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Biomedical subjects

R W Olson

Publications and source records attributed to R W Olson.

At least 19 recordsLinked to original sources
PubMed1993

Beneficial effects of combined thromboxane synthase inhibition/receptor blockade with CGS 22652 in a canine model of coronary thrombosis.

Various antiplatelet agents were examined for their effectiveness as adjuncts to thrombolytic therapy in a canine model of thrombin-induced coronary thrombosis. Aspirin (5 mg/kg i.v. bolus), CGS 15435A (thromboxane synthase inhibitor (TxSI), 0.1 mg/kg i.v. bolus +0.04 mg/kg per h) and BM 13.505 (thromboxane receptor antagonist (TxRA), 0.5 mg/kg i.v. bolus +0.2 mg/kg per h) administered concurrently with streptokinase (750,000 units/h) were examined for their effects on reperfusion and reocclusion, as were a combination therapy with CGS 15435A + BM 13.505 or the dual TxRA/TxSI inhibitor, CGS 22652 (1 mg/kg i.v. bolus +0.4 mg/kg per h). All dogs received heparin (150 U/kg bolus + 50 U/kg per h) throughout the experimental protocol. Survival analysis at reperfusion indicated that thrombolysis was significantly improved in dogs treated with CGS 15435A, BM 13.505, CGS 15435A+BM 13.505 or CGS 22652 over that of vehicle-treated animals. Both dual inhibitor groups and the BM 13.505 group were significantly different from aspirin. Aspirin-treated dogs were not different from vehicle. Otherwise, all treatments differed from the vehicle-treated group at reocclusion. Time and incidence of reocclusion for CGS 22652 was significantly improved over that of BM 13.505. Residual thrombus weight was significantly reduced in the CGS 22652-treated and BM 13.505 + CGS 15435A-treated animals. These findings demonstrate that streptokinase-induced thrombolysis is accompanied by TxA2/prostaglandin H2 synthesis and platelet activation and suggest a role for platelet activation during reocclusion following clot lysis. These studies also show it is possible to combine the beneficial effects of both a TxRA and TxSI into a single chemical entity, CGS 22652, which, when administered as adjunctive therapy to streptokinase, results in an apparent synergistic antithrombotic effect.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Comparison of hirudin and heparin as adjuncts to streptokinase thrombolysis in a canine model of coronary thrombosis.

Recombinant desulfatohirudin (HI), a potent and specific thrombin inhibitor, was compared with heparin (HE) as an adjunct to streptokinase thrombolysis. In pentobarbital-anesthetized dogs, an occlusive thrombus (whole blood+thrombin) was introduced into the left anterior descending coronary artery (LAD) with superimposed endothelial damage and distal high-grade stenosis. Intravenous infusion of saline (vehicle), HI (0.3 mg/kg followed by 0.3 mg/kg per hour, 1 mg/kg followed by 1 mg/kg per hour, or 2 mg/kg followed by 2 mg/kg per hour), or HE (60 units/kg followed by 40 units/kg per hour or 100 units/kg followed by 60 units/kg per hour) was initiated 15 minutes before streptokinase (750,000 units for 60 minutes) administration. Vessel patency was monitored for 180 minutes after streptokinase administration with a volume flow probe on the proximal LAD. In dogs treated with no adjunctive agent (saline control), none of the vessels were recanalized with streptokinase. Both HI and HE promoted reperfusion, inhibited reocclusion, and reduced the residual thrombus mass in a dose-dependent fashion. However, at comparable levels of therapeutic anticoagulation (activated partial thromboplastin time [APTT] = 1.5-2.0 times baseline) HI exhibited a higher incidence of reperfusion (eight of eight dogs [100%] versus one of eight dogs [12%]), a shorter time to reperfusion (33 +/- 6 versus 59 minutes), a longer duration of initial reperfusion (106 +/- 21 versus 10 minutes), and a smaller residual thrombus mass than did HE. Likewise, the slope of the relation between the APTT prolongation and the total reperfusion time ("anticoagulation/antithrombosis profile") was almost five times higher for the combined HI data than for the HE data. Our results indicate that HI is more effective than HE in enhancing and sustaining coronary recanalization with streptokinase at a HI dose that modestly prolongs coagulation time and does not alter bleeding times.

Animals↗
PubMed1989

Phosphatidylglycerol, lecithin/sphingomyelin ratio and respiratory distress syndrome in diabetic and non-diabetic pregnancies.

Samples of amniotic fluid from 514 non-diabetic and 69 diabetic patients were analyzed for phospholipid content. Results were correlated with incidence of respiratory distress syndrome (RDS) in the neonate. The incidence of RDS was 4.5% among diabetics and 5.3% among non-diabetics. In the presence of phosphatidylglycerol (PG), no infant developed RDS while in the absence of PG the incidence of RDS was 16.7% and 14.4%, respectively. In the presence of a mature lecithin/sphingomyelin (L/S) ratio the respective incidence of RDS was 1.6 and 1.8, while with an immature L/S ratio the incidence of RDS was 28.6% and 29%. The incidence of RDS after 37 weeks gestation was 0% among diabetics and 0.6% among non-diabetics. We conclude that amniotic fluid phospholipids are equally predictive of risk for RDS in diabetics as among non-diabetic patients. We suggest that in patients with accurate gestational dating, amniotic fluid analysis for phospholipids might not be necessary to establish fetal lung maturity.

Amniotic Fluid↗
PubMed1987

CGS 15435A, a thromboxane synthetase inhibitor with an extended duration of action: a comparison with dazoxiben.

CGS 15435A, a novel thromboxane (Tx) synthetase inhibitor (5-chloro-1-methyl-2-(3-pyridyl)-3-indolhexanoic acid HCl), had a selectivity for Tx synthetase 100,000-fold greater than that for cyclooxygenase, PGI2 synthetase and lipoxygenase enzymes. In conscious beagles, 1 h following a single 3 mg/kg p.o. dose, serum TxB2 was inhibited 95% by CGS 15435 and 82% by dazoxiben (DAZ). Unlike the short acting Tx synthetase inhibitor DAZ, CGS 15435A significantly inhibited TxB2 formation 4, 6, 12 and 24 h after dosing. Serum levels of 6-keto PGF1 alpha and PGE2 were significantly increased following the administration of either drug. CGS 15435A and DAZ were further examined in a model with known Tx involvement. Thrombotic sudden death, produced in anesthetized rabbits by injection of 0.75 mg/kg arachidonic acid (AA) i.v. resulted in a 45% fall in the platelet count and 0% survival. Pretreatment with DAZ (8.6 mumol/kg i.v.) at 0.25 or 2 h pre-AA resulted in 3 and 42% thrombocytopenia and 100 and 0% survival respectively. CGS 15435A (8.6 mumol/kg i.v.) prevented the increases in plasma TxB2 levels, thrombocytopenia and sudden death with pretreatment at 0.25 h (0% thrombocytopenia and 100% survival) or 24 h (11% thrombocytopenia and 83% survival) before AA. These data indicate that CGS 15435A is a potent and selective Tx synthetase inhibitor with a long duration of action, and suggest that the compound could be useful in chronic, non-symptomatic indications of Tx involvement.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Effects of metoprolol, alone and in combination with lidocaine, on ventricular fibrillation threshold: comparison with atenolol, propranolol, and pindolol.

Metoprolol and other beta-adrenergic blocking drugs are known to exert cardioprotective effects that include significant reduction in occurrence of ventricular fibrillation (VF) following myocardial ischemia and infarction. To help determine the mechanism of these cardioprotective effects, this study evaluated the effect of equipotent beta-blocking doses of metoprolol and three other beta-blockers with differing ancillary properties on ventricular fibrillation threshold (VFT) in the normal canine heart. Metoprolol tartrate (1.0 mg/kg i.v.), atenolol (0.3 mg/kg i.v.), propranolol hydrochloride (0.3 mg/kg i.v.), pindolol (0.03 mg/kg i.v.), or saline control (0.9% NaCl solution; vehicle) was given, alone and in combination with lidocaine (L), to groups of six pentobarbital (32.5 mg/kg i.v.) anesthetized mongrel dogs after control VFT and control isoproterenol-induced (ISO) positive chronotropic effects had been determined. The D- (membrane stabilizing, non-beta blocking) and L- (beta blocking) isomers of propranolol also were administered to separate groups of six anesthetized dogs in a dose of 0.3 mg/kg i.v. Blood samples (venous) were taken before drug or vehicle administration, 10 min after drug/vehicle administration and at half-hour intervals thereafter during experimentation. ISO responses and VFT were determined 5 and 15 min, respectively, after drug/vehicle administration and at half-hour intervals for a total experimental period of 165 min. VF was induced with a train of pulses (5 s, 100 Hz, 3-ms duration, 250-omega resistance) applied by bipolar platinum electrodes to a paced heart (200 beats/min). Voltage (V) was increased every 60 sec (0.25-V increments between 0-3.5 V and 0.5-V increments greater than 3.5 V) until VF occurred. Metoprolol increased VFT significantly (p less than 0.05) and maximally (max delta V = 2.3 +/- 0.7 V) at 135 min postdrug when the ISO-induced increase in heart rate was inhibited (%I ISO) by less than 53%. Max delta V was not significantly increased following i.v. administration of atenolol (0.8 +/- 0.6 V), pindolol (0.1 +/- 0.1 V), or saline (0.1 +/- 0.1 V). Max delta V was 0.5 +/- 0.2 in the D-propranolol-treated group and 0.5 +/- 0.3 in the L-propranolol-treated group. These values did not differ from max delta V obtained in the propranolol-treated group (0.6 +/- 0.4 V). Changes in VFT for all groups were, over time, negatively correlated with %I ISO and were not dependent on membrane stabilizing effect (metoprolol, propranolol (D,DL), pindolol), intrinsic sympathomimetic activity (pindolol), or cardioselectivity (metoprolol, atenolol).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Management of the fetus with urinary tract dilatation.

This report describes our experience with 18 pregnant women who presented to our center with suspected fetal urinary tract dilatation. The patients were divided into 4 groups: group I had unilateral fetal urinary tract dilatation and normal amniotic fluid volume, group II had bilateral dilatation and normal amniotic fluid volume, group III had bilateral dilatation and oligohydramnios, group IV had nonurinary tract malformations in addition to urinary tract dilatation. Patients with normal amniotic fluid volume and either unilateral or bilateral fetal dilatation (groups I and II) had a good pregnancy outcome. Patients with oligohydramnios and bilateral dilatation had a poor pregnancy outcome. No intrauterine surgery or shunting was performed in any of the patients. The initial diagnosis of urinary tract dilatation led to the prenatal diagnosis of major nonurologic malformations (group IV) in 3 patients who also had a poor outcome. An algorithm is presented that reflects our experience with the management of these patients and could serve as a guide for others caring for similar patients.

Amniotic Fluid↗
PubMed1986

Dazoxiben, UK 38,485 and aspirin: duration of effect for preventing thrombotic sudden death in rabbits.

The purpose of this study was to compare the effects of dazoxiben (DAZ), UK 38,485 (UK) and aspirin (ASA) in the prevention of thrombotic sudden death in rabbits. In anesthetized male rabbits, sudden death was produced by intravenous administration of 0.75 mg/kg arachidonic acid (AA). AA increased plasma TxB2 levels from 0.20 +/- 0.10 ng/ml to 8.75 +/- 1.79 ng/ml and produced a 42% reduction in the number of circulating platelets. Death occurred in all animals within 5 minutes. Administration of DAZ (8.6 mumole/kg) 15 min before AA prevented the increase in plasma TxB2, the thrombocytopenia and sudden death while pretreatment with DAZ 2 hr before AA did not. The administration of UK (8.6 mumole/kg) 15 min. 4 hrs or 8 hrs before AA resulted in 100%, 67% and 33% survival, respectively. ASA (110 mumole/kg) administered 2 or 24 hrs before AA inhibited the increase in plasma TxB2 and prevented the fall in platelet counts. All animals pretreated with ASA survived. These data demonstrate that DAZ and UK have only a short to moderate duration of action in preventing AA-induced increases in plasma Tx levels and thrombocytopenia.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Interrelationships among human chorionic gonadotropin (hCG), 17 beta-estradiol, progesterone, and estriol in maternal serum: evidence for an inhibitory effect of the fetal adrenal on secretion of hCG.

In normal pregnancy, maternal serum hCG reaches a maximum concentration about 8-10 weeks after the last menstrual period and then decreases. To investigate the possibility that this decrease in hCG is produced by an inhibitory effect of steroids originating in the feto-placental unit, hCG, progesterone, 17 beta-estradiol, and estriol were determined by specific RIAs in 341 serum specimens obtained from 229 different pregnancies. Expressions for predicted hCG as a function of estimated trophoblastic mass and percent predicted hCG were determined to correct for the increase in hCG with increasing trophoblastic mass. The relationships between hCG and progesterone, 17 beta-estradiol, estriol, or estimated trophoblastic mass were not linear. Expression of the hCG data as percent predicted hCG produced linear relationships between hCG and each of the above steroids. Both hCG itself and percent predicted hCG were shown to have a negative regression on estriol (P less than 0.001) and a positive regression on progesterone (P less than 0.001), but not on 17 beta-estradiol (P greater than 0.05), in a multiple linear regression on all three steroids. These data suggest that hCG production is inhibited by a steroid originating in the fetal adrenal. This inhibitory effect plateaus in late pregnancy, allowing a minor late increase in hCG due to increasing trophoblastic mass.

Adrenal Glands↗
PubMed1983

Megaloblastic anemia after gastric bypass for obesity.

A megaloblastic anemia occurred in a middle-aged woman 6 years after a gastric bypass performed for obesity. Marked deficiencies of both vitamin B12 and folic acid were demonstrated. The Schilling test revealed that the vitamin B12 deficiency was due primarily to inadequate intrinsic factor. Vitamin and mineral deficiencies are relatively common long-term complications in gastric bypass patients, and result from multiple factors including restricted food intake, inadequate gastric digestion, and inadequate intrinsic factor. Bypass patients should receive vitamin-mineral supplements routinely and should have long-term periodic clinical and laboratory evaluation in order to prevent late hematological complications.

Anemia, Macrocytic↗
PubMed1981

Ankle arthrography.

Ankle arthrography allows radiologists to assess accurately the degree of damage caused by ankle sprains. Ankle sprains are a significant problem to a large number of people, particularly those who participate in sports. Proper care of these ankle injuries requires the combined expertise of many disciplines. Radiologists should be aware of the significance of these lesions and utilize all modalities, including plain films, stress films, and ankle arthrograms, when indicated, to obtain the exact pathologic diagnosis of severe sprains. The primary role of arthrography is to separate those patients who have moderate or severe sprains that may require surgery from those who will respond to more conservative therapy. Many orthopedists believe that combined lateral ligament tears, or any tear involving the deltoid ligament and perhaps the interosseous ligament, may require surgery. At the other end of the spectrum of ankle sprains, occasionally, one may not be able to distinguish between a very slight sprain and a more severe sprain with rupture of the ankle ligament. This is an important distinction, particularly in young athletes who would like to continue to play a competitive sport despite their injury. Utilizing arthrography, the orthopedic surgeon can suggest a more accurate prognosis as to whether the patient might be able to participate with proper taping. Obviously, if the patient has ruptured a ligament, it is not in the best interest of the patient to participate in a competitive sport without allowing a proper interval for healing. I heartily recommend arthrography of the ankle to any radiologist who is not yet utilizing this procedure. I believe that it can add significantly to the care of those patients who sustain ankle sprains.

Ankle Injuries↗
PubMed1980

Oxytocin challenge tests and urinary estriols in the management of high-risk pregnancies.

Three hundred sixty-two pregnant patients at risk for placental insufficiency were evaluated with the oxytocin challenge test (OCT) and urinary estriol determinations. The perinatal mortality in patients with positive tests was 6 times higher than the perinatal mortality in patients with negative tests. Expectant treatment of patients with a positive OCT was associated with a perinatal mortality 6 times higher than if immediate delivery was accomplished. A negative stress test was reassuring, as the risk of death in utero within a week of a negative test was only 0.3%. The combination of low estriol levels and positive OCT was quite ominous, while the presence of normal estriol levels provided reassurance of good perinatal outcome when expectant treatment of a patient with a positive OCT was undertaken. The overall perinatal mortality of the patients in this study was not different from that in the general obstetric population.

Cesarean Section↗
PubMed1980

Temporary submucosal cervical cerclage.

A submucosal, easily removable cervical cerclage was placed in 37 patients with cervical incompetence. The perinatal mortality rate compared favorably with reports using other techniques, and the cesarean section rate was not different from that in the overall obstetric population. In view of the absence of any complications, this technique would seem to be the cerclage of choice.

Adolescent↗
PubMed1980

Ambulatory care of the pregnant diabetic.

One hundred eight pregnancies in 98 insulin-dependent diabetic women were managed according to a strict protocol calling for weekly postprandial blood sugar determinations, frequent prenatal contacts, and placental evaluation. Patients were cared for on an ambulatory basis with an average of 1 hospitalization during pregnancy exclusive of delivery. There were no fetal deaths and only 1 neonatal death related to diabetes, for a corrected perinatal mortality of 0.97%. White's classification was not helpful in identifying perinatal risks. The incidence of both perinatal and maternal morbidity was high; however, complications were not serious and the overall outcome was acceptable. In view of the financial and social benefits to patients, it is recommended, that an ambulatory approach to care of the pregnant diabetic patient be used and when feasible it should be the method of choice.

Adult↗
PubMed1979

Effect of diabetes mellitus on amniotic fluid lecithin/sphingomyelin ratio and respiratory distress syndrome.

Ninety-eight insulin-dependent diabetic patients were cared for during 108 pregnancies following an ambulatory program aimed at close control of blood sugar levels. The incidence of respiratory distress syndrome (RDS) in these patients was not different from that in nondiabetic patients. Fetal pulmonary maturity seemed to progress at a normal rate as evidenced by an equal incidence of mature lecithin/sphingomyelin (L/S) ratios at various stages of gestation in diabetic and nondiabetic patients. There was no evidence that Class B and C diabetic patients have delayed fetal lung maturation or that Class E, F, and R patients have accelerated maturation. It is concluded that careful metabolic control of the pregnant diabetic patient results in a normal process of fetal pulmonary maturation without increased risk of RDS.

Amniotic Fluid↗
PubMed1979

Evaluation of a program of bed rest in the treatment of chronic hypertension in pregnancy.

Sixty-six patients with chronic hypertension were cared for during a total of 72 pregnancies. Patients were treated at home primarily by greater than or equal to 4 hours of bed rest daily in the left recumbent position. Only patients whose diastolic blood pressures remained greater than 110 mmHg were treated with hydralazine (Apresoline, Ciba). With this plan of treatment there were only 3 perinatal deaths for an uncorrected perinatal mortality of 4.1% (1.4% corrected). Twenty-nine percent of the patients had babies that were small for gestational age, 13.8% had positive oxytocin challenge tests, and 36.8% developed superimposed preeclampsia. When compared with the outcome of previous pregnancies, the program of bed rest lowered perinatal mortality from 16.8 to 8.8%. Thus, it is suggested that bed rest together with the avoidance of diuretics and the judicious use of hydralazine results in the most favorable fetal outcome.

Bed Rest↗