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R Pifarre

Publications and source records attributed to R Pifarre.

At least 55 records · Page 3Linked to original sources
PubMed1991

Laboratory assays for the evaluation of recombinant hirudin.

Several laboratory methods are available to measure the anticoagulant activity of recombinant hirudin (r-hirudin), a potent thrombin inhibitor. These assays include clot-based, amidolytic, immunologic and physicochemical techniques. Although r-hirudin, like heparin, is an effective anticoagulant, the mechanism of action of the two agents is different. Thus it is not surprising that the global tests, such as the prothrombin time (PT), partial thromboplastin time (APTT) and the Heptest (Haemachem, Inc., St. Louis, Mo., USA), do not show adequate responses to r-hirudin. In the range of 0.5-10.0 microgram/ml, where full anticoagulation is achieved, as determined by animal models of thrombosis, these assays show little to no prolongation of the time to clot. In order to find a more suitable assay system, modifications of the above assays were evaluated. The diluted APTT and diluted Heptest showed linear concentration-dependent responses to lower levels of r-hirudin with an enhanced sensitivity than that of the classical assays. On the other hand, the diluted thrombin time was too sensitive. Whole-blood clotting assays, ACT and thrombelastograph, effectively measured r-hirudin levels up to 25 micrograms/ml. The amidolytic anti-factor IIa assay, specific for evaluating direct thrombin inhibition, was very effective particularly when modified to decrease the sample:thrombin ratio. This assay may be useful in quality control since it is biochemically defined, and reagents are easily standardized. The relevance of the results of the anti-IIa assay to clinical conditions, however, remains to be determined. Thrombin generation assays have limited value in monitoring the anticoagulant effect of r-hirudin since the effect of thrombin inhibition by r-hirudin on coagulation feedback mechanisms, and thus the effect on thrombin generation, appears to be minimal. Immunologic methods such as ELISA and RIA are under development, but they may only be useful for the direct quantitation of absolute levels of r-hirudin and not for monitoring the clinical anticoagulant action. Furthermore, these assays are only sensitive to sub-microgram/ml levels. Therefore, thrombin-based clotting and amidolytic assays may at present be the best choice for evaluating the functional, clinical antithrombotic effects of r-hirudin.

Blood Coagulation↗
PubMed1991

Some objective considerations for the neutralization of the anticoagulant actions of recombinant hirudin.

Recombinant hirudin (r-hirudin) is currently under development as an anticoagulant for use in surgery, therapeutic anticoagulation, disseminated intravascular coagulation and other pathologic states involving the generation of thrombin. Circulating levels of r-hirudin as an antithrombotic agent range from 2 to 20 micrograms/ml (0.1-1.0 mg/kg) as determined in an animal model of stasis thrombosis. In order to establish a relationship between the r-hirudin circulating level and bleeding, we utilized a rabbit ear blood loss model. r-Hirudin did not produce any loss of blood at dosages up to 20 micrograms/ml i.v. (1.0 mg/kg). When the circulating levels were maintained at 20 micrograms/ml for periods of up to 3 h, no increase in blood loss was observed. At 50 and 100 micrograms/ml initial circulating levels (2.5 and 5.0 mg/kg) a dose-dependent increase in the blood loss was observed which was equivalent to that observed with 1.25 and 2.5 mg/kg i.v. heparin. Such levels of r-hirudin are not expected in clinical usage. In contrast to heparin, the anticoagulant actions of r-hirudin were not neutralized by protamine sulfate, platelet factor 4, other polycationic agents and heparinase. In our studies, the blood loss induced by greater than 2.0 mg/kg i.v. dosages of r-hirudin in an animal model was neutralized by the administration of an activated prothrombin complex concentrate at 25 U/kg. In a similar experimental setting, r-factor VIIa was also partially effective. These studies suggest that r-hirudin anticoagulation may not require neutralization, since bleeding effects are not observed at effective antithrombotic dosages in individuals with normal hemostatic status.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3 in cardiac-transplant recipients.

BACKGROUND: A sudden increase in the incidence of post-transplantation lymphoproliferative disorder among the patients in our cardiac-transplantation program was temporally related to introduction of the immunosuppressive drug OKT3. This monoclonal antibody has come to be widely used in recent years both to prevent and to treat rejection after cardiac transplantation. METHODS: In order to identify variables that predict the development of post-transplantation lymphoproliferative disorder, we analyzed retrospectively a series of 154 consecutive cardiac-transplant recipients at a single institution. Univariate analyses and multivariate analysis by logistic regression were performed. RESULTS: Among 75 patients who did not receive OKT3, post-transplantation lymphoproliferative disorder developed in 1 (1.3 percent), as compared with 9 of 79 patients who received the drug (11.4 percent); the incidence among the OKT3-treated patients was ninefold higher (odds ratio, 9.5; 95 percent confidence interval, 1.6 to 54.7). According to multivariate analysis, the only factor significantly associated with the development of post-transplantation lymphoproliferative disorder was the use of OKT3 (P = 0.001). A significant increase in risk with increasing doses was also apparent: 4 of 65 patients who received a cumulative dose of 75 mg of OKT3 or less (6.2 percent) had post-transplantation lymphoproliferative disorder, whereas 5 of 14 patients who received more than 75 mg had the disorder (35.7 percent; P less than 0.001). CONCLUSION: The addition of OKT3 to the immunosuppressive regimen increases the incidence of post-transplantation lymphoproliferative disorder after cardiac transplantation, and the risk increases sharply after cumulative doses greater than 75 mg. We suggest that the risks and benefits of prophylactic OKT3 administration be reassessed in the light of these findings, particularly since the value of prophylactic immunotherapy in cardiac-transplant recipients remains to be clearly established.

Antibodies, Monoclonal↗
PubMed1990

Internal mammary artery revascularization in the patient on long-term renal dialysis.

Twenty-six patients on long-term renal dialysis underwent coronary artery bypass grafting. The patients were divided into two groups: group 1, (16 patients) saphenous vein bypass grafts, and group 2, (10 patients) internal mammary artery in combination with saphenous vein bypass grafts. Both groups were similar in terms of cardiac hemodynamics and previous number of myocardial infarctions, though more group 1 patients were in New York Heart Association class III or IV. Patients in group 1 received 2.9 bypass grafts per patient; patients in group 2 received 4.0 bypass grafts per patient (4 with bilateral mammary arteries). No wound healing problems occurred in either group. Blood replacement was similar for both groups (group 1, 5.5 units/patient; group 2, 5.3 units/patient). More platelets were given to group 1 patients (16.2 units/patient) than group 2 patients (3.1 units/patient). We conclude that use of the internal mammary artery in patients on long-term renal dialysis does not alter wound healing or increase blood loss in this subset of patients.

Blood Transfusion↗
PubMed1990

Progression of native coronary artery disease at 10 years: insights from a randomized study of medical versus surgical therapy for angina.

Repeat coronary angiography was performed in 42 patients 10 years after randomization to medical (n = 21) or surgical (n = 21) therapy for chronic angina. The native coronary arteries were classified into 15 angiographic segments and 3 arterial trunks for analysis of progression of coronary artery disease. The incidence rate of disease progression in coronary segments was 24% and 28% in medically and surgically treated patients, respectively (p = NS). Grafted segments showed a 38% rate of disease progression, which was higher than the 18% rate of for nongrafted segments (p less than 0.001) and the overall rate of 24% for medically treated patients (p less than 0.01). Similarly, 29 (94%) of 31 grafted arteries exhibited disease progression compared with 19 (59%) of 32 nongrafted arteries (p less than 0.01) and 42 (67%) of 63 arteries in medically treated patients (p less than 0.01). In grafted vessels, disease progression occurred more often in arteries proximal (84%) to the anastomosis than in arteries distal (16%) to graft insertion (p less than 0.001). Progression occurred in 46% of proximal segments compared with 23% of distal segments (p less than 0.02). Progression was seen in 23 (55%) of 43 segments with an occluded graft compared with 30 (31%) of 96 segments with a patent graft (p less than 0.02). Ten years after randomization, medically and surgically treated patients showed a comparable rate of disease progression in coronary segments. However, surgical therapy appeared to significantly accelerate atherosclerotic progression in the grafted vessels, especially in the proximal portions. Occluded grafts also correlated with an adverse effect on disease progression.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1990

Myocardial revascularization for the third time. Clinical characteristics and follow-up.

Twenty-five patients presenting for a third revascularization procedure were retrospectively reviewed at Loyola University Medical Center, Maywood, IL. This represents 0.5 percent of the total revascularization cases over a five-year period extending from 1985 through 1989. Perioperative mortality was none, and seven complications occurred in six patients. Internal mammary arteries were used for revascularization in 60 percent of this group. Follow-up reveals that only one patient has died secondary to an arrhythmia. All patients except one are symptomatically improved, and 18 patients remain angina free at a mean follow-up of 22.3 months. It is therefore concluded that patients are clinically improved with a third revascularization, and this procedure should be offered as an effective means of treatment.

Female↗
PubMed1990

The use of the Jarvik-7 total artificial heart and the Symbion ventricular assist device as a bridge to transplantation.

The proliferation of transplantation programs has not been paralleled by a similar increase in the availability of organ donors. Between 1984 and 1987, 104 orthotopic heart transplantations were performed at Loyola University Medical Center. During the same period, 25 patients died while awaiting a donor organ. To reduce the mortality, we began using the total artificial heart (TAH) and a ventricular assist device (VAD) as a bridge to transplantation in 1988. Of 29 patients who underwent transplantation, 15 patients required a TAH and three patients required a VAD as a bridge. The underlying heart conditions were ischemic cardiomyopathy (11 patients), dilated cardiomyopathy (5 patients), giant cell myocarditis (1 patient), and allograft failure (1 patient). The average duration of mechanical support was 10 days (range, 1 to 35 days). Of the 17 patients who successfully underwent transplantation, 1 patient died at 17 days because of acute rejection of the transplanted heart, and another patient died at 14 days because of a cerebral vascular event. Fifteen patients (83%) were long-term survivors. Nine patients required reoperation for bleeding. While the mechanical device was in place, the activated clotting time was maintained between 170 and 200 seconds with heparin. Dipyridamole was given. We conclude that the TAH and VAD are excellent mechanical bridges to transplantation.

Adolescent↗
PubMed1989

Median sternotomy for implantable cardioverter/defibrillator.

The automatic implantable cardioverter/defibrillator is an accepted mode of therapy for medically refractory sustained ventricular tachycardia or fibrillation. At the Loyola University Medical Center, Maywood, Ill, 39 implantations were performed in a 14-month period. The method of implantation was the median sternotomy. Our population included 9 patients in whom sternotomies had to be redone and 17 patients with concomitant revascularization. Two patients died due to pump failure, and one major complication (infection) occurred that was directly related to the automatic implantable cardioverter/defibrillator. The median sternotomy, because of good results, continues to be our method of choice for insertion of the automatic implantable cardioverter/defibrillator.

Electric Countershock↗
PubMed1989

Cardiac transplantation: a prospective comparison of ketamine and sufentanil for anesthetic induction.

The hemodynamic effects of ketamine, 1.5 mg/kg, or sufentanil, 3.4 +/- 0.3 micrograms/kg, were studied prospectively for the anesthetic induction of 20 patients with cardiomyopathies undergoing cardiac transplantation. Plasma epinephrine (EPI), norepinephrine (NE), and sufentanil levels were also obtained. Measurements were taken at various times before induction and following intubation. Following ketamine, progressive increases (P less than 0.05) in mean arterial pressure (28%, MAP), mean pulmonary artery pressure (56%, PAP), central venous pressure (109%, CVP), and pulmonary capillary wedge pressure (84%, PCWP) occurred over time, whereas the cardiac index (CI), stroke volume index (SVI), and stroke work index (SWI) remained unchanged or decreased. The use of sufentanil was associated with no significant changes in MAP, PAP, CVP, PCWP, CI, SVI, or SWI. The heart rate (HR) did not significantly change in either group. Plasma NE significantly increased (31%) in the ketamine group, peaking at 10 minutes; whereas EPI levels did not significantly change in either group. Plasma sufentanil did not reflect the microgram/kg or microgram/BSA administered dose, suggesting individualized distribution kinetics. Since perioperative morbidity and mortality did not differ between groups, both ketamine and sufentanil are acceptable drugs for the anesthetic induction for cardiac transplantation. However, the dissimilar hemodynamic effects caused by ketamine and sufentanil suggest that this conclusion may not be applicable to the patient with a cardiomyopathy undergoing noncardiac surgery.

Adolescent↗
PubMed1989

Catecholamine sensitive right ventricular outflow tract tachycardia: intraoperative mapping and ablation of a free-wall focus.

A patient with catecholamine-sensitive right ventricular outflow tract tachycardia refractory to pharmacological therapy underwent intraoperative mapping and cryoablation. Epicardial and endocardial mapping demonstrated earliest ventricular activation in the free-wall of the outflow tract, and cryoablation of the area resulted in surgical cure. No histologic abnormalities at the site of tachycardia origin were detected. Catecholamine sensitivity does not appear to result from a diffuse myocardial process, and permanent ablation of the tachycardia in this group of patients with a regional procedure is feasible.

Catecholamines↗
PubMed1989

Coronary revascularization and implantation of the automatic cardioverter/defibrillator: reliability of immediate intraoperative testing.

Concomitant coronary revascularization and implantation of the automatic cardioverter/defibrillator is an increasingly common procedure. To determine whether cardioversion/defibrillation thresholds measured after weaning patients from cardiopulmonary bypass are sufficient to justify immediate implantation of the pulse generator, we prospectively compared postpump values to those obtained 1 week later in five patients. R-wave amplitudes during both sinus rhythm and ventricular tachycardia, lead impedance, defibrillation thresholds and cardioversion thresholds remained stable or improved from the postpump to the 1 week values. Five other patients had the generator implanted at the time of revascularization. Immediate postbypass cardioversion thresholds (mean 10 +/- 8 joules) in these ten patients did not significantly differ from those of 20 nonpump implantations (VT mean 7 +/- joules; VF 15 +/- 4 joules and defibrillation thresholds mean 17 +/- 6 joules). These findings suggest that the residual effects of cardioplegia, core-cooling and operative ischemia have no significant effects on intraoperative testing of implanted defibrillators. This clinical experience supports the practice of immediate implantation of the pulse generator at the time of revascularization.

Cardiopulmonary Bypass↗
PubMed1989

Cardiac surgery for chronic renal dialysis patients.

Twenty-two open-heart operations have been performed on 21 patients receiving chronic renal dialysis. These cases include 16 aortocoronary bypasses and six valve replacements. The average time on dialysis prior to surgery was 26 months; 18 of 21 patients were in NYHA grade 3 or 4. Twenty-seven postoperative complications occurred, with six requiring further surgery and 21 treated nonsurgically. Two perioperative deaths occurred, both due to sepsis. Long-term follow-up was achieved on all hospital survivors. Ten patients remain alive with a mean follow-up of 21 months. At a mean of 16.5 months after surgery, nine deaths occurred, with only two due to known cardiac problems. In summary, indicated cardiac surgery can be performed on chronic renal dialysis patients with a reasonable morbidity and mortality; however, the long-term survival of our patients has not been assured by a successful cardiac operation.

Adult↗
PubMed1989

Cardiac transplantation.

Cardiac transplantation is now an accepted therapeutic procedure in the management of patients suffering from end-stage congestive heart failure. The advances in myocardial preservation, long-distance procurement, immunosuppression, improvement in the treatment of infectious diseases, and utilization of endomyocardial biopsy in the diagnosis of rejection have made its application widespread and resulted in improved survival.

Graft Rejection↗
PubMed1989

Placement of intra-aortic balloon pump allows definitive biliary surgery in patients with severe cardiac disease.

This study reviews the cases of 15 patients with severe cardiac disease treated with the intra-aortic balloon pump (IABP) to improve cardiac status so that they could undergo definitive cholecystectomy. The 14 men and one woman ranged in age from 49 to 74 years. Indications for cholecystectomy included acute cholecystitis in nine patients and chronic cholecystitis in six patients. All patients had prior myocardial infarction, and in two patients this had occurred within 2 months of operation. All patients were Goldman's Class IV. Eight had severe cardiomyopathy. Mean ventricular ejection fraction was 21% +/- 3%. Cardiac index was 2.2 +/- 0.2 L/m/m2, and pulmonary artery pressure (PAP) was 51 +/- 5/23 +/- 2 mm Hg. After IABP placement, pulmonary wedge pressure decreased in all patients, from 24 +/- 3 mm Hg to 16 +/- 2 mm Hg (p less than 0.01). PAP systolic pressure decreased to 38 +/- 3 mm Hg (p less than 0.01), and PAP diastolic pressure decreased to 18 +/- 2 mm Hg (p less than 0.05). All patients had cholecystectomy. Five patients had intraoperative cholangiography. One of these five patients had a common bile duct exploration, and another underwent cystgastrostomy. Two patients died postoperatively of arrhythmias. Thirteen patients are alive 3 months to 7 years after operation, without biliary symptoms. Three patients have had orthotopic heart transplants. We conclude that IABP significantly improves cardiac performance so that many patients who have severe cardiac disease can undergo definitive biliary surgery.

Aged↗