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Biomedical subjects

P Ganz

Publications and source records attributed to P Ganz.

At least 109 records · Page 6Linked to original sources
PubMed1991

Cancer control and the older person. Psychosocial issues.

Three major areas related to psychosocial issues pertinent to the provision of cancer control services to older people have been delineated. These are values and medical decision making, psychosocial barriers to screening and access to care and services, and quality of life, including rehabilitation. These areas are explored, salient issues are defined, and specific questions and areas for consideration in future research are identified at the macro and micro levels.

Age Factors↗
PubMed1991

The effect of atherosclerosis on the vasomotor response of coronary arteries to mental stress.

BACKGROUND: Mental stress can cause angina in patients with coronary artery disease, but its effects on coronary vasomotion and blood flow are poorly understood. Because atherosclerosis affects the reactivity of coronary arteries to various stimuli, such as exercise, we postulated that atherosclerosis might also influence the vasomotor response of coronary arteries to mental stress. METHODS: We studied 26 patients who performed mental arithmetic under stressful conditions during cardiac catheterization. (An additional four patients who did not perform the mental arithmetic served as controls.) Coronary segments were classified on the basis of angiographic findings as smooth, irregular, or stenosed. In 15 of the patients without focal stenoses in the left anterior descending artery, acetylcholine (10(-8) to 10(-6) mol per liter) was infused into the artery to test endothelium-dependent vasodilation. Changes in coronary blood flow were measured with an intracoronary Doppler catheter in these 15 patients. RESULTS: The response of the coronary arteries to mental stress varied from 38 percent constriction to 29 percent dilation, whereas the change in coronary blood flow varied from a decrease of 48 percent to an increase of 42 percent. The direction and magnitude of the change in the coronary diameter were not predicted by the changes in the heart rate, blood pressure, or plasma norepinephrine level. Segments with stenoses (n = 7) were constricted by a mean (+/- SE) of 24 +/- 4 percent, and irregular segments (n = 20) by 9 +/- 3 percent, whereas smooth segments (n = 25) did not change significantly (dilation, 3 +/- 3 percent; P less than 0.0002). Coronary blood flow increased by 10 +/- 10 percent in smooth vessels, whereas the flow in irregular vessels decreased by 27 +/- 5 percent. The degree of constriction or dilation during mental stress correlated with the response to the infusions of acetylcholine (P less than 0.0003, r = 0.58). CONCLUSIONS: Atherosclerosis disturbs the normal vasomotor response (no change or dilation) of large coronary arteries to mental stress; in patients with atherosclerosis paradoxical constriction occurs during mental stress, particularly at points of stenosis. This vasomotor response correlates with the extent of atherosclerosis in the artery and with the endothelium-dependent response to an infusion of acetylcholine. These data suggest that in atherosclerosis unopposed constriction caused by a local failure of endothelium-dependent dilation causes the coronary arteries to respond abnormally to mental stress.

Acetylcholine↗
PubMed1991

Nonclassical hydrophobic effect in membrane binding equilibria.

The enthalpy of transfer of four different amphiphilic molecules from the aqueous phase to the lipid membrane was determined by titration calorimetry. The four molecules investigated were the potential-sensitive dye 2-(p-toluidinyl)naphthalene-6-sulfonate (TNS), the membrane conductivity inducing anion tetraphenylborate (TPB), the Ca2+ channel blocker amlodipine [Bäuerle, H. D., & Seelig, J. (1991) Biochemistry 30, 7203-7211], and the positively charged local anesthetic dibucaine. All four amphiphiles penetrate into the hydrophobic part of the membrane, and their binding constants, after correcting for electrostatic effects, range between 600 M-1 for dibucaine and 60,000 M-1 for tetraphenylborate. The corresponding changes in free energy were about -6 to -9 kcal/mol. Binding of the amphiphiles to membrane vesicles composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine was accompanied by exothermic heats of reaction for all four molecules. For TNS, TPB, and amlodipine, the enthalpies of transfer were almost identical and corresponded to delta H approximately -9 kcal/mol, essentially accounting for the total free energy change. Thus, the binding of these charged amphiphiles to the hydrophobic membrane was driven by enthalpy. This is in contrast to the classical hydrophobic effect, where the transfer is considered to be entropy driven. For dibucaine, the enthalpy of transfer was smaller with delta H approximately -2 kcal/mol but was still about one-third of the total free energy change. All enthalpies of transfer exhibited a distinct temperature dependence with molar heat capacities delta Cp of -30 to -100 cal mol-1K-1 for the transfer from water to the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Amlodipine↗
PubMed1991

Patterns of care related to age of men with prostate cancer.

A chart review study was done of 242 Stages A2 to D1 cancer patients to determine whether the age of patients with prostate cancer influenced their physicians' management strategies. Ten hospitals of varying size, medical-school affiliation, and patient socioeconomic status participated in this study. Patterns of prostate cancer care were examined using sets of branching logic standards in the form of criteria maps. A chart-based comorbidity index was used to control for the effect of coexisting diseases on cancer management. Regression models indicated that patient age affected the intensity of both the diagnostic evaluation and therapy, even after controlling for independent factors such as comorbid disease and individual hospital differences. Patients aged 75 years and older had significantly less intensive clinical staging workups and use of surgical and radiation therapies compared with patients aged 65 to 74 years and patients aged 50 to 64 years. In conjunction with similar results noted in studies of elderly patients with other malignancies, these results suggest that age bias is likely to be widespread. Physicians need to consider life expectancy, the ability of the patient to tolerate diagnostic procedures and therapies, and the quality of life in making treatment decisions.

Age Factors↗
PubMed1991

Successful treatment of an excimer laser-associated coronary artery perforation with the Stack perfusion catheter.

A 64-year-old woman underwent excimer laser angioplasty of the right coronary artery. The procedure was complicated by perforation, which was successfully managed without complication with a Stack perfusion catheter. This report describes successful nonsurgical treatment of laser-induced coronary perforation and makes recommendations for avoiding this complication in other patients.

Angioplasty, Laser↗
PubMed1991

Effective aortic regurgitant orifice area: description of a method based on the conservation of mass.

The natural history of aortic regurgitation is incompletely understood in part because of the lack of a simple method to estimate the defect size. A method of determining the effective regurgitant orifice area that combines Doppler catheter and Doppler echocardiographic techniques and is based on the principle of conservation of mass (the continuity equation) is described. To validate the application of the Doppler catheter system for measuring regurgitant supravalvular diastolic flow, an in vitro model of retrograde aortic flow was used. These studies indicated that measurements of supravalvular retrograde velocity with the Doppler catheter accurately reflect retrograde diastolic velocity when the aorta is less than 4.8 cm in diameter. Twenty-three patients undergoing cardiac catheterization were studied; 20 of these patients had aortic regurgitation. Retrograde supravalvular diastolic velocity was determined from a Doppler catheter positioned above the aortic valve. The effective regurgitant orifice area was calculated with use of the Doppler catheter-derived regurgitant volume and mean transvalvular diastolic velocity as determined by either catheterization or continuous wave Doppler echocardiography. The catheterization-derived regurgitant orifice area increased with the angiographic grade of as follows: 1+ (0.04 to 0.10 cm2), 2+ (0.15 to 0.49 cm2), 3+ (0.29 to 1.11 cm2) and 4+ (1.24 to 1.33 cm2). By combining Doppler catheter, echocardiographic and cardiac catheterization techniques, the effective aortic regurgitant orifice area may be estimated; this hydrodynamic area correlates with grading by supravalvular aortography. Calculation of this area provides a quantitative alternative to aortography for estimating the severity of aortic regurgitation but should be used with caution in patients with a markedly dilated aorta.

Aortic Valve Insufficiency↗
PubMed1991

Hypercholesterolemia enhances macrophage recruitment and dysfunction of regenerated endothelium after balloon injury of the rabbit iliac artery.

BACKGROUND: We studied the effects on and possible interaction of balloon denudation and hypercholesterolemia on large arteries in the rabbit with special regard to structure and vascular reactivity. METHODS AND RESULTS: New Zealand White rabbits fed a 1% cholesterol diet or a standard diet for 14 weeks underwent balloon denudation of the left iliac artery 4 weeks before death. Both the balloon-injured and the control iliac arteries were harvested for in vitro studies of vascular reactivity, for immunohistochemical staining with monoclonal antibodies directed at smooth muscle cells and macrophages, and for scanning electron microscopy. Balloon injury caused intimal smooth muscle proliferation with little macrophage infiltration and was followed by recovery of endothelium-dependent vasodilator function within 4 weeks. Hypercholesterolemia caused macrophage-rich lesions confined to the intima with moderate impairment of endothelial vasodilator function. Balloon injury in the setting of hypercholesterolemia caused intimal smooth muscle cell proliferation and intense macrophage infiltration throughout the arterial wall and severe impairment of endothelial vasodilator function. Scanning electron microscopy confirmed regrowth of the endothelium in all balloon-injured vessels. In the balloon-injured arteries of hypercholesterolemic animals, the regenerated endothelium exhibited areas of atypical morphology not seen after balloon injury or hypercholesterolemia alone. CONCLUSIONS: The present study shows that balloon injury, hypercholesterolemia, and their combination cause distinct lesions and functional disturbances. An arterial balloon injury in the setting of hypercholesterolemia produces a diffuse inflammatory response that is accompanied by a sustained impairment of endothelial function and a marked proliferative response.

Animals↗
PubMed1991

Loss of flow-mediated endothelium-dependent dilation occurs early in the development of atherosclerosis.

BACKGROUND: Healthy arteries exhibit endothelium-dependent dilation in response to both local acetylcholine and increased blood flow. In humans, clinically overt coronary artery disease is characterized by loss of dilation to both acetylcholine and blood flow. The temporal relation, however, between functional abnormalities of the endothelium and the development of atherosclerosis has not been established. METHODS AND RESULTS: We examined endothelial vasodilator function in vivo at an early stage of the development of atherosclerosis. Two groups of seven Macaca fascicularis monkeys were studied; one group was fed a high cholesterol diet (0.73-1.0 mg cholesterol per calorie) for 11 months. Cholesterol feeding was associated with increased plasma cholesterol levels and with intimal thickening of the iliac arteries but with no reduction in luminal diameter. Endothelium-dependent vasomotor responses of the iliac arteries were then examined in vivo by quantitative contrast angiography. Acetylcholine produced significant dilation in the controls but paradoxical constriction in the group with early atherosclerosis (+9.0 +/- 3.2% versus -5.3 +/- 5.4%, p less than 0.05). In response to a twofold increase in blood flow achieved by administering adenosine distal to the arterial segment under examination, the controls again dilated, whereas the atherosclerotic group failed to dilate (+ 11.6 +/- 2.1% versus + 0.5 +/- 2.4%, p less than 0.05). Both groups, however, were able to dilate, and dilated equally, to the nonendothelium-dependent agent nitroglycerin (+ 13.7 +/- 4.8% versus + 19.1 +/- 4.3%, NS). CONCLUSIONS: Endothelium-dependent vasodilation in response to both acetylcholine and increased blood flow may be lost early in the course of developing atherosclerosis before the appearance of stenosing and occlusive disease.

Acetylcholine↗
PubMed1991

Diurnal rhythms and clinical events in coronary artery disease.

Patients with coronary atherosclerosis present with angina, myocardial infarction and sudden death, most often caused by atherosclerotic stenosis complicated by spasm and/or occlusive thrombosis. All of these events have been shown to exhibit similar diurnal rhythms, with a peak incidence in the morning after waking and rising. Other cardiovascular parameters also show a similar diurnal rhythm associated with increased sympathetic outflow and circulating catecholamines, producing increases in heart rate, blood pressure, myocardial contractility and oxygen demand soon after waking and rising. Experimental and clinical research has recently pointed to several possible mechanisms that might be responsible for these events. In patients with atherosclerosis, dysfunction of the endothelium in the epicardial coronary arteries results in a failure to limit the constrictor response to catecholamines. Catecholamines can also alter the procoagulant nature of vascular surfaces. We speculate that the interaction between increased sympathetic activity and the procoagulant and vasoconstrictor states of atherosclerotic coronary stenoses may lead to a lower threshold to ischaemia in the waking hours, with a corresponding increase in angina, myocardial infarction and sudden death. These factors may be important considerations for the selection of suitable therapies and for future research.

Cardiovascular System↗
PubMed1990

Large coronary arteries in humans are responsive to changing blood flow: an endothelium-dependent mechanism that fails in patients with atherosclerosis.

Changes in blood flow can alter vasomotion of conduit arteries. This study examined vasomotor responses to incremental blood flow induced by papaverine in the epicardial arteries of 10 patients with angiographically normal coronary arteries (group 1) and in 14 patients with arterial irregularities (group 2) using quantitative angiography and Doppler ultrasound flow velocity measurements. An increase in coronary blood flow of 384.3 +/- 32.8% (p less than 0.001) in group 1 patients was associated with dilation of the proximal coronary artery segment and a 23.2 +/- 4.6% increase in cross-sectional area (p less than 0.001). In contrast, in group 2 patients a similar increase in coronary blood flow of 339.3 +/- 18.7% (p less than 0.001) was associated with mixed responses and a modest net constriction in cross-sectional area of -7.4 +/- 2.8% (p less than 0.05). The dilation response to nitroglycerin was intact in group 1 (31.7 +/- 4.2%, p less than 0.001) and in group 2 (26.4 +/- 3.2%, p less than 0.001). In five patients from group 1 acetylcholine, an endothelium-dependent dilator, produced an increase in cross-sectional area of 20.7 +/- 4.6% (p less than 0.05) that paralleled the response to an increase in flow in the same segment (a 24.3 +/- 6.1% increase in cross-sectional area, p less than 0.05). Five group 2 patients demonstrated a vasoconstrictor response to acetylcholine (a -22.8 +/- 3.4% decrease in cross-sectional area, p less than 0.05) together with an impaired dilation response to incremental flow (a -6.4 +/- 3.2% decrease in cross-sectional area).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1990

Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease.

In animals, acetylcholine dilates normal arteries and produces vasoconstriction in the presence of hypercholesterolemia, hypertension, or atherosclerosis, reflecting endothelial cell dysfunction. In patients with angiographically smooth coronary arteries, acetylcholine has been reported to produce both vasodilation and constriction. To test the hypothesis that the acetylcholine response relates to risk factors for coronary artery disease, acetylcholine 10(-8) to 10(-6) M was infused into the left anterior descending or circumflex coronary artery, and diameter changes were assessed with quantitative angiography in 34 patients with angiographically smooth coronary arteries. The acetylcholine response ranged from +37% (dilation) to -53% (constriction) at the peak acetylcholine dose. All coronary arteries dilated in response to nitroglycerin (26 +/- 17%), suggesting an abnormality of endothelial function in the patients with a constrictor response to acetylcholine. By multiple stepwise regression analysis, serum cholesterol (p less than 0.01), male gender (p less than 0.001), family history (p less than 0.05), age (p less than 0.05), cholesterol level (p less than 0.01), and total number of risk factors (p less than 0.0001) were independently associated with the acetylcholine response. Thus, coronary risk factors are associated with loss of endothelium-dependent vasodilation. The development of vasoconstriction is likely to be an abnormality of endothelial function that precedes atherosclerosis or an early marker of atherosclerosis not detectable by angiography.

Acetylcholine↗
PubMed1990

Paradoxical narrowing of atherosclerotic coronary arteries induced by increases in heart rate.

Vasodilation in normal and vasoconstriction in atherosclerotic coronary arteries have been observed in response to complex stimuli such as exercise and the cold pressor test. To study a single parameter that changes during these activities, and to better understand the pathophysiology of ischemia associated with increases in heart rate, we studied coronary vasomotion and blood flow response to increasing heart rate alone, produced by atrial pacing, with quantitative angiographic and Doppler flow-velocity measurements in 15 patients. In five patients with angiographically smooth coronary arteries (group 1), tachycardia produced progressive dilation of the epicardial artery with increases in cross-sectional area (CSA) of +15.5 +/- 3.4%, +22.4 +/- 2.1%, +28.5 +/- 3.3%, and +30.6 +/- 2.2% at 90, 110, 130, and 150 beats/min, respectively. In contrast, in five patients with mild angiographic narrowings (group 2), coronary segments failed to dilate with progressive tachycardia (-6.3 +/- 2.0%, -8.3 +/- 2.0%, -12.5 +/- 2.0%, and -11.4% at 90, 110, 130, and 150 beats/min, respectively), and progressive loss of luminal area was observed in five patients with severe angiographic narrowings (group 3) (-34.4 +/- 3.4%, -49.6 +/- 2.2%, -59.2%, and -72.8% at 90, 110, 130, and 150 beats/min, respectively). Coronary blood flow increased significantly with tachycardia in group 1 (+44.5 +/- 10.2%, +86.0 +/- 24.6%, +105.8 +/- 29.3%, and +137.5 +/- 46.0%), increased slightly in group 2 (+7.8 +/- 3.2%, +9.4 +/- 4.4%, +8.4 +/- 3.9%, and +10.0%), and decreased significantly in group 3 (-31.8 +/- 6%, -42.6 +/- 10.7%, -61.0%, and -70.0%). We conclude that an isolated increase in heart rate in patients with normal coronary arteries results in a modest increase in flow and vasodilation. In early atherosclerosis, the flow increase is blunted and dilation is replaced with paradoxical loss in luminal size. In patients with stenoses, further loss in luminal size occurs accompanied by a decrease in coronary blood flow. Thus, increasing heart rate alone in the setting of coronary stenoses could produce myocardial ischemia by a reduction in coronary supply, as well as by an increase in oxygen demand.

Aged↗