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Biomedical subjects

E Mortensen

Publications and source records attributed to E Mortensen.

At least 19 recordsLinked to original sources
PubMed2001

Review article: the gastrointestinal safety profile of rofecoxib, a highly selective inhibitor of cyclooxygenase-2, in humans.

Highly selective inhibitors of cyclooxygenase-2, such as rofecoxib, are hypothesized to have an improved gastrointestinal tolerability and safety profile compared with non-selective NSAIDs, which inhibit cyclooxygenase-1 and cyclooxygenase-2 non-selectively. This paper reviews data from randomized, double-blind, placebo-controlled studies which investigated the effects of rofecoxib and NSAIDs on the human gastrointestinal tract. In healthy subjects, rofecoxib 25 mg and 50 mg daily had no effect on gastric mucosal prostaglandin synthesis, whilst naproxen 1000 mg daily caused a 70% reduction. Therapeutic doses of rofecoxib 25 mg and 50 mg daily did not increase intestinal permeability or faecal blood loss in healthy subjects, whereas increases in both measures were seen with indometacin 150 mg or ibuprofen 2400 mg. A supra-therapeutic dose of rofecoxib (250 mg) given daily for 7 days did not induce an increase in gastroduodenal erosions in healthy subjects, whilst increased numbers of erosions were found in subjects given ibuprofen 2400 mg or aspirin 2600 mg. The endoscopic findings in healthy subjects were confirmed in two 6-month clinical studies involving 1516 patients with osteoarthritis; the incidences of ulcers following rofecoxib 25 mg or 50 mg daily were similar to placebo and less than ibuprofen 2400 mg. The advantage of rofecoxib over NSAIDs in these studies appears to translate into clinically relevant benefits; an analysis of 5435 patients with osteoarthritis found a significantly lower incidence of gastrointestinal perforations, ulcers and bleeds in patients taking rofecoxib compared with patients taking NSAIDs. Overall, the findings from these studies suggest that, as a result of cyclooxygenase-1 sparing, rofecoxib is significantly less gastrotoxic than non-selective NSAIDs, and may not differ from placebo.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Influence of risk factors on endoscopic and clinical ulcers in patients taking rofecoxib or ibuprofen in two randomized controlled trials.

BACKGROUND: Highly selective inhibitors of the inducible cyclooxygenase-2 enzyme (coxibs) have been associated with less gastrotoxicity than nonselective NSAIDs in clinical studies. AIM: To evaluate the influence of risk factors for NSAID-induced gastrotoxicity on endoscopic and clinical ulcers in patients taking rofecoxib or ibuprofen. METHODS: We analysed pooled data from two identical double-blind, randomized, 12-week endoscopy studies which compared the gastroduodenal toxicity of placebo (n=371), rofecoxib 25 mg (n=390), rofecoxib 50 mg (n=379), and ibuprofen 2400 mg daily (n=376) in patients with osteoarthritis. The potential risk factors evaluated were: age (< 65, > or = 65 years), sex, race (white, nonwhite), Helicobacter pylori status, presence of gastroduodenal erosions at baseline, a history of upper gastrointestinal disease, prior NSAID use within 30 days of study entry, and smoking. We also evaluated these factors for possible association with the development of clinically-evident gastrointestinal perforations, ulcers or bleeds over 12 weeks. RESULTS: Across all treatment groups, the likelihood of detecting endoscopic ulcers, or of clinical presentation with a bleed, over 12 weeks was increased approximately 4-5-fold in patients with previous upper gastrointestinal disease (relative risk [95% confidence interval] of 4.2 [2.5, 7.1] for endoscopic ulcers; 3.8 [1.4, 10.6] for bleeds), or those with gastroduodenal erosions at baseline endoscopy (relative risk of 4.4 [2.6, 7.5] for endoscopic ulcers; 5.0 [1.9, 13.5] for bleeds). H. pylori infection did not increase the risk of endoscopic ulcers or bleeds (relative risk of 1.1 [0.8, 1.6] for endoscopic ulcers; 0.3 [0.1, 0.9] for bleeds). The risk factor sub-group effects were constant across all treatment groups, and the significantly higher incidence of ulcers with ibuprofen as compared to rofecoxib and placebo was maintained in all risk factor subgroups. CONCLUSIONS: Gastroduodenal erosions at baseline and a clinical history of upper gastrointestinal disease, but not H. pylori colonization, increased the risk for endoscopically-detected ulcers and clinical bleeds. Rofecoxib did not magnify the risk in any of the patient subgroups studied.

Aged↗
PubMed2000

Comparison of the effect of rofecoxib (a cyclooxygenase 2 inhibitor), ibuprofen, and placebo on the gastroduodenal mucosa of patients with osteoarthritis: a randomized, double-blind, placebo-controlled trial. The Rofecoxib Osteoarthritis Endoscopy Multinational Study Group.

OBJECTIVE: This randomized, double-blind study tested the hypothesis that rofecoxib, a drug that specifically inhibits cyclooxygenase 2, would cause fewer gastroduodenal ulcers than ibuprofen (in a multicenter trial), and its side effects would be equivalent to those of placebo (in a prespecified analysis combining the results with another trial of identical design). METHODS: Seven hundred seventy-five patients with osteoarthritis were randomized to receive rofecoxib at a dosage of 25 mg or 50 mg once daily, ibuprofen 800 mg 3 times daily, or placebo. Gastroduodenal ulceration was assessed by endoscopy at 6, 12, and (for active treatment) 24 weeks. The primary and secondary end points were the incidence of gastroduodenal ulcers at 12 and 24 weeks, respectively. RESULTS: Ulcers were significantly less common (P < 0.001) following treatment with rofecoxib (25 mg or 50 mg) than with ibuprofen after 12 weeks (5.3% and 8.8% versus 29.2%, respectively) or 24 weeks (9.9% and 12.4% versus 46.8%, respectively). In the combined analysis, the 12-week ulcer incidence with 25 mg rofecoxib (4.7%) and with placebo (7.3%) satisfied prespecified criteria for equivalence. CONCLUSION: At 2-4 times the therapeutically effective dose, rofecoxib caused fewer endoscopically detected ulcers than did ibuprofen. Rofecoxib at a dose of 25 mg (the highest dose recommended for osteoarthritis) satisfied prespecified criteria for equivalence to placebo.

Cyclooxygenase Inhibitors↗
PubMed1997

Cardiovascular effects of MnDPDP and MnCl2 in dogs with acute ischaemic heart failure.

PURPOSE: To examine the cardiovascular effects of MnDPDP in a model of acute heart failure in the dog, and to compare these effects with those of MnCl2. MATERIAL AND METHODS: The study involved slow i.v. infusion of either 10, 60 and 300 mumol/kg of MnDPDP, or 1, 6 and 30 mumol/kg MnCl2, in increasing doses to groups of 5 dogs. Acute ischaemic heart failure was first induced by injection of polystyrene microspheres (50 +/- 10 microns) into the left coronary artery until a stable left ventricular end-diastolic pressure of approximately 20 mm Hg was achieved. The following test parameters were measured: left ventricular end-diastolic pressure; the first derivatives of maximum rate of left ventricular contraction and relaxation; mean aortic pressure; pulmonary artery pressure; right atrial pressure; cardiac output; heart rate; QT-time; PQ-time; QRS-width; and plasma catecholamines. RESULTS: Slow infusion of MnDPDP at doses up to and including 12 times the clinical dose was well tolerated in dogs without further depression of cardiovascular function during acute ischaemic heart failure. At 300 mumol/kg, i.e. 60 times the human dose, only minor haemodynamic and electrophysiological effects were seen, and these were similar to those seen after administration of 30 mumol/kg MnCl2. CONCLUSION: The present study suggests that slow infusion of MnDPDP should not cause further deterioration of cardiac function in patients with heart failure.

Acute Disease↗
PubMed1996

[Tamoxifen and endometrial cancer. A case report].

Tamoxifen is an oestrogen antagonist with partial agonistic effects that is used extensively in the treatment of mammary carcinoma. We report a case of an 80 year old woman who was operated on for carcinoma of the mammary gland and developed endometrial carcinoma after ten years of tamoxifen treatment. Tamoxifen has been noted for its reportedly low incidence of side effects. Since 1985, however, several reports have associated tamoxifen with higher risk of endometrial carcinoma. We also review the relevant literature published during the last decade.

Adenocarcinoma↗
PubMed1995

Transformation of o-xylene to o-methyl benzoic acid by a denitrifying enrichment culture using toluene as the primary substrate.

A highly enriched denitrifying mixed culture transformed o-xylene co-metabolically along with toluene by methyl group oxidation. o-Methyl benzaldehyde and o-methyl benzoic acid accumulated transiently as metabolic products of o-xylene transformation. Transformation of o-methyl benzyl alcohol and o-methyl benzaldehyde occurred independently of toluene degradation and resulted in the formation of a compound coeluting with o-methyl benzoic acid on a gas chromatograph. The co-metabolic relationship between toluene and o-xylene could be attributed to a mechanism linked to the initial oxidation of the methyl group.

Bacteria, Anaerobic↗
PubMed1995

Isolation by anion-exchange of immunologically and enzymatically active human islet glutamic acid decarboxylase 65 overexpressed in Sf9 insect cells.

The enzyme L-glutamic acid decarboxylase is a major autoantigen of the beta cell. Autoantibodies against this enzyme are observed before the onset of insulin-dependent diabetes mellitus (IDDM) in man and may be of predictive value. There is evidence that this enzyme is involved in the development of autoimmune diabetes in animals. In order to facilitate the investigation of the role of L-glutamine acid decarboxylase in IDDM, we expressed the 65 kDa isoform of human islet L-glutamic acid decarboxylase in insect cells using a baculovirus-based vector. The material was expressed at high levels (up to 50 mg/l of cells). Partially purified metabolically labelled L-glutamic acid decarboxylase bound to immunoglobulins in the sera from 20 of 49 subjects with newly-diagnosed IDDM. The enzyme was isolated in high yields (up to 26 mg/l cell culture) with fully maintained enzymatic activity by either ion-exchange chromatography or immunoaffinity chromatography. Purified L-glutamic acid decarboxylase inhibited the binding of radioactive L-glutamic acid decarboxylase, prepared by in vitro translation of mRNA, to immunoglobulins in the sera of subjects with IDDM. Recombinant human islet L-glutamic acid decarboxylase, isolated from Sf9 cells, is a suitable material for the large scale investigation of the utility of this enzyme in the prediction and prevention of autoimmune diabetes.

Adolescent↗
PubMed1995

Contrast-medium-induced ventricular fibrillation: arrhythmogenic mechanisms and the role of antiarrhythmic drugs in dogs.

RATIONALE AND OBJECTIVES: Small electrolyte additions to a nonionic contrast medium reduce the risk of ventricular fibrillation (VF) during wedged catheter injection of a contrast medium. The current study was designed to further investigate contrast-medium-induced VF by studying the effect of pretreatment with different antiarrhythmic drugs. METHODS: During a simulated wedged catheter situation, iohexol was injected into the anterior descending branch of the left coronary artery in five open-chest, anesthetized dogs pretreated with lidocaine, propranolol, amiodarone, almokalant, or verapamil. RESULTS: Wedging the catheter for 60 sec did not induce VF. However, all 15 wedged catheter injections with iohexol induced VF within 28 sec (19 +/- 1 [mean +/- standard error of the mean]) despite pretreatment with antiarrhythmic drugs. Prior to VF, conduction was slowed and monophasic action potential duration lengthened in the contrast-medium-perfused myocardium, although no significant changes occurred in the control area. CONCLUSION: The combination of catheter wedging and long-lasting contrast medium injection has a high risk of causing VF. Although adding a small amount of electrolytes to nonionic contrast media can reduce the risk of VF, antiarrhythmic drug therapy may not have a protective effect.

Action Potentials↗
PubMed1995

Additive hemodynamic and electrophysiologic effects of repeated intracoronary contrast media injections in dogs with heart failure.

RATIONALE AND OBJECTIVES: We investigated the cardiac effects of single and repeated contrast media injections in dogs with heart failure and compared the effects of iohexol with iohexol supplemented with electrolytes (30 mmol/l NaCl, 0.15 mmol/l CaCl2, 0.9 mmol/l KCl, and 0.1 mmol/l MgCl2; iohexol + electrolytes [IPE]). Although it has a higher osmolality than iohexol, IPE appears to be safer when injected through a wedged catheter. METHODS: Acute ischemic heart failure was induced by injections of small plastic microspheres into the left coronary artery of 16 anesthetized dogs. Iohexol, IPE, and Ringer acetate were injected into the left coronary artery either as a 5-ml single injection or repeatedly five times, once every 10th second. RESULTS: Single injections of iohexol and IPE induced small hemodynamic and electrophysiologic effects. However, repeated injections of iohexol and IPE increased the maximum rate of isovolumetric contraction by 46% and 36%, reduced heart rate by 8% and 7%, and lengthened QTc (the Q-T interval corrected for heart rate) time by 44 and 39 msec, respectively. No statistically significant differences were found in a comparison of IPE and iohexol. CONCLUSION: During heart failure, repeated injections of iohexol and IPE induced similar additive hemodynamic and electrophysiologic effects without inducing arrhythmias or serious hemodynamic changes.

Animals↗
PubMed1995

Diltiazem does not increase ventricular fibrillation threshold during hypothermia.

This study was designed to investigate whether the calcium channel blocker diltiazem affects the threshold for ventricular fibrillation during hypothermia in dogs. Ten dogs were cooled from 37 to 25 degrees C and rewarmed to 37 degrees C. The threshold for ventricular fibrillation was determined at body temperatures 37, 34, 31, 28 and 25 degrees C by programmed electrical stimulation using a stimulation protocol which involved application of maximal five extrastimuli. At 25 degrees C, six dogs were given an i.v. bolus dose of 100 micrograms.kg-1 followed by a continuous infusion of 100 micrograms.kg-1.h-1 of diltiazem hydrochloride. The other four dogs, were given no drugs at 25 degrees C and served as a control group. The dogs were rewarmed, and the stimulus protocol was performed at the same temperatures as during cooling. Cooling from 37 to 25 degrees C reduced the threshold for ventricular fibrillation in both groups. Heart rate were reduced, monophasic action potential duration at the apex and base of the heart increased from 167 +/- 5 ms to 469 +/- 17 ms and from 164 +/- 5 ms to 466 +/- 17 ms, respectively, when the temperature was reduced. The ventricular effective refractory period increased from 176 +/- 9 ms at 37 degrees C to 472 +/- 15 ms at 25 degrees C. Cooling increased QRS time on the ECG from 55 +/- 4 ms to 138 +/- 13 ms. Addition of diltiazem at 25 degrees C did not affect the threshold for ventricular fibrillation during rewarming. Further, diltiazem at 25 degrees C did not affect the heart rate or refractoriness.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1994

Effect of bretylium tosylate on ventricular fibrillation threshold during hypothermia in dogs.

How bretylium tosylate affected the ventricular fibrillation threshold, electrophysiological parameters, and plasma catecholamine levels during hypothermia in dogs was studied. Threshold for ventricular fibrillation was determined by programmed electrical stimulation using a stimulation protocol that involved applying a maximum of five extrastimuli at body temperatures 37, 34, 31, 28, and 25 degrees C, and at the same temperatures during rewarming. Electrocardiogram, epicardial monophasic action potentials (MAP), and electrograms were recorded, and ventricular effective refractory period (VERP) was determined at each of the above temperatures. In one group (n = 7), a bolus dosage of bretylium tosylate (BT), 6 mg/kg body wt, was administered at 25 degrees C before rewarming. Another group (n = 4) was exposed to cooling and rewarming without addition of BT. Cooling to 25 degrees C reduced ventricular fibrillation threshold linearly, reduced heart rate, increased VERP and MAP, and slowed myocardial conduction velocity in both groups. There was no overall increase in plasma catecholamine levels during cooling. Addition of BT at 25 degrees C increased ventricular fibrillation threshold during rewarming compared with cooling. Addition of BT at 25 degrees C increased VERP by +/- 32 milliseconds and the corrected JT time by 0.06 +/- 0.02 seconds. VERP and JTc increased during rewarming with BT compared with cooling with no drug. BT had no effect on conduction velocity, and plasma catecholamine levels were not reduced. The antiarrhythmic effect of BT during hypothermia was attributed to an increased wavelength of refractoriness by its increase in the refractory period. This increased wavelength of refractoriness may prevent excitable gaps or increase circuit pathway in the setting of reentry arrhythmias.

Action Potentials↗
PubMed1994

Experimental hypothermia: effects of core cooling and rewarming on hemodynamics, coronary blood flow, and myocardial metabolism in dogs.

Conflicting results have been reported as to the extent that cardiovascular function can be reestablished after rewarming from hypothermia. We measured hemodynamic function, myocardial metabolism and tissue water content in dogs core-cooled to 25 degrees C and later rewarmed. At 25 degrees C left ventricular (LV) systolic pressure (LVSP) was 54% +/- 4%, maximum rate of LV pressure rise (LV dP/dtmax) 44% +/- 5%, aortic pressure (AOP) 50% +/- 6%, heart rate (HR) 40% +/- 0%, cardiac output (CO) 37% +/- 5%, myocardial blood flow (MBF) 34% +/- 5%, and myocardial oxygen consumption (MVO2) 8% +/- 1%, compared to precooling. Stroke volume (SV) and LV end-diastolic pressure (LVEDP) were unchanged. As normothermia (37 degrees C) was reestablished, the depression of cardiac function and myocardial metabolism remained the same as that at 25 degrees C: LVSP 71% +/- 6%, LV dP/dtmax 73% +/- 7%, SV 60% +/- 9%, AOP 70% +/- 6%, CO 57% +/- 9%, MBF 53% +/- 8%, and MVO2 44% +/- 8% HR, in contrast, recovered to precooling values. The arterial concentrations of glucose and free fatty acids (FFA) did not change significantly during the experimental period, whereas an increase in lactate of nonmyocardial origin appeared after rewarming. Increased myocardial contents of creatine phosphate and water were found during both hypothermia and rewarming. The present study demonstrates a persistent depression of cardiac function after hypothermia and rewarming in spite of adequate energy stores. Thus, a direct influence on myocardial contractile function by the cooling and rewarming process is suggested.

Adenosine Triphosphate↗
PubMed1993

Chromosomal breakage, endomitosis, endoreduplication, and hypersensitivity toward radiomimetric and alkylating agents: a possible new autosomal recessive mutation in a girl with craniosynostosis and microcephaly.

A high frequency of spontaneous chromosomal breakage, endomitosis, endoreduplication and hypersensitivity toward both the alkylating agent Trenimon and the radiomimetric drug bleomycin was observed in phytohemagglutinin-stimulated peripheral lymphocytes from a girl with craniosynostosis, microcephaly, ptosis, bird-like facies, and moderate mental retardation. We also observed abnormal chromosomal spiralization and some aspects of abnormal cellular division. Several fruitless attempts were made to establish a cell line. The parents were consanguineous, supporting the existence of a new, rare, autosomal, recessive condition in man. The mutation might involve a gene involved in DNA repair and/or regulation of the mitotic cycle.

Adult↗
PubMed1992

Hemodynamic effects of d-sotalol in acute ischemic heart failure in dogs.

This study was designed to determine the hemodynamic effects of the class III antiarrhythmic agent d-sotalol in acute ischemic heart failure at concentrations that prolong ventricular repolarization. In pentobarbital-anesthetized open-chest dogs, heart failure was induced by microembolization of the area supplied by the main left coronary artery until a stable left ventricular (LV) end-diastolic pressure of 25 +/- 2 mm Hg was achieved. Embolization shortened the QT interval by 30 +/- 11 msec, while 1 and 2 mg/kg d-sotalol intravenously after embolization lengthened the QT interval by 23 +/- 7 and 39 +/- 7 msec, respectively (n = 7). Heart rate increased after embolization by 19 +/- 7 beats/min, while it decreased by 12 +/- 6 beats/min and by 21 +/- 5 beats/min after d-sotalol. The depressed LV function after embolization assessed by LV pressures, stroke volume, cardiac output, ultrasonometrically estimated LV volume, the pressure-volume relationship, and the time for isovolumic relaxation was not changed following infusion of 1 or 2 mg/kg d-sotalol. Plasma concentrations of d-sotalol were 1.55 +/- 0.33 and 2.58 +/- 0.50 micrograms/ml, respectively. In conclusion, d-sotalol at concentrations prolonging repolarization was devoid of cardiodepressive effects in acute ischemic heart failure in dogs.

Acute Disease↗
PubMed1992

Class III antiarrhythmic action and inotropy: effects of dofetilide in acute ischemic heart failure in dogs.

We studied the hemodynamic and metabolic effects of the novel class III antiarrhythmic agent dofetilide (UK-68,798) in acute ischemic heart failure. In pentobarbital-anesthetized dogs, heart failure was induced by microembolization of the area supplied by the main left coronary artery until a stable left ventricular (LV) end-diastolic pressure of 27 +/- 2 mm Hg was achieved. Embolization depressed LV systolic pressure, LV dP/dtmax, LV dP/dtmin, and cardiac output. None of these parameters were changed following i.v. infusion of dofetilide 5, 10, or 25 micrograms/kg, during spontaneous and paced cycle length of 300 ms (n = 9). Heart rate decreased by 12 +/- 8, 19 +/- 7, and 21 +/- 7 beats/min (p less than 0.05), while QT time increased by 23 +/- 7, 33 +/- 9, and 40 +/- 10 ms (p less than 0.05) after 5, 10, and 25 micrograms/kg, respectively. Ventricular effective refractory period increased from 128 +/- 10 to 153 +/- 11 ms after 25 micrograms/kg (n = 4). Arterial concentration and net myocardial uptake of glucose, lactate, and free fatty acids were not significantly influenced by dofetilide. In conclusion, dofetilide, at doses that prolonged repolarization, was devoid of cardiodepressive effects in acute ischemic heart failure.

Animals↗
PubMed1992

Class III antiarrhythmic action and inotropy: effects of almokalant in acute ischaemic heart failure in dogs.

We studied the haemodynamic and metabolic effects of the novel class III antiarrhythmic agent almokalant (H 234/09) in acute ischaemic heart failure at a dose prolonging ventricular repolarization. In pentobarbital anaesthetized dogs, heart failure was induced by microembolization of the area supplied by the main left coronary artery until a stable left ventricular end-diastolic pressure (LVEDP) of 32 +/- 2 mmHg was achieved. Embolization depressed LV dP/dt(max), LV dP/dt(min), left ventricular systolic pressure (LVSP) and cardiac output. After intravenous infusion of almokalant (0.35 micrograms/kg) LV dP/dt(max) and LV dP/dt(min) were not significantly changed at paced cycle length of 300 msec., whereas LVSP and aortic pressure decreased both at spontaneous and paced cycle length of 300 msec. LVEDP remained unchanged. Heart rate decreased from 185 +/- 7 to 167 +/- 5 beats/min., and corrected QT-time (QTc) increased from 9.5 +/- 0.3 to 10.4 +/- 0.5 msec. Arterial concentration and net myocardial uptake of glucose, lactate and free fatty acids were not significantly influenced by almokalant. In conclusion, almokalant at a dose prolonging ventricular repolarization had no negative inotropic effect in acute ischaemic heart failure.

Acute Disease↗
PubMed1992

The effect of the temperature of contrast media on cardiac electrophysiology and hemodynamics during coronary arteriography.

RATIONALE AND OBJECTIVES: The authors assess the effect of preheating ionic and nonionic contrast media on regional electrophysiologic and/or hemodynamic side effects during coronary arteriography. METHODS: The authors injected 6 mL of nonionic (iohexol) and ionic (ioxaglate) low-osmolality contrast media and NaCl 0.9% twice, at 20 degrees C and 37 degrees C, into the left coronary artery in eight open-chest dogs. To study regional electrophysiologic effects, the authors measured monophasic action potential duration (MAPD) using an epicardial suction electrode placed in the contrast-perfused area. Hemodynamic effects were studied by recording left ventricular systolic pressure (LVSP), mean aortic pressure, LV end diastolic pressure (LVEDP), LV dP/dtmax, and cardiac output. RESULTS: Ioxaglate and iohexol prolonged MAPD more at 20 degrees C than at 37 degrees C. NaCl 0.9% prolonged MAPD only when injected at 20 degrees C. The temperature of iohexol did not significantly influence LV pressures (LVPs) or LV dP/dtmax. Ioxaglate increased LVEDP and decreased LV dP/dtmax more at 20 degrees C than at 37 degrees C 10 seconds after injection. CONCLUSIONS: In dogs, contrast media, preheated to body temperature before selective injection during coronary arteriography, reduced dispersion of repolarization and reduced the risk of serious cardiovascular complications.

Action Potentials↗