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Biomedical subjects

A K Pedersen

Publications and source records attributed to A K Pedersen.

At least 55 records · Page 3Linked to original sources
PubMed1994

Complete fracture-dislocation of the atlantoaxial complex: case report and recommendations for a new classification of dens fractures.

A 77-year-old man fell and sustained a fracture-dislocation of the atlantoaxial complex with 20 mm of posterior displacement. Initial and repeat examinations failed to diagnose the fracture-dislocation, which was first diagnosed by a magnetic resonance imaging study 16 weeks after the injury and after the patient had developed a profound myelopathy. The patient was treated by a C2 decompressive laminectomy and an in situ posterior fusion with iliac bone graft and internal fixation with gradual resolution of his myelopathy. Postoperatively he developed respiratory problems and persistent difficulties swallowing, believed to be at least partly due to cranial nerve involvement. A new classification system for dens fractures is suggested.

Accidents↗
PubMed1993

Effects of fish oil supplementation in the third trimester of pregnancy on prostacyclin and thromboxane production.

OBJECTIVE: Disturbance in thromboxane and prostacyclin biosynthesis has been observed in preeclampsia. We studied whether fish oil supplementation in late pregnancy interferes with maternal and fetal production of thromboxane A2 and prostacyclin I2. STUDY DESIGN: Forty-seven women in the thirtieth week of pregnancy were randomly assigned in a ratio of 2:1:1 to receive fish oil (2.7 gm of n-3 fatty acid per day [Pikasol], or either olive oil or no oil supplementation as controls. Metabolites of thromboxane A2 and A3 and of prostacyclin I2 and I3 were quantified by mass spectrometry methods in serum and urine, respectively. Maternal serum and urine were sampled at baseline, in the thirty-third and thirty-seventh weeks of pregnancy. Fetal serum was sampled at delivery. RESULTS: At the thirty-seventh week the mean concentrations of the eicosapentaenoic-derived metabolites, thromboxane B3 and prostacyclin I3, was twofold to threefold higher (p < 0.001) in the group receiving fish oil compared with combined control groups. There were no significant effects of fish oil on the prostacyclin I2 metabolite, although there was a trend toward a reduction in thromboxane B2 in this group. In umbilical cord blood the mean concentration of thromboxane B2 was lowest in the group receiving fish oil (p = 0.03). CONCLUSIONS: Fish oil was metabolized to the eicosapentaenoic acid-derived eicosanoids thromboxane A3 and prostacyclin I3 in pregnant women. Correspondingly, analog products of arachidonic acid tended to be depressed. It remains to be established whether these biochemical effects will prove beneficial in the prevention or treatment of preeclampsia and intrauterine growth retardation.

Adult↗
PubMed1992

A posteroseptal accessory pathway located in a coronary sinus aneurysm: diagnosis and radiofrequency catheter ablation.

A coronary sinus aneurysm was diagnosed by means of echocardiography, coronary sinus contrast angiography, coronary angiography, and nuclear magnetic resonance imaging in a patient with Wolff-Parkinson-White syndrome caused by a posteroseptal accessory pathway. Percutaneous radiofrequency current catheter ablation performed in the isthmus of the coronary sinus aneurysm was successful.

Adult↗
PubMed1992

Nonpharmacologic treatment of supraventricular and ventricular tachyarrhythmias. A review of 249 consecutive patients.

Incapacitating or life-threatening tachyarrhythmias were treated nonpharmacologically in 249 patients from 1982 to 1991. Among 92 patients surgically treated for supraventricular tachycardia the cure rate was 93% and the complication rate 12%. Radiofrequency catheter ablation gave an equal cure rate in 51 patients, but with no major complications or mortality. Direct-current catheter ablation of the His bundle was successful in 96% of 27 patients with drug-refractory atrial fibrillation or other supraventricular tachyarrhythmias. Among 64 patients undergoing surgery for ventricular tachycardia/ventricular fibrillation, the perioperative mortality was 9%, estimated 5-year survival 69% and estimated 5-year freedom from the preoperative arrhythmias 72%. Of 18 patients treated with implantable cardioverter defibrillator, three (18%) died of heart failure during follow-up. Nonpharmacologic treatment of tachyarrhythmias is concluded to be effective and often definitively curative. The safety-risk ratio is improving as new treatment modalities are developed.

Adolescent↗
PubMed1991

Antiischemic and metabolic effects of glutamate during pacing in patients with stable angina pectoris secondary to either coronary artery disease or syndrome X.

The effects of glutamate on anginal threshold, cardiac metabolism and hemodynamics were studied in 11 patients with stable angina pectoris, positive stress test results, and pacing-induced myocardial lactate release due to coronary artery disease (CAD) (n = 9) or syndrome X (n = 2). Data were obtained before, during and after 2 identical periods of coronary sinus pacing, the second being preceded by an intravenous injection of monosodium glutamate 1.2 (n = 7) or 2.5 (n = 4) mg/kg body weight. After glutamate administration, pacing time to onset of angina increased from mean +/- standard deviation 103 +/- 53 to 166 +/- 71 seconds (p less than 0.01) and ST-segment depression after pacing decreased from 2.3 +/- 1.0 to 1.6 +/- 1.1 mm (p less than 0.01). Arterial glutamate concentration increased 60% (p less than 0.01) after the low dose and 150% (p less than 0.01) after the high dose of glutamate. Regardless of dose, myocardial glutamate uptake increased by 25% (p less than 0.01). Pacing-induced cardiac release of lactate diminished 50% (p less than 0.05), whereas the releases of xanthine and hypoxanthine were unchanged by glutamate. Arterial free fatty acids decreased 20% (p less than 0.01). Circulating levels and cardiac exchanges of alanine, glucose and citrate were unchanged. Glutamate did not influence heart rate, arterial blood pressure, coronary blood flow, coronary vascular resistance or myocardial oxygen consumption. One patient complained of short-lasting burning sensations after receiving the high glutamate dose. In conclusion, augmented provision of glutamate enhances pacing tolerance in stable angina, presumably by a metabolic improvement of cardiac energy production during ischemia.

Adult↗
PubMed1990

Flecainide acetate in atrial flutter and fibrillation. The arrhythmogenic effects.

The arrhythmogenic effects of flecainide in atrial fibrillation and flutter were assessed in a consecutive material of 100 patients without severe heart failure (NYHA class I or II). Severe arrhythmogenic events occurred in 9% (4-16%) of the patients: within the first 5 days of treatment in seven patients, and in two patients after 60 and 240 days of flecainide treatment. Patients with proarrhythmic events tended to be older and to have a longer QRS duration. Following flecainide therapy conversion to sinus rhythm was achieved in 21 of 43 patients (49%) with atrial fibrillation and in 10 of 29 (34%) with atrial flutter. It is concluded that flecainide, although an effective antiarrhythmic drug, has potential proarrhythmic effects and therefore cautious use of this drug is mandatory.

Aged↗
PubMed1988

Spondylolysis and spondylolisthesis. Treatment by internal fixation and bone-grafting of the defect.

Eighteen patients who had symptomatic spondylolysis or Grade-I spondylolisthesis, and whose symptoms had not been relieved by non-operative treatment, were operated on using the Buck method for bone-grafting and internal fixation of the defect of the pars interarticularis with screws. There were six male and twelve female patients and the average age was twenty years (range, fourteen to thirty-eight years). The amount of slipping ranged from zero to ten millimeters. After an average period of follow-up of forty-one months (range, twenty-four to seventy-two months), the result was excellent in ten, good in five, and poor in three patients. Thus, a satisfactory result was obtained in 83 per cent of the patients.

Adolescent↗
PubMed1985

Preparation and analysis of deuterium-labeled aspirin: application to pharmacokinetic studies.

Inhibition of endogenous prostacyclin and thromboxane biosynthesis by aspirin is critically dose-dependent in humans. Gastrointestinal and hepatic hydrolysis may limit systemic availability of aspirin, especially in low doses, perhaps contributing to the biochemical selectivity of aspirin. Existing analytical methods do not permit determination of systemic bioavailability when low (less than 100 mg) doses of aspirin are administered. Deuterium-labeled aspirin (2-acetoxy[3,4,5,6-2H4]benzoic acid) was synthesized from salicylic acid by catalytic exchange and subsequent acetylation. Analysis of the compounds as benzyl esters by GC-MS followed extractive alkylation from plasma. Heptadeuterated compounds were used as internal standards. Simultaneous administration of tetradeuterated aspirin intravenously with native aspirin orally to anesthetized dogs permitted kinetic studies of both aspirin and salicylic acid. The sensitivity of the method is superior to published methods using HPLC and, thus, more applicable to studies of low dose aspirin. Pulse administration of stable isotope-labeled aspirin permits detailed and repeated studies of dose-related aspirin pharmacokinetics in humans.

Animals↗
PubMed1985

Cyclooxygenase inhibition, platelet function, and metabolite formation during chronic sulfinpyrazone dosing.

The inhibitory effects of sulfinpyrazone are more marked ex vivo than in vitro, suggesting biotransformation to potentially active metabolites such as the sulfide and sulfone metabolites. As a platelet inhibitor, the sulfide metabolite is 10 times as potent as the parent and because of its long t1/2, the former may lead to cumulative inhibition of platelet function in vivo during chronic sulfinpyrazone dosing. In our study, healthy subjects received sulfinpyrazone, 200 mg four times a day, for 6 days. Plasma levels of the sulfide metabolite rose slightly from 2.1 +/- 0.8 micrograms/ml 12 hr after the fourth dose to 2.8 +/- 0.8 microgram/ml 12 hr after the twenty-fourth dose. This was associated with increasing inhibition of ex vivo platelet aggregation induced by platelet-activating factor during the dosing period, but inhibition of arachidonic acid-induced aggregation did not increase cumulatively during dosing and collagen-induced aggregation was not inhibited. Inhibition of platelet aggregation was no longer evident 24 hr after the final dose of sulfinpyrazone. The effects of sulfinpyrazone on cyclooxygenase activity were assessed by measurement of thromboxane B2 production by thrombin-stimulated platelets ex vivo and urinary excretion of the major prostacyclin metabolite 2,3-dinor-6-keto-PGF1 alpha. During sulfinpyrazone dosing, thromboxane formation and prostacyclin biosynthesis were correspondingly lowered 50% to 60%. The extent of this depression was of the same order on days 2 and 5 of dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

The biochemical pharmacology of thromboxane synthase inhibition in man.

Selective inhibitors of thromboxane synthase have two theoretical advantages over inhibitors of the cyclooxygenase enzyme as potential antithrombotic compounds. First, they do not prevent formation of prostacyclin, a platelet-inhibitory, vasodilator compound, coincident with inhibiting thromboxane biosynthesis. Second, the prostaglandin endoperoxide substrate that accumulates in the platelet in the presence of thromboxane synthase inhibition may be donated to endothelial prostacyclin synthase at the site of platelet-vascular interactions (endoperoxide "steal"). Selective inhibition of thromboxane biosynthesis coincident with enhanced prostacyclin formation in vivo has been observed after administration of these compounds to man. Despite these attractive features and the efficacy of these compounds in diverse short-term animal preparations of thrombosis, investigations of their efficacy in human disease have proven disappointing. This may reflect on the importance of thromboxane A2 in the diseases that have been investigated. Alternatively, the lack of drug efficacy may have resulted from either incomplete suppression of thromboxane biosynthesis and/or substitution for the biological effects of thromboxane A2 by prostaglandin endoperoxides during long-term dosing studies. Given that selective inhibition of thromboxane formation can be approached with aspirin, the particular value of these compounds is dependent on enhancing prostacyclin formation. Aspirin inhibits thromboxane-dependent platelet activation, but many platelet agonists are likely to act in concert in vivo and prostacyclin inhibits platelet aggregation induced by both thromboxane-dependent and thromboxane-independent mechanisms. To test the hypothesis that thromboxane synthase inhibitors are efficacious in human disease, compounds of longer duration of action are required. Combination with antagonists of the prostaglandin/thromboxane A2 receptor may be necessary to reveal their full beneficial action.

Clinical Trials as Topic↗
PubMed1984

Dose-related kinetics of aspirin. Presystemic acetylation of platelet cyclooxygenase.

When aspirin is administered by mouth in low doses, poor systemic bioavailability may contribute to its apparent dose-related "selective inhibition" of thromboxane A2 formation. Systemic bioavailability of orally administered aspirin is necessary to inhibit prostacyclin synthesis by systemic vascular endothelium, whereas cumulative inhibition of thromboxane A2 formation by platelets may occur in the presystemic (portal) circulation. We simultaneously administered unlabeled aspirin orally and deuterium-labeled aspirin intravenously in five healthy volunteers. This permitted an estimation of the bioavailability of an oral dose from the ratio of plasma drug concentration-time curves for the labeled and the unlabeled species. Systemic bioavailability ranged from 46 to 51 per cent of single oral doses of 20, 40, 325, and 1300 mg of aspirin. Bioavailability was similar after single-dose and long-term oral administration of 325 mg. Thromboxane B2 formation in serum ex vivo after oral administration of 20 mg of unlabeled aspirin was reduced 39 per cent before aspirin was detected in the systemic circulation. Furthermore, incubation of simulated peak plasma aspirin concentrations in whole blood in vitro underestimated the inhibition of thromboxane B2 ex vivo after oral administration of 20 or 40 mg of unlabeled aspirin. These data are consistent with presystemic inhibition of platelets by aspirin and suggest that biochemical "selectivity" might be enhanced by slow administration of very low doses of aspirin, thereby optimizing conditions for cumulative, presystemic acetylation of platelet cyclooxygenase and inhibition of thromboxane formation.

Acetylation↗
PubMed1984

Increased prostacyclin biosynthesis in patients with severe atherosclerosis and platelet activation.

Prostacyclin is a potent vasodilator and platelet inhibitor produced by vascular endothelium. Endogenous production of prostacyclin under physiologic conditions is extremely low, far below the capacity of vascular tissue to generate this substance in response to stimulation in vitro. This may reflect a low frequency or intensity of stimulation of prostacyclin production. We postulated that if prostacyclin does act as an endogenous platelet-inhibitory agent, it should be produced in greater amounts in a clinical setting in which platelet-vascular interactions are likely to be increased. To test this hypothesis, we examined prostacyclin biosynthesis in patients with severe atherosclerosis and evidence of platelet activation in vivo. Excretion of 2,3-dinor-6-keto-prostaglandin F1 alpha, a major urinary prostacyclin metabolite, was significantly higher in 9 patients with severe atherosclerosis and evidence of platelet activation (251 to 1859 pg per milligram of creatinine) than in 54 healthy volunteers (45 to 219 pg per milligram of creatinine; P less than 0.001). This difference represented an alteration in biosynthesis rather than in metabolism, since the fractional conversion of infused prostacyclin to the dinor metabolite was identical in both groups. Prostacyclin production may be low in healthy persons because there is almost no stimulus for its production but enhanced in patients with severe atherosclerosis as a consequence of platelet interactions with endothelium or other vascular insults. These observations are compatible with a role for prostacyclin as a local regulator of platelet-vascular interactions.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Systemic availability of acetylsalicylic acid in normal men and women and its effect on in vitro platelet aggregability.

The systemic availability of acetylsalicylic acid (ASA) after oral ingestion of 1 g in an effervescent formulation was 16.3 +/- 2.0% and 16.9 +/- 3.2% of the ingested dose in normal women and men, respectively. The average plasma half-life of ASA in each sex was also identical at 18.5 +/- 1.4 and 18.1 +/- 1.2 min, respectively. The inhibitory effect of ASA on collagen-induced platelet aggregation in vitro on blood from both sexes was studied. The IC50 was 23.9 +/- 2.9 micrograms/ml in females and 22.5 +/- 2.7 micrograms/ml in males, which did not differ significantly. The inhibition by salicylic acid (SA) of the antiaggregatory effect of ASA was similar in both sexes with increases in IC50 to 33.5 +/- 5.1 micrograms/ml in females (p less than 0.02) and to 29.5 +/- 3.8 micrograms/ml in males (p less than 0.05). It is concluded that the observed sex-difference in the antithrombotic effect of ASA cannot be explained neither by differences between females and males in the pharmacokinetic properties of ASA after oral ingestion, nor by differences in the in vitro effect of ASA on the platelet aggregation induced by collagen.

Adult↗