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Biomedical subjects

T J Ryan

Publications and source records attributed to T J Ryan.

At least 217 records · Page 12Linked to original sources
PubMed1990

Revascularization for acute myocardial infarction. Strategies in need of revision.

Prompt reperfusion of the ischemic myocardium by the successful use of thrombolytic agents in the setting of acute myocardial infarction has substantially reduced mortality among patients judged eligible for their use. This approach has revolutionized the management of acute infarction patients worldwide. Such therapy, however, is associated with increased rates of reinfarction and postinfarction angina that have been attributed to the underlying residual atherosclerotic lesion. The expectation that coronary angioplasty would provide the logical solution to this clinical problem has been considerably lowered by the results of a number of prospective randomized clinical trials. These findings, coupled with the realization that as many as 50% of patients suffering acute infarctions will not safely qualify for the use of thrombolytic agents, present compelling reasons to more accurately investigate the role of primary angioplasty and bypass surgery as a means of effecting reperfusion therapy in the setting of acute infarction.

Acute Disease↗
PubMed1990

Grip and stick and the lymphatics.

Kaposi sarcoma is a common, though not inevitable consequence of AIDS. There is a body of opinion that believes that this sarcoma is derived from lymphatic endothelium, or at least from a failure of vascular endothelium to distinguish between whether it is attempting to be a blood vessel or a lymphatic. While immunodeficiency and its consequences have proved to be the most significant area of research, the general biology of endothelium, and especially angiogenesis, has perhaps been neglected. I predict that the most important new concept in the biology of endothelium is the recognition of mechanico-receptors as a determinant of its behavior. The concept is illustrated by articles from Oxford (Ryan 1989), from Boston, Massachusetts (Ingber & Folkman 1989), and from Moscow (Shirinsky et al 1989). Most authors studying endothelium have concentrated on blood vascular endothelium and ignored the rich lymphatic bed. Since the lymphatic is par excellence a mechanical receptor, this is perhaps surprising. The lymphatic functions by its responsiveness to mechanical forces, it is a fine control for hydrostatic pressure within the interstitium, and morphologically, its flat and attenuated endothelium linked to strong anchoring fibers is biologically exactly the kind of behavior required of a cell that is responsive to mechanical factors. Perhaps the best known mechanical receptor is the stretch receptor in the muscle fiber. The linkage of this receptor to the enzyme protein kinase C has been described. Ryan has also pointed out that protein kinase C may be an important mechanico-receptor in the fibroblast and possibly also universally in all cells, including lymphatic endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1989

Factors predicting recurrent restenosis after percutaneous transluminal coronary balloon angioplasty.

To identify factors that predict a second restenosis after repeat percutaneous transluminal coronary balloon angioplasty (PTCA), the records of 196 consecutive patients undergoing redilation for treatment of a first restenosis were reviewed. Repeat PTCA was successful in 181 (92%) of these patients. After a successful second PTCA, 47 patients (26%) developed a second restenosis (recurrent restenosis group, group 1) and 134 (single restenosis group, group 2) did not. The 2 patient groups were compared with respect to clinical, angiographic and procedural factors at second PTCA. Univariate correlates of a second restenosis were younger age (54 +/- 10 vs 57 +/- 9 years, p less than 0.05), interval less than 60 days between initial PTCA and recurrence of anginal symptoms (55% of patients in group 1 vs 25% in group 2, p = 0.001), a greater number of inflations (6.3 +/- 4.2 vs 4.4 +/- 2.5, p less than 0.005) and a shorter maximal balloon inflation time (49 +/- 26 vs 69 +/- 36 seconds, p = 0.0006). With multivariate analysis, the 2 factors that emerged as independent predictors of recurrent restenosis were recurrence of symptoms less than 60 days after initial PTCA (p less than 0.004) and a greater number of inflations (p less than 0.04). These data suggest that younger age and rapid recurrence of anginal symptoms after first PTCA predict an increased likelihood that a second restenosis will occur after repeat PTCA and that certain procedural factors, in particular the greater number of balloon inflations and a shorter maximal balloon inflation time, may play an important role in the development of recurrent restenosis.

Angioplasty, Balloon↗
PubMed1989

The role of exercise-induced silent myocardial ischemia in patients with abnormal left ventricular function. A report from the Coronary Artery Surgery Study (CASS) registry.

To evaluate the significance of ischemic ST depression without anginal chest pain (silent ischemia) during exercise testing among patients with abnormal left ventricular function, the data on 121 such patients with proven coronary artery disease (CAD) from the Coronary Artery Surgery Study (CASS) registry were analyzed. The patients with silent ischemia (group 1) were compared to: 124 CAD patients with both ST depression and angina (symptomatic ischemia, group 2); 159 CAD patients with neither ST depression nor angina (no ischemia, group 3); and 37 patients without CAD (controls). Survival at 7 years with medical therapy was similar for groups 1 (55%) and 2 (60%), but was substantially better for group 3 (73%, p = 0.001). Among group 1 patients with silent ischemia, survival was related to the severity of CAD (p = 0.001). Patients with silent ischemia and three-vessel CAD had a poor 7-year survival rate (37%) when treated medically. A comparable but non-randomized group of patients with silent ischemia and three-vessel CAD who underwent coronary artery bypass surgery had a much better 7-year survival rate (83%, p less than 0.0001). These results suggest that among patients with CAD and abnormal left ventricular function, silent ischemia adversely affects survival and can identify a higher risk subset of patients whose survival might be improved after coronary bypass surgery.

Coronary Disease↗
PubMed1989

Effect of arginine vasopressin on coronary and systemic hemodynamics in man.

Arginine vasopressin is a potent constrictor of isolated arterial segments in vitro. However, it is disputed whether, in vivo, arginine vasopressin acts as either a systemic or coronary vasoconstrictor. The purpose of this study was to determine the effect of arginine vasopressin on coronary and systemic vascular tone in man. Six patients undergoing routine diagnostic cardiac catheterization were studied. At angiography, all patients were found to have severe coronary artery disease. Cardiac and systemic pressures and coronary blood flow as well as serum arginine vasopressin and osmolality levels were measured before and after administration of hypertonic contrast dye and then following intravenous injection of an analog inhibitor of arginine vasopressin. At baseline, serum arginine vasopressin levels were within the normal range in all patients, but, following infusion of contrast dye, rose above physiological levels in 5 patients. In these latter patients, there were no significant changes in coronary and systemic hemodynamics between baseline (condition 1), following administration of contrast dye (condition 2) and 10 minutes after injection of arginine vasopressin inhibitor (condition 3). Mean coronary sinus blood flow (ml/min) and mean coronary vascular resistance (dyne.sec.cm-5) were 184 +/- 49 and 41,235 +/- 8275 during condition 1, 204 +/- 62 and 39,442 +/- 8781 during condition 2, and 192 +/- 75 and 44,930 +/- 11455 during condition 3. Mean arterial pressure (mm Hg) and mean systemic vascular resistance (dyne.sec.cm-5) during conditions 1, 2 and 3 were 105 +/- 12 and 1454 +/- 174, 114 +/- 21 and 1432 +/- 210, and 114 +/- 15 and 1436 +/- 147, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Antecedent angina: a predictor of residual stenosis after thrombolytic therapy.

Patients with a significant residual stenosis after thrombolytic therapy are believed by many to be at increased risk for repeat ischemic events and may be candidates for prompt angiography and revascularization. To test the hypothesis that patients with antecedent angina (Canadian classes I to IV, greater than or equal to 24 h before myocardial infarction) are more likely to have a significant residual stenosis (greater than or equal to 60% diameter reduction) than are those without antecedent angina, the coronary angiograms of 82 consecutive patients undergoing routine angiography after thrombolytic therapy were reviewed. Compared with the patients without antecedent angina, the group with antecedent angina had an increased mean stenosis (74% versus 58%) and more multivessel disease (44% versus 5%). The sensitivity and specificity of a clinical history of antecedent angina predicting the presence of a significant residual stenosis were 75% and 96%, respectively; the positive predictive accuracy was 98%. These data suggest that antecedent angina can be used to identify a high risk subgroup whose condition may warrant routine coronary angiography.

Angina Pectoris↗
PubMed1989

Biochemical consequences of mechanical forces generated by distention and distortion.

This review includes a number of concepts: (1) mechanical forces are transmitted to cell membranes by adhesion complexes between solid elements in the extracellular environment and the cytoskeleton; (2) the adhesion complexes require inhibition of proteases to maintain their adhesion; and (3) hydrostatic pressure is a mechanical stress on solid elements in the tissues, and it is controlled by the microcirculation and lymphatic system. Hypotheses include the following: (1) mechanical forces act on the cell membrane and induce inhibitors of proteases, thereby maintaining the adhesion complexes; (2) the transduction of chemical signals--protease inhibition--is more flexible in young cells, wounds, and psoriasis. In old tissues, protease inhibition is more sustained; and (3) cell shape, cell migration, and mitosis are in part controlled by such mechanisms. These hypotheses are supported by evidence from the literature and observations from my experience and that of many co-workers in the fields of microcirculation, lymphatic systems, angiogenesis, wound healing, and proteases.

Biochemical Phenomena↗
PubMed1989

Structure and function of lymphatics.

Lymphatics are large vessels with a lumen potentially ten times wider than blood vessels and have a mean mesh diameter in the upper dermis of approximately 504 +/- 88 microns. The plexus lies just deep to the subpapillary venous plexus and when functioning well it is difficult to identify because of the attenuated endothelium and collapsed lumen. The role of the lymphatic as a pathway for the Langerhans cell and as an exit for macromolecules such as lipid and protein make it an essential organ for normal skin biology. When this system fails, impaired immunity, fibrosis, and recurrent infections are inevitable. Even vasculitis may be a consequence of failure of clearance of immune complexes from the interstitium. The adipose tissue and deep dermis are especially vulnerable in this respect. Elastin fibers support cutaneous lymphatics and may be low resistance pathways through the connective tissues into the lymphatic. Identification of lymphatics by special markers is a concept that currently fails to take into account that changing roles in disease may be associated with a change in the specificity of markers. The anatomy of lymphatic vessels in the skin is described and the role of the lymphatic is emphasized.

Anions↗
PubMed1989

Darier's disease: an immunohistochemical study using antibodies to proteases.

The expression of plasminogen activators, plasminogen and fibrinogen was investigated in 10 specimens of normal skin and in the involved skin of seven males with Darier's disease, using immunohistochemical techniques. Changes in the localization of proteases were found in the involved skin of Darier's disease, plasminogen being expressed by suprabasal cells and fibrinogen being detected in the keratotic plug.

Darier Disease↗
PubMed1989

Outcome in patients with recurrent restenosis after percutaneous transluminal balloon angioplasty.

The records of 1162 consecutive patients undergoing their first percutaneous transluminal coronary angioplasty at a centre between March 1980 and June 1987 were reviewed. Initial angioplasty was successful in 1011 patients (87%). In 202 (20%) symptomatic restenosis developed. Of these, 196 were treated with redilatation; this was successful in 181 (92%). After a second dilatation, restenosis developed in 47 patients (26%). Of these, 41 (87%) were treated with a third angioplasty, with primary success in 38 (93%). A further restenosis developed in 13 of these 38 patients (34%). Eight patients were treated with a fourth angioplasty with restenosis in four (50%). Two of these four patients underwent a fifth angioplasty (with continuing success at long term follow up in both). Overall, 14 of the 47 (30%) patients who developed restenosis twice were eventually treated with coronary bypass surgery. Most patients (33), however, were treated only with repeated angioplasties. Of these 33 patients, 27 were treated with a third angioplasty, four with a fourth procedure, and two with a fifth. Twenty-nine (88%) were symptom free at a mean follow up of 28 (range 8 to 86) months. The combined success rate for a third, fourth, and fifth angioplasty was 94%. These data suggest that most patients with recurrent restenosis after angioplasty may be managed successfully and safely with repeated redilatations.

Adult↗
PubMed1989

Role of catalytic and lysine-binding sites in plasmin-induced neutrophil adherence to endothelium.

Plasmin resulted in increased neutrophil adherence to cultured ovine pulmonary artery endothelial cell monolayers in a concentration-dependent manner (10(-12)-10(-7) M). The adherence response increased fivefold above baseline within 60 min after addition of plasmin (10(-8) M) and the response persisted up to 30 min after removal of plasmin. The neutrophil adherence was mediated by the action of plasmin on neutrophils rather than endothelial cells. The response was the result of an increase in functional activity of CD18 neutrophil cell surface adhesive glycoprotein. Neutrophil adherence was inhibited by pretreatment of neutrophils with MAbs IB4 and 60.3 targeted against the beta chain of the CD18, whereas control isotypic MAb 60.5 against HLA class I antigen had no effect. The plasmin catalytic site was not involved in the response. Lys-plasminogen had reduced adherence-promoting activity relative to plasmin, whereas glu-plasminogen had no effect. Elastase-derived plasminogen fragments corresponding to kringle 1+2+3 and kringle 4 (both of which contained the lysine-binding sites) possessed neutrophil adherence-promoting activities similar to plasmin, whereas miniplasminogen (which contains the catalytic site but no lysine-binding sites) had minimal effect, indicating the involvement of lysine-binding sites in the response. Blocking lysine-binding sites of plasmin and elastase-derived plasminogen fragments with tranexamic acid (IC50 of 5 mM) inhibited neutrophil adherence. A monospecific polyclonal antibody against the lysine-binding sites also reduced the neutrophil adherence-promoting activity of plasmin. The results indicate that plasmin induces neutrophil adherence to the endothelium and that the effect is mediated by lysine-binding sites on plasmin.

Animals↗
PubMed1989

Improved survival of surgically treated patients with triple vessel coronary artery disease and severe angina pectoris. A report from the Coronary Artery Surgery Study (CASS) registry.

We examined survival rates during a 6-year follow-up of patients in the registry of the Coronary Artery Surgery Study who had three vessel coronary artery disease and Canadian Cardiovascular Society class III-IV angina pectoris. All patients had a stenosis of 70% or greater in either the mid or proximal segment of all three coronary arteries. There were 679 medically treated patients and 1921 surgically treated patients in this nonrandomized comparison. Patients were stratified by left ventricular wall motion score and number of proximal coronary artery stenoses; after adjustment for these variables, the estimated probability of being alive at 6 years was 82% for surgically treated patients and 59% for medically treated patients (p less than 0.0001). Among patients with the most severe left ventricular dysfunction (left ventricular wall motion score of 16 to 30), the 6-year survival rate was 63% for surgically treated patients and 30% for medically treated patients (p less than 0.0001). Those with three proximal lesions (all gradations of left ventricular score) had an 81% 6-year survival rate with surgical treatment and 40% with medical treatment (p less than 0.0001). Ninety percent of surgically treated patients with normal ventricular function were living at 6 years and 78% of medically treated patients (p less than 0.0001). Among these patients, the survival rate was significantly better after surgical treatment than after only medical treatment if two or three proximal stenoses were present. If no proximal lesions were present (all categories of left ventricular function), 84% of surgically treated patients and 67% of medically treated patients were alive at 6 years (p less than 0.0001). In a multivariate (Cox) analysis of preoperative clinical, hemodynamic, and angiographic factors, early operation was a strong predictor of survival (estimated relative risk 0.38).

Actuarial Analysis↗