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Biomedical subjects

J H Chesebro

Publications and source records attributed to J H Chesebro.

At least 181 records · Page 10Linked to original sources
PubMed1984

Membranoproliferative glomerulonephritis. A prospective clinical trial of platelet-inhibitor therapy.

Forty patients with Type I membranoproliferative glomerulonephritis were treated for one year with dipyridamole, 225 mg per day, and aspirin, 975 mg per day, in a prospective, randomized, double-blind, placebo-controlled study. At the base line, the half-life of 51Cr-labeled platelets was reduced in 12 of 17 patients. The platelet half-life became longer and renal function stabilized in the treated group, as compared with the placebo group, suggesting a relation between platelet consumption and the glomerulopathy. The glomerular filtration rate, determined by iothalamate clearance, was better maintained in the treated group (average decrease, 1.3 ml per minute per 1.73 m2 of body-surface area per 12 months) than in the placebo group (average decrease, 19.6). Fewer patients in the treated group than in the placebo group had progression to end-stage renal disease (3 of 21 after 62 months as compared with 9 of 19 after 33 months). The data suggest that dipyridamole and aspirin slowed the deterioration of renal function and the development of end-stage renal disease.

Adolescent↗
PubMed1984

Effect of dipyridamole and aspirin on late vein-graft patency after coronary bypass operations.

To study the prevention of occlusion of aortocoronary-artery bypass grafts, we concluded a prospective, randomized, double-blind trial comparing long-term administration of dipyridamole (begun two days before operation) plus aspirin (begun seven hours after operation) with placebo in 407 patients. Results at one month showed a reduction in the rate of graft occlusion in patients receiving dipyridamole and aspirin. At vein-graft angiography performed in 343 patients (84 per cent) 11 to 18 months (median, 12 months) after operation, 11 per cent of 478 vein-graft distal anastomoses were occluded in the treated group, and 25 per cent of 486 were occluded in the placebo group. The proportion of patients with one or more distal anastomoses occluded was 22 per cent of 171 patients in the treated group and 47 per cent of 172 in the placebo group. All grafts were patent within a month of operation in 94 patients in the placebo group and 116 patients in the treated group; late development of occlusions was reduced from 27 per cent in the placebo group to 16 per cent in the treatment group. The results show that dipyridamole and aspirin continue to be effective in preventing vein-graft occlusion late after operation, and we believe that such treatment should be continued for at least one year.

Adult↗
PubMed1984

Trial of platelet-inhibiting drug in scleroderma. Double-blind study with dipyridamole and aspirin.

In a randomized, double-blind, controlled study, 28 patients with early scleroderma received dipyridamole (225 mg/day) and aspirin (975 mg/day) or placebo for 1-2 years. No significant clinical or objective laboratory improvement was noted in either group. Platelet survival time, plasma renin activity, and coagulation tests were not predictive of disease course. Biomechanical and vascular tests of the hands correlated with clinical extent of skin induration and presence of finger ulcers, respectively.

Aspirin↗
PubMed1984

Intracellular calcium transients in human working myocardium as detected with aequorin.

The calcium transients associated with contraction in human working myocardium were recorded by use of the bioluminescent protein, aequorin, a substance that emits light when it combines with calcium ion (Ca++). Small amounts of aequorin were microinjected into superficial cells of human atrial and ventricular muscle obtained from tissue routinely excised and discarded at the time of cardiac surgery. Light output, an index of intracellular Ca++, and isometric tension development were recorded at 37.5 degrees C at 1 to 5 second intervals of stimulation. Light increases much more quickly than tension and decreases toward basal levels by the time that peak tension is reached. The configuration and time course of the aequorin signal in human myocardium and its responses to inotropic interventions are similar to those recorded in lower mammalian species. The calcium transient appears to be dominated by the release and uptake of Ca++ from intracellular stores under all conditions studied. These results indicate that aequorin is a useful tool for studying the effects of drugs and disease states on cardiac excitation-contraction coupling in human beings as well as in lower animals.

Aequorin↗
PubMed1983

New "ex vivo" radioisotopic method of quantitation of platelet deposition - studies in four animal species.

We have developed a sensitive and quantitative method of "ex vivo" evaluation of platelet deposition on collagen strips, from rabbit Achilles tendon, superfused by flowing blood and applied it to four animal species, cat, rabbit, dog and pig. Autologous platelets were labeled with indium-111-tropolone, injected to the animal 24 hr before the superfusion and the number of deposited platelets was quantitated from the tendon gamma-radiation and the blood platelet count. We detected some platelet consumption with superfusion time when blood was reinfused entering the contralateral jugular vein after collagen contact but not if blood was discarded after the contact. Therefore, in order to have a more physiological animal model we decided to discard blood after superfusion of the tendon. In all species except for the cat there was a linear relationship between increase of platelet on the tendon and time of exposure to blood superfusion. The highest number of platelets deposited on the collagen was found in cats, the lowest in dogs. Ultrastructural analysis showed the platelets were deposited as aggregates after only 5 min of superfusion.

Animals↗
PubMed1983

Trial of combined warfarin plus dipyridamole or aspirin therapy in prosthetic heart valve replacement: danger of aspirin compared with dipyridamole.

Despite the use of oral anticoagulation in patients with prosthetic heart valves, persistent thromboembolism over time warrants a search for improved methods of prevention. Thus, patients receiving 1 or more mechanical prosthetic heart valves were randomized to therapy with warfarin plus dipyridamole (400 mg/day) or warfarin plus aspirin (500 mg/day) on the basis of location and type of valve and surgeon, and followed up with a concurrent, nonrandomized control group taking warfarin alone. In 534 patients followed up 1,319 patient-years, excessive bleeding (necessitating blood transfusion or hospitalization) was noted in the warfarin plus aspirin group (23 of 170 [14%], or 6.0/100 patient-years) compared with warfarin plus dipyridamole (7 of 181 [4%], or 1.6/100 patient-years, p less than 0.001), or warfarin alone (9 of 183 [5%], or 1.8/100 patient-years, p less than 0.001). A trend was evident toward a reduction in thromboembolism in the warfarin plus dipyridamole group (2 of 181 [1%], or 0.5/100 patient-years) as compared with warfarin plus aspirin (7 of 170 [4%], or 1.8/100 patient-years), or warfarin alone (6 of 183 [4%], or 1.2/100 patient-years). Adequacy of anticoagulation (based on 12,720 prothrombin time determinations) was similar in all 3 groups with 65% of prothrombin times in the therapeutic range (1.5 less than or equal to prothrombin time/control less than or equal to 2.5), 30% too low, and 5% too high. Warfarin plus aspirin therapy resulted in excessive bleeding and is contraindicated. Longer follow-up study is needed to determine whether further separation of the incidence of thromboembolism can be detected.

Aspirin↗
PubMed1983

In vivo quantitation of platelet deposition on human peripheral arterial bypass grafts using indium-111-labeled platelets. Effect of dipyridamole and aspirin.

Indium-111-labeled autologous platelets, injected 48 hours after operation, were used to evaluate the thrombogenicity of prosthetic material and the effect of platelet inhibitor therapy in vivo. Dacron double-velour (Microvel) aortofemoral artery bifurcation grafts were placed in 16 patients and unilateral polytetrafluoroethylene femoropopliteal grafts were placed in 10 patients. Half the patients in each group received platelet inhibitors before operation (dipyridamole, 100 mg 4 times a day) and after operation (dipyridamole, 75 mg, and acetylsalicylic acid, 325 mg 3 times a day); the rest of the patients served as control subjects. Five-minute scintigrams of the graft region were taken with a gamma camera interfaced with a computer 48, 72, and 96 hours after injection of the labeled platelets. Platelet deposition was estimated from the radioactivities of the grafts and expressed as counts per 100 pixels per microcurie injected. Dipyridamole and aspirin therapy significantly reduced the number of platelets deposited on Dacron grafts and prevented platelet accumulation over 3 days. With the small amount of platelet deposition on polytetrafluoroethylene femoropopliteal artery grafts even in control patients, platelet inhibitor therapy had no demonstrable effect on platelet deposition on these grafts. It is concluded that (1) platelet deposition on vascular grafts in vivo can be quantitated by noninvasive methods, and (2) dipyridamole and aspirin therapy reduced platelet deposition on Dacron aortofemoral artery grafts.

Adult↗
PubMed1983

Comparison of the antithrombotic action of calcium antagonist drugs with dipyridamole in dogs.

Because platelet activation is associated with fluxes of intracellular calcium, calcium antagonist drugs such as verapamil and nifedipine may have useful platelet inhibitor effects. Accordingly, the effect of these drugs was compared with that of dipyridamole, an established platelet inhibitor, in preventing the deposition of indium-111-labeled autologous platelets and thrombus development in polytetrafluoroethylene (Gore-Tex) grafts interposed in both femoral arteries in mongrel dogs. Eight dogs received verapamil 7.5 micrograms/kg/min perioperatively, 8 dogs received nifedipine 4 micrograms/kg/h perioperatively, 8 dogs received dipyridamole 50 mg orally given twice during the 24 hours before operation, and 16 control dogs received isotonic saline solution perioperatively. After 3 hours of perfusion, the median weight of the grafts and luminal thrombus was less in dogs treated with dipyridamole (465.1 mg), verapamil (453.7 mg), or nifedipine (389.7 mg) than in control dogs (680.2 mg) (p less than 0.001). In addition, the estimated total platelet deposition along the graft was reduced in dogs treated with dipyridamole was reduced in dogs treated with dipyridamole (2,073.2 X 10(6)) (p less than 0.01), verapamil (1,898.9 X 10(6)) (p less than 0.001), and nifedipine (1,474.8 X 10(6)) (p less than 0.001) as compared with controls (3,056.2 X 10(6)). When the mural thrombus was removed from 14 grafts, a median 73% of the platelets were located in the interface between thrombus and graft. We conclude that all 3 drugs prevent thrombus formation by inhibiting platelet activity in this model, and that the calcium antagonist drugs are as effective as dipyridamole.

Animals↗
PubMed1982

A platelet-inhibitor-drug trial in coronary-artery bypass operations: benefit of perioperative dipyridamole and aspirin therapy on early postoperative vein-graft patency.

To prevent occlusion of aortocoronary-artery-bypass grafts, we conducted a prospective, randomized-double-blind trial comparing dipyridamole (instituted two days before operation) plus aspirin (added seven hours after operation) with placebo in 407 patients. Vein-graft angiography was performed in 360 patients (88 per cent) within six months of operation (median, eight days). Within one month of operation, 3 per cent of vein-graft distal anastomoses (10 of 351) were occluded in the treated patients, and 10 per cent (38 of 362) in the placebo group; the proportion of patients with one or more distal anastomoses occluded was 8 per cent (10 of 130) in the treated group and 21 per cent (27 of 130) in th placebo group. This benefit in graft patency persisted in each of over 50 subgroups. Early postoperative bleeding was similar in the two groups. In this trial dipyridamole and aspirin were effective in preventing graft occlusion early after operation.

Adult↗
PubMed1982

Strong family history and cigarette smoking as risk factors of coronary artery disease in young adults.

This study is based on 435 consecutive patients age 50 or less who had coronary arteriography. There were 335 patients with coronary artery disease and 100 with normal coronary arteries. Risk factors reviewed were "packet-years" of cigarette smoking, family history of coronary disease in first-degree relatives 50 years of age or less, age- and sex-corrected serum cholesterol and triglycerides, hypertension, and diabetes. By univariate analysis, each risk factor except hypertension and diabetes was significantly more frequent in patients with coronary disease than in those without. By multivariate analysis of all risk factors in patients with and without coronary disease, the male or female patient with coronary disease could best be identified by the strong family history, cigarette smoking history, and age- and sex-corrected serum cholesterol. The percentage of patients with coronary disease when the three risk factors were present was 95%, two factors present 88%, one factor present 67%, none of the three 25%, strong family history alone 90%, smoking alone 66%, and serum cholesterol greater than 80th centile alone 52%.

Adult↗
PubMed1982

Left ventricular performance before and after aortocoronary artery bypass surgery.

Left ventricular performance was studied before and late (mean 12-17 months) after aortocoronary artery bypass surgery by quantitative, computer-based videoangiography. We measured total function (left ventricular ejection fraction, volumes and end-diastolic pressure) at rest (in 60 patients) and before and after exercise (abnormal exercise hemodynamics preoperatively in 32 patients) and regional function (peak rate of systolic wall thickening) at rest (in 60 patients) and before and after administration of nitroglycerin (in 19 patients). Total left ventricular function at rest is usually unchanged postoperatively. Exercise hemodynamics are more sensitive indexes of performance and, if abnormal, usually improve postoperatively if revascularization has been complete and extensive myocardial infarction has not occurred. Regional myocardial function usually improves postoperatively if the bypass graft to the region is patent and has a blood flow of more than 60 ml/min (measured late postoperatively by videodensitometry) and if no previous infarction was present in the region. Myocardial infarction and graft blood flow of 40 ml/min or less are the two main factors that prevent improvement in abnormal regions defined by the regional wall thickening method when bypass grafts are patent. Regions supplied by occluded grafts show decreases in regional function. The preoperative wall-thickening response to administration of nitroglycerin can be used to distinguish ischemia and significant myocardial infarction and to predict the successful response to aortocoronary bypass graft surgery.

Blood Pressure↗
PubMed1982

Imaging of platelets in right-sided extracardiac conduits in humans.

As a connection between the systemic venous ventricle and the pulmonary artery, valved Dacron extracardiac conduits have remarkably influenced the surgical approach to many complex congenital heart defects. Obstruction of the conduit, however, can reduce the long-term effectiveness of this corrective procedure. In addition to stenosis of the porcine valve, formation of thick fibrous neointima plays a major role in the pathogenesis of conduit obstruction. The purpose of this study was to determine whether platelet deposition could be demonstrated in these conduits by external imaging with In-111-labeled autologous platelets. After injection of labeled platelets either immediately after operation or on the fifth to eighth postoperative day, imaging was performed by standard procedures. Eight of nine patients had platelet accumulation in the conduit, and treatment with aspirin and dipyridamole caused no recognizable change in platelet deposition. This study demonstrates the feasibility of imaging platelet deposition in Dacron conduits and shows that the pattern of deposition varies with time.

Adolescent↗
PubMed1982

Systemic thromboembolism in mitral and aortic Starr-Edwards prostheses: a 10-19 year follow-up.

Our study comprised 302 consecutive patients seen between 1962 and 1971 who underwent mitral (MVR) (132 patients) or aortic valve replacement (AVR) (170 patients) with a Starr-Edwards prosthesis because of advanced mitral or aortic incompetence. The follow-up interval was 10-19 years. For more recent valve models (1200/1260 aortic or 6120/6310 mitral), the probability of a surviving patient remaining free of systemic thromboembolism after 10 years was 70% for MVR and 74% for AVR. The probability of freedom from thromboembolism was less than this for the earlier valve models; the probability for the entire group at 10 years was 66% and at 15 years was 58%, with no significant difference between AVR and MVR. About one-fourth of the patients with an embolism (20% MVR, 27% AVR) had more than one embolic event. Of all emboli, most (86% MVR, 84% AVR) were cerebral, about half (48% MVR, 57% AVR) left a neurologic deficit, and about one-tenth (11% MVR, 10% AVR) led to death. Of the predictive factors reviewed, the incidence of emboli was significantly higher only in patients with MVR considered to have inadequate anticoagulation (p less than 0.01) and in patients receiving model 6000 mitral prosthesis (p less than 0.02). This long-term follow-up study of patients with a Starr-Edwards prosthesis reveals that systemic embolism is a persistent and significant problem.

Adolescent↗