on for limb salvage was 88%. At 42 months, the cumulative patency rate for the femorofemoral portion of the graft was 91%, and for the distal segment, 63%. Mean ankle-brachial indices increased from 0.37 +/- 0.12 preoperatively to 0.76 +/- 0.16 postoperatively in the recipient limb. Early experience suggests that crossover sequential femorofemoropopliteal bypass grafts are effective in achieving limb salvage and relief of claudication, especially in patients with relative contraindications to major intra-abdominal surgery.

Aged↗
PubMed1984

The efficacy and safety of high-dose verapamil and diltiazem in the long-term treatment of stable exertional angina.

The efficacy and safety of high-dose verapamil (480 mg/day) and diltiazem therapy (360 mg/day) were compared in separate cohorts of 26 and 20 patients, respectively. All patients had stable exertional angina and underwent an initial 6-week double-blind, placebo-controlled, randomized phase followed by a 12-month open-label period. Angina attacks were reduced by verapamil (6.3 +/- 7.5 to 2.5 +/- 4.1 attacks per week, p less than 0.001) and by diltiazem (9.2 +/- 7.5 to 3.0 +/- 3.1 attacks per week, p less than 0.001), while treadmill time increased with both verapamil (372 +/- 132 to 444 +/- 108 s, p less than 0.001) and diltiazem (412 +/- 175 to 536 +/- 164 s, p less than 0.001) during the short-term study. Both agents continued to show similar salutory effects at the end of one year. The beneficial effects of both drugs appeared to be related in part to a reduction of the rate-pressure product during submaximal exercise (12% by verapamil, 7% by diltiazem, both p less than 0.05). Adverse effects were few and consisted primarily of mild constipation in six patients taking verapamil, and pedal edema and transient flushing in 2 patients each using diltiazem. Thus, high-dose verapamil and diltiazem have similar beneficial effects and are safe for the long-term treatment of effort-related angina pectoris.

Angina Pectoris↗
PubMed1984

Prognostic importance of a clinical profile and exercise test in medically treated patients with coronary artery disease.

To identify predictors of mortality in medically treated patients with symptomatic coronary artery disease, 30 variables were analyzed in 4,083 patients. Regression analysis demonstrated that seven variables were independent predictors of survival. A high risk subgroup (annual mortality rate above 5%) was identified, consisting of patients with either a congestive heart failure score of 3 to 4 or 1 mm or greater ST segment depression and final exercise stage of 1 or less. When all 30 variables were analyzed conjointly, the left ventricular contraction pattern (p less than 0.0001) and the number of diseased coronary vessels (p less than 0.003) proved to be the most important predictors of survival. In a subgroup of 572 patients with three vessel coronary disease and preserved left ventricular function, the probability of survival at 4 years ranged from 53% for patients only able to achieve stage 1/2 of exercise to 100% for patients able to exercise into stage 5 (p less than 0.004). Thus, in patients with defined coronary pathoanatomy, clinical and exercise variables primarily relating to the functional state of the left ventricle are helpful in assessing prognosis.

Adult↗
PubMed1984

Plasma verapamil levels and exercise performance.

Our study in 10 patients with stable, exercise-related angina under a double-blind, placebo-controlled protocol correlated plasma verapamil levels after single oral doses of 120 and 240 mg and exercise performance. Plasma verapamil levels peaked at 2 hr in seven patients and 4 hr in three patients and declined thereafter, with a mean plasma t1/2 of 3.22 and 4.54 hr after the 120- and 240-mg dose. Despite the relatively short t1/2s, total exercise duration and time to onset of angina and S-T segment depression were longer than placebo values for 4 hr after the 120-mg dose and for 8 hr after the 240-mg dose. Percentage increase in treadmill time and log of plasma verapamil levels correlated. All patients with plasma levels above 100 ng/ml had at least a 50% increase in exercise duration. Thus measurement of plasma verapamil levels are useful in patients who fail to respond to a dose of verapamil. If the level is below 100 ng/ml, increasing the dose of verapamil may improve response.

Administration, Oral↗
PubMed1984

Aortofemoral or femoropopliteal revascularization? A prospective evaluation of the papaverine test.

Proper selection of suprainguinal vs. infrainguinal arterial revascularization in patients with multilevel disease requires hemodynamic assessment. In such patients hemodynamic evaluation of the aortoiliac system cannot be made accurately with either arteriography or current noninvasive techniques. One hundred six lower extremities underwent preoperative triplane arteriography, measurement of Doppler-derived segmental blood pressures, measurement of common femoral intra-arterial pressure, and intra-arterial injection (30 mg) of the vasodilator papaverine hydrochloride prior to arterial bypass. Common femoral intra-arterial pressure was monitored continuously before and after papaverine injection. The resting femoral/brachial pressure index (FBI) and the maximum change in this index (% delta FBI) following papaverine injection were calculated. To be considered improved postoperatively, claudicants required an increase in treadmill walking time of greater than or equal to 50%, whereas patients operated on for limb salvage required an increase in the thigh/brachial pressure index (TBI) of greater than or equal to 0.15 for suprainguinal revascularizations and an increase of TBI to greater than or equal to 0.9 for infrainguinal revascularizations. In the first 41 extremities (phase I), receiver operator characteristic analysis revealed a % delta FBI greater than or equal to 15% to be optimal in the detection of hemodynamically significant aortoiliac disease. In phase II (65 limbs) this discriminant value for % delta FBI was assessed prospectively. In phase I, in which the choice of supra- vs. infrainguinal bypass was determined arteriographically, only 80% of the extremities were improved; in phase II, in which supra- vs. infrainguinal bypass was determined by the papaverine test, 98% of extremities were improved (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta↗
PubMed1984

A study of uniaxial tension on the superficial dermal microvasculature.

A spring-loaded apparatus was designed to apply uniaxial tension to forearm skin in 17 human subjects--10 normals, 6 psoriatics, and 1 patient with scleroderma. Simultaneously, the effects of stretching on the upper dermal vasculature were observed stereomicroscopically. Progressive changes (collapse) in the superficial microvasculature--vertical capillary loops and horizontal subpapillary plexus--with increasing tension were photographed. Force and strains were recorded at the points of disappearance of virtually all vessels. An average force of 11.9 newtons (N), accompanied by a mean strain of 10.3%, resulted in occlusion of all vessels. A much higher force (18.5 N) was necessary to occlude blood flow in the 1 patient with scleroderma. In summary, we have described a new technique for the study of mechanical forces on the blood supply of the epidermis. The data have shown that uniaxial tension has important effects on the superficial dermal microvasculature, resulting in impedance and obliteration of blood flow at relatively low magnitudes.

Adolescent↗