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Biomedical subjects

J C Alexander

Publications and source records attributed to J C Alexander.

At least 19 recordsLinked to original sources
PubMed2000

Oral glycoprotein IIb/IIIa inhibition with orbofiban in patients with unstable coronary syndromes (OPUS-TIMI 16) trial.

BACKGROUND: Although intravenous glycoprotein IIb/IIIa inhibitors are beneficial in patients with acute coronary syndromes, prolonged oral IIb/IIIa inhibition might provide an additional reduction in recurrent events. METHODS AND RESULTS: Investigators at 888 hospitals in 29 countries enrolled 10 288 patients with acute coronary syndromes, which was defined as ischemic pain at rest within 72 hours of randomization, associated with positive cardiac markers, electrocardiographic changes, or prior cardiovascular disease. Patients received aspirin and were randomized to receive, for the duration of the trial, (1) 50 mg of orbofiban twice daily (50/50 group), (2) 50 mg of orbofiban twice daily for 30 days followed by 30 mg of orbofiban twice daily (50/30 group), or (3) a placebo. The primary composite end point was death, myocardial infarction, recurrent ischemia requiring rehospitalization, urgent revascularization, or stroke. The trial was terminated prematurely because of an unexpected increase in 30-day mortality in the 50/30 orbofiban group. Mortality through 10 months was 3.7% for the placebo group versus 5.1% in the 50/30 group (P=0.008) and 4.5% in the 50/50 group (P=0.11). There were no differences in the primary end point (22.9%, 23.1%, and 22.8%, for the placebo, 50/30, and 50/50 groups, respectively). Major or severe bleeding (but not intracranial hemorrhage) was higher with orbofiban; it occurred in 2. 0%, 3.7% (P=0.0004), and 4.5% (P<0.0001) of patients, respectively. Exploratory subgroup analyses found that patients who underwent percutaneous coronary intervention had a lower mortality and a significant reduction in the composite end point (P=0.001) with orbofiban. CONCLUSIONS: -Fixed-dose orbofiban failed to reduce major cardiovascular events and was associated with increased mortality in this broad population of patients with acute coronary syndromes; however, a benefit was observed among patients who underwent percutaneous coronary intervention.

Administration, Oral↗
PubMed1998

Method for creation of the aortotomy site for saphenous vein grafts.

Saphenous vein coronary artery bypass grafting requires a proximal anastomosis of the vein to the aorta. A variety of techniques have been described to create the aortotomy. We have developed a four-sided knife (Xcision Scalpel; patent pending, Research Medical, Inc, Midvale, UT) that facilitates the creation of a more uniform circular aortotomy. The purpose of this communication is to describe the knife and the technique for its use.

Aorta↗
PubMed1998

False aneurysm of the right internal mammary artery. Late rupture after sternotomy.

This report describes a late, near-fatal rupture of a false aneurysm of the right internal mammary artery subsequent to coronary artery bypass grafting. The patient presented to us in shock due to hemorrhaging, 8 weeks after bypass surgery that had been complicated by sternal fracture, dehiscence, and infection. Emergent thoracotomy and suture ligation controlled the hemorrhage. To the best of our knowledge, this is the 1st reported case of late massive hemorrhage caused by injury to an internal mammary artery after sternotomy. The literature is reviewed and discussed.

Aged↗
PubMed1996

Hemodynamic stabilization of acute prosthetic valve thrombosis using percutaneous catheter manipulation.

Thrombosis of a tilting-disk prosthetic heart valve can be an acute and potentially life-threatening problem. Surgical thrombectomy, valve replacement, or systemic thrombolytic agents have been successfully employed in the management of such cases. Some patients, however, may not survive the acute episode long enough to receive definitive surgical therapy. For such patients, temporary hemodynamic stabilization might be achieved by re-establishing partial valve disk mobility. This report describes a technique for re-establishing valve disk mobility in an acutely compromised patient by using a percutaneously introduced "rigid" catheter to manipulate an entrapped tilting-disk valve in the aortic position.

Aged↗
PubMed1995

Modulation of alloreactivity in transplant recipients by phenotypic manipulation of donor endothelium.

Phenotypic manipulation of allograft endothelium to reduce immunogenicity would have a significant impact on transplantation. In this study we have demonstrated that random seeding of a heart allograft with endothelium, of host origin, not only promotes long-term survival, but reduces the requirement for pharmacologic immunosuppression. We propose that this simple technology could easily be extrapolated to the clinical arena where hypothermia and preservation solutions have allowed allografts to remain ex vivo for extended periods.

Animals↗
PubMed1995

Cardiopulmonary bypass with adequate flow and perfusion pressures prevents endotoxaemia and pathologic cytokine production.

Endotoxin and cytokine inflammatory mediators comprise the afferent and efferent limbs of the 'acute phase response'. During cardiopulmonary bypass (CPB) there may be gut translocation of endotoxin and contact activation of lymphocytes. It has been hypothesized that the haemodynamic instability encountered following CPB is caused by the 'acute phase response'. In this study we attempted to quantify the acute phase response in patients undergoing open-heart surgery and determine the influence of these cytokines on perioperative morbidity. Four perioperative blood samples were drawn from 20 consecutive patients undergoing coronary artery bypass grafting (CABG). These samples were assayed for endotoxin and four cytokines. In all cases the cardiac index was maintained > 2.4 l/min/m2 during nonpulsatile normothermic bypass (37 degrees C) and > 1.8 l/min/m2 during nonpulsatile hypothermic bypass (28 degrees C), and the perfusion pressure > 60 mmHg. Endotoxin was not detected in any of the test samples despite positive nonpatient controls. Interleukin 6 (IL-6) and tumour necrosis factor (TNF) were not detected despite an assay sensitivity of 80 and 10 pg/ml, respectively. TNF was detectable with an assay sensitivity of 0.5 pg/ml although there were no significant differences within the group. Interleukin 1 (IL-1) was detected (range = 0.98 - 9.09 ng/ml) in patients and again there were no trends within the group. The platelet activating factor (PAF) values peaked at crossclamp release (1.3 ng/ml versus a baseline of 0.2 ng/ml); however, there was no significant difference within the study.

Analysis of Variance↗
PubMed1995

The haemostatic effectiveness of autologous platelet rich plasma sequestered after heparin administration and institution of cardiopulmonary bypass.

Preoperative harvesting and postoperative reinfusion of autologous platelet rich plasma (PRP) has been reported to decrease blood loss as well as the requirement for homologous blood transfusion following cardiopulmonary bypass (CPB). We have developed a technique of intraoperative PRP sequestration which occurs during the initial period of CPB after the patient's circulation is supported and heparin has been given (PRP+). This process does not require any additional hardware, personnel or expense and it is performed without difficulty or complication. To evaluate the effect of PRP+ sequestration and reinfusion on blood loss and homologous blood requirement after CPB, we randomly assigned 126 consecutive patients undergoing elective open heart surgery into the experimental group 1 (PRP+) (n = 64) or the control (no platelet pheresis) group 2 (n = 52). A third group (n = 10) were not included in the randomization. Patients in group 3 had PRP prepared by conventional techniques (PRPc) prior to heparin administration and given to the patient after protamine infusion. Aggregation and activation studies were performed on the PRP+, PRPc, and blood bank platelets (BBP). Per cent aggregation of PRP in response to ADP was superior to that of BBP. There were no significant differences in ADP induced aggregation between PRP+ and PEPc. There was no significant difference in platelet activation (CD62) or number between the three groups. Patients infused with PRP+ showed significantly increased aggregation to ADP when compared with untreated patients 120 minutes after return to the ICW. Furthermore, more homologous haemostatic components (platelets/fresh frozen plasma) were required in the control group. We have demonstrated that collection of autologous PRP+ after administration of heparin does not interfere with its haemostatic effectiveness compared with PRPc prepared before the initiation of bypass. Moreover, this can be performed universally in haemodynamically unstable patients without any additional costs.

Aged↗
PubMed1995

The relationship between hospital charges and a modified Parsonnet risk score.

Health care now consumes approximately 14 percent of the U.S. Gross National Product (GNP). The amount of money spent on health care in America per capita and as a percentage of GNP far exceeds that of any other industrialized country. Currently, the financial burden of health care is being shouldered by government and business. The expenditure of billions of dollars of corporate profits on health care progressively undermines the global competitiveness of American business. These economic realities have emerged as the dominant driving force in health care reform. Cost control efforts to date have focused on strategies to limit inpatient hospital expenditures. The DRG prospective payment system is designed to reimburse a fixed sum based on the diagnostic category of the patient. The DRG payment is essentially independent of underlying patient characteristics that can potentially drive up expenditures. The work reported in this article was done to develop a descriptive formula that could be used to predict resource consumption in the care of patients. The financial viability of a hospital depends on its ability to predict expenditures, allocate resources, and choose its service areas correctly. Errors in financial forecasting in the era of prospective payment will result in financial failures of entire institutions.

Age Factors↗
PubMed1993

Intraoperative procurement of autologous fibrin glue.

A method of intraoperative procurement of autologous fibrin glue is described. The relative efficacy of our autologous preparation is compared with that of fibrin glue made with homologous cryoprecipitate. Experimentally, the fibrinogen content and the strength are less than those found in cryoprecipitate and appear related to the fibrinogen content of the autologous plasma used as substrate in the fibrin glue reaction. Clinically, no significant differences are noted in the performance of autologous fibrin glue. We believe the absence of the risk of blood-borne infection with the autologous product is a major advantage.

Adhesiveness↗
PubMed1991

On the dynamics of bursting systems.

The dynamics of three-variable models of bursting are studied. It is shown that under certain conditions, the dynamics on the attractor can be essentially reduced to two dimensions. The salient dynamics on the attractor can thus be completely described by the return map of a section which is a logistic interval map. Two specific bursting models from the literature are shown to fit in the general framework which is developed. Bifurcation of the full system for one case in investigated and the dynamical behavior on the attractor is shown to depend on the position of a certain nullcline.

Animals↗
PubMed1988

Decreased platelet number and function and increased fibrinolysis contribute to postoperative bleeding in cardiopulmonary bypass patients.

We simultaneously evaluated platelet and fibrinolytic parameters to assess their individual and combined contributions to postoperative blood loss in cardiopulmonary (CP) bypass patients. Platelet count, platelet aggregability, hematocrit, plasminogen (PLG) concentration, alpha 2-antiplasmin (AP) concentration, free protease activity (fPA), and antithrombin-III (AT-III) were measured in nine patients undergoing surgery using cardiopulmonary bypass. Chest tube drainage was used as the measure of postoperative blood loss. Hematocrit, platelet count, PLG, AP, and AT-III all decreased during CP bypass, with PLG and AT-III decreasing much more than dilution. During CP bypass, platelet aggregability to ADP did not change significantly from pre-bypass, but aggregability to arachidonic acid (AA) decreased significantly. Following protamine administration there was a large increase (83%) in fPA, the platelet count showed a further drop (from 61% to 50% of pre-bypass levels), and platelet aggregability decreased significantly (from 95% to 34% of pre-bypass levels for ADP, and from 55% to 11.9% for AA). Chest tube drainage during the first four postoperative hours correlated positively (p less than 0.05) with the combination of increase in free protease activity and decrease in platelet count. The total chest tube drainage correlated significantly with the combination of decrease in platelet count and the decrease in platelet aggregability. These combinations of changes correlated significantly with postoperative blood loss whereas the individual changes did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗
PubMed1987

Calcium-accentuated ischemic damage during reperfusion: the time course of the reperfusion injury in the isolated working rat heart model.

The purpose of this study was to determine the time course of calcium-induced postischemic reperfusion injury to the myocardium, using an initial short-term calcium-enriched reperfusion solution. The isolated rat heart model was subjected to 30 min of normothermic potassium cardioplegia-induced ischemic arrest. Control hearts received normal calcium Krebs-Henseliet buffer (KHB) reperfusion. Experimental hearts were challenged with 10 min of calcium-enriched (KHB) reperfusion starting at 0, 1, 2, 5, 15, and 30 min after the beginning of reperfusion. Aortic flow recovery 60 min after reperfusion was used to determine functional recovery. Control hearts recovered 82 +/- 3% of preischemic aortic flow. Hearts which received calcium challenge at 0 and 1 min after the start of reperfusion recovered 43 +/- 4 and 69 +/- 3% of preischemic aortic flow, respectively (P less than 0.01 and P less than 0.05, respectively). Hearts which received calcium challenge 2, 5, 15, and 30 min after reperfusion recovered 75 +/- 2, 80 +/- 2, 85 +/- 2, and 83 +/- 2% of preischemic aortic flow, respectively. Our results indicate that the postischemic myocardium is very susceptible to calcium-accentuated ischemic damage during the initial period of reperfusion. The postischemic heart, however, quickly recovers its ability to withstand a calcium challenge. Five minutes after the start of reperfusion the heart is not influenced by calcium challenge.

Animals↗
PubMed1987

Biological observations from feeding heated corn oil and heated peanut oil to rats.

Five groups of male weanling rats were provided purified diets containing 15% by weight of either fresh or laboratory-heated corn oil (FCO, HCO) or fresh, laboratory-heated, or commercial pressure deep-fry peanut oil (FPO, HPO, PPO). Total weight gain, feed consumption, and feed efficiency were consistently greater for the FCO, FPO, and PPO groups. Although relative heart weights were unaffected, the HCO and HPO produced elevated liver and kidney weights. The dietary fats had no effect on the hematological status of the animals or the proportions of cells comprising the total leukocytes of the blood. Physical, chemical, and microscopic evaluation of the urine detected no pathologic conditions. Rats fed diets containing HCO or HPO demonstrated toxicity of thermally oxidized fats by the appearance of diarrhea, dermatitis, seborrhea, and hair loss. Histological examinations revealed injury of the thymus by all fat samples except the FCO; the liver was damaged by the HCO, HPO, and PPO, and the testes and epididymides by HPO and PPO. In the latter case there was complete cessation of spermatogenesis.

Animals↗
PubMed1986

Spontaneous oscillations in two 2-component cells coupled by diffusion.

Mathematical examples are presented of oscillators with two variables which do not oscillate in isolation, but which do oscillate stably when coupled with a twin via diffusion. Two examples are presented, the Lefever-Prigogine Brusselator and a system used to model glycolytic oscillations. The mathematical method is not the usual bifurcation theory, but rather a type of singular perturbation theory combined with bifurcation theory. For both examples, it is shown that all stationary solutions are unstable for appropriate parameter settings. In the case of the Brusselator, it is further shown that there exist limit cycles; i.e. stable oscillations, in this parameter range. A numerical example is presented.

Cell Physiological Phenomena↗