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Biomedical subjects

D Fagret

Publications and source records attributed to D Fagret.

53 records · Page 3Linked to original sources
PubMed1991

Changes in left ventricular ejection fraction during REM sleep and exercise in chronic obstructive pulmonary disease and sleep apnoea syndrome.

Nine patients, 4 with chronic obstructive pulmonary disease (COPD) and 5 with obstructive sleep apnoea syndrome (OSAS) were monitored during sleep, rest and exercise. Left ventricular ejection fraction (LVEF) was investigated using gated equilibrium 99mtechnetium ventricular scintigraphy during rapid eye movement (REM) sleep, during exercise, and during wakeful rest. Control wakeful rest periods used for comparison with a study state (either REM sleep or exercise) were always selected during the same circadian segment as that state. Myocardial stress thallium-201 scintigraphy was performed during, and 4 h after, exercise, and results were compared to a daytime rest period. Several patients had myocardial hypoperfusion despite a normal electrocardiographic (ECG) treadmill test. During REM sleep, all patients exhibited a significant change in LVEF (greater than 5%) compared to wakefulness. During exercise, 5 subjects increased their LVEF normally (greater than 5%) and 4 (1 COPD, 3 OSAS) decreased it. All patients had a similar change (increase or decrease) during REM and at maximal exercise. Our results suggest that REM sleep in COPD and in OSAS can produce a myocardial stress as great as that produced by exercise. We conclude that REM sleep, like exercise, is a state in which morbidity may become higher and that it may account for mortality in COPD and OSAS patients with compromised myocardial circulation.

Adult↗
PubMed1990

Effect of glucose on the distribution of iodine-123-IHA-16 between esterification and oxidation in canine myocardium.

To evaluate the effect of glucose perfusion on the myocardial metabolism of [123I]-16-iodo-9-hexadecenoic acid (IHA), the latter was injected intravenously into six fasting dogs perfused with a solution lacking glucose (controls) and seven fasting dogs perfused with glucose and insulin. The distribution of myocardial 123I among iodides, free IHA, and esterified IHA was measured in myocardial biopsy specimens. The increase in esterification and decrease in oxidation of IHA due to glucose were quantified using a compartmental mathematical model of myocardial IHA metabolism. Subsequently, in six control and six glucose-perfused dogs, cardiac radioactivity was measured with a scintillation camera for 1 hr following i.v. injection of IHA. Four different methods were used to analyze the myocardial time-activity curves and to calculate the distribution of IHA between oxidation and esterification. Results comparable to those provided by analysis of biopsy specimens can be obtained by considering the curve to be the sum of an exponential and a constant, or by analyzing it with a compartmental mathematical model.

Animals↗
PubMed1989

Myocardial uptake of meta-[123I]-iodobenzylguanidine [( 123I]-MIBG) in patients with myocardial infarct.

Meta-123I-iodobenzylguanidine (123I-MIBG), which is an analog of norepinephrine, can be used to evaluate the integrity and function of sympathetic nerve endings in the heart. Myocardial uptake of 123I-MIBG was studied in 30 myocardial infarction patients and compared with the distribution of blood flow assessed with 201Tl. It was found that when a cold defect appeared on the 201Tl scintigram, its localization was identical to the cold defect on the 123I-MIBG scintigram. On the other hand, in three cases, a defect was found on the 123I-MIBG scintigram, corresponding to the electrocardiographic localization of the infarct, whereas the 201Tl scintigram was normal. Most strikingly, the present study shows that drugs (antagonists of the adrenergic receptors, calcium antagonists, amiodarone) decrease or even abolish (as in the case of labetalol) myocardial uptake of 123I-MIBG. Consequently, any interpretation of the 123I-MIBG scintigram must take into account the treatment administered.

3-Iodobenzylguanidine↗
PubMed1988

Iodomethylated fatty acid metabolism in mice and dogs.

The myocardial uptake of fatty acids labeled with radioactive iodine and injected i.v. can only be evaluated with SPECT if their oxidation kinetics is slow enough. For this reason, we evaluated different iodomethylated fatty acids in mice and dogs to determine which of them shows the highest myocardial uptake and the slowest oxidation. The most suitable was found to be 16-iodo-3-methyl hexadecanoic acid (mono beta) since its myocardial fixation was the same as that of the reference, i.e. 16-iodo-9-hexadecenoic acid (IHA), whereas it was degraded more slowly. Thirty min after injection of mono beta into dogs, the decrease in myocardial activity with respect to the maximum was two fold less than after IHA injection. The myocardial uptake of the two dimethylated fatty acids studied, i.e. 16-iodo-2,2-methyl hexadecanoic acid and 16-iodo-3,3-methyl hexadecanoic acid, was less than that of IHA in mice and dogs. In the latter, the myocardial uptake was so small that we were unable to study the time course of its activity. Consequently, these dimethylated fatty acids are not suitable for the study of the myocardial uptake of fatty acids in man.

Animals↗
PubMed1988

Value of myocardial defect size measured by thallium-201 SPECT: results of a multicenter trial comparing heparin and a new fibrinolytic agent.

In a multicenter randomized double-blind trial comparing heparin and a new fibrinolytic agent, anisoylated plasminogen streptokinase activator complex (APSAC), 231 patients presenting with a less than 5 hr acute myocardial infarction underwent a contrast angiography (CA) before the end of the first week of admission, and radionuclide cardiac blood-pool imaging and a 201Tl single photon emission computed tomography (SPECT) study before the end of the third week. Left ventricular ejection fraction (LVEF) and a wall motion score (WM) were calculated from CA. LVEF was also obtained from cardiac blood-pool imaging, and defect size (DS) from 201Tl SPECT. Results demonstrated that all parameters were significantly improved in patients treated with APSAC versus heparin (contrast LVEF 53 +/- 13 vs. 47 +/- 14 p less than 0.01, WM 9.8 +/- 6.5 vs. 13.3 +/- 7.9 p less than 0.001, radionuclide LVEF 43 +/- 12 vs. 40 +/- 13 p less than 0.05, DS 14 +/- 12 vs. 18 +/- 14 p less than 0.05). When the patients were divided according to infarct site and infarct-related coronary artery patency, it was demonstrated with all four parameters that the beneficial effect of APSAC can be largely explained by the lower incidence of vessel obstruction in this group (37% vs. 77% in the heparin group, p less than 0.001). It is concluded that (a) when compared with heparin and in the conditions of the trial, APSAC significantly improves the cardiac function and decreases the DS and (b) DS measured by 201Tl SPECT is as valuable a quantitative parameter of therapeutic evaluation as are LVEF and WM.

Anistreplase↗
PubMed1985

Kinetics of (16 123I) iodohexadecenoic acid metabolism in the rat myocardium, influence of glucose concentration in the perfusate and comparison with (1 14C) palmitate.

External counting, intracellular and subcellular distribution of (16 123I) iodohexadecenoic acid are studied on isolated rat hearts perfused with or without glucose. The presence of an exogenous substrate reduces the fatty acid oxidation and induces an increase of total cardiac and organic fraction activities. In this fraction, activity is very low for free fatty acids, but high for triglycerides and especially for polar lipids. The presence of an exogenous substrate leads to a more active esterification of fatty acids. Coronary effluents analysis shows, in the hydrophilic phase, a lower activity rebound in the presence of glucose. In the mitochondrial fraction, activity is mostly in the organic phase, as polar lipids especially. In the non-mitochondrial fraction, activity is much higher in the aqueous phase. 90 s p.i. of (l 14C) palmitic acid, over 80% of the myocardial activity is found in the hydrophilic fraction, which indicates--as for the iodo fatty acid (IHA)--an immediate and important oxidation, especially without glucose. These data seem to prove that IHA is taken up by the myocardial cells, enters the mitochondria where it is, without an early deiodination, oxidized with iodide release. IHA metabolic changes can be seen on the external detection myocardial activity curve. Omega iodinated fatty acids do not undergo a nonspecific important deiodination and are therefore well adapted to an external study of myocardial metabolism.

Animals↗
PubMed1985

[Prospective study of the value of echocardiography and myocardial scintigraphy with Tc 99m pyrophosphate during the acute stage of right ventricular infarction].

The aim of this study was to compare the clinical values of 99mTc pyrophosphate scintigraphy and M mode and 2D echography in the diagnosis of right ventricular infarction and in the predicting of some of its complications. Fifty-two patients were prospectively studied by echocardiography and scintigraphy at the acute stage of inferior wall infarction. Scintigraphy was performed in the antero-posterior and 45 degrees left anterior oblique incidences during the first 3 days of infarction. Right ventricular infarction was diagnosed if the right ventricular fixation was separated from the left ventricle by fixation at the base of the septum. Echocardiography was performed at an early stage by the usual 3 incidence. Dilatation of the right ventricle on the parasternal and submitral incidences; abnormal right ventricular contraction was searched for in all the incidences. The following results were obtained: scintigraphy showed a localised fixation allowing a topographic study in 40/52 patients (77%); satisfactory echocardiographic studies were obtained in 46/52 patients (88.5%). Signs of right ventricular infarction: scintigraphy showed signs of necrosis of the right ventricle in 12/40 patients (30%) who had a localised fixation; echocardiography showed dilatation (greater than 25 mm) of the superior part of the right ventricle with a right/left ventricle ratio greater than 0.5 in 16/46 patients (37%) with interpretable studies and obvious abnormalities of right ventricular wall motion in 7 patients (15.2%), less obvious in 10 other patients (22%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1985

Kinetics of iodomethylated hexadecanoic acid metabolism in the rat myocardium: influence of the number and the position of methyl radicals.

The methyl-branched fatty acids, if radioiodine labelled in alpha position, are potentially adapted to a selective study of FA myocardial uptake. To determine the position and the number of methyl radicals that are necessary to obtain a maximal uptake and a minimal degradation, we measured time-activity evolution of isolated and perfused rat hearts after an injection of iodinated fatty acids which are mono- or dimethylated in alpha or beta position. Except for dimethyl fatty acid, the uptake is similar for all fatty acids studied to that of the straight chain analogue; beta mono- or dimethyl fatty acids seem best adapted to a study of the uptake because alpha monomethyl fatty acids undergo a metabolic degradation and alpha mono- and dimethyl fatty acids induce ventricular fibrillations.

Animals↗
PubMed1985

[Cost/efficacy ratio in the diagnosis of coronary disease. Bayes' analysis by computer: respective role of the exercise test, isotopic methods and coronarography].

UNLABELLED: Between January 1983 and May 1984, 104 patients with no known cardiac pathology were referred by their cardiologist for diagnosis of chest pain. They all underwent coronary angiography which was used as the reference investigation and the following sequential Bayes' analysis was performed. The percentage probability of coronary artery disease was estimated from clinical date (age, sex, characteristics of the chest pain subdivided into 3 groups); an exercise ECG was performed in all cases (classified as positive, negative or non diagnostic); if the probability of coronary artery disease was greater than 95% (or less than 5%) after exercise stress testing the patients was diagnosed as having (or not having) coronary artery disease. If the probability was between 6 and 94% the patient underwent Thallium myocardial scintigraphy (Thallium dipyridamole; analysis on a colour television screen); the coronary risk probability before Thallium was that calculated after exercise stress testing. If after myocardial scintigraphy the coronary risk remained between 6 and 94%, an exercise angioscintigraphy was performed and interpreted in the same way. The clinical and complementary date was analysed on a mini-computer, the values of the sensitivity and specificity of the tests used for the calculation of the probability of coronary artery disease were those previously published by our group. RESULTS: 31/88 (35%) of patients were classified in the 5% risk groups after exercise stress testing (24 coronary artery disease; 7 normals: no errors of classification). Fifty six out of the 88 patients (65%) were classified in the 5% risk group after myocardial scintigraphy (42 patients with coronary artery disease with 41 abnormal coronary angiographies and 14 normal patients, all of whom had normal coronary angiographies; this represents a 1.8% divergence of classification compared with coronary angiography). Angioscintigraphy only classified 3 of the remaining patients, one wrongly, and did not seem to be useful diagnostically as a third-line investigation after Thallium scintigraphy or as a second-line investigation instead of Thallium scintigraphy. This strategy is less costly than carrying out coronary angiography systematically in these patients: if diagnostic coronary angiography is performed alone in patients with a risk of 6 to 94% the cost is 4 800 FF vs 10 400 FF per patient; if coronary angiography is performed in all patients in whom coronary artery disease is possible or certain (all patients with a risk of over 5%), the cost is 8 400 FF vs 10 400 FF per patient, a saving of 20%.(ABSTRACT TRUNCATED AT 400 WORDS)

Bayes Theorem↗
PubMedDate not supplied

Assessment of insulin sensitivity in vivo in control and diabetic mice with a radioactive tracer of glucose transport: [125I]-6-deoxy-6-iodo-D-glucose.

BACKGROUND: Impairment of insulin-stimulated glucose transport is a characteristic of type 2 diabetes. A radioactive glucose analogue has been synthesized: [(125)I]-6-deoxy-6-iodo-D-glucose. Its biological behaviour in vitro is similar to that of 3-O-methyl-D-glucose, the reference tracer of glucose transport. The aim of the present study was to determine the ability of [(125)I]-6-deoxy-6-iodo-D-glucose to evaluate variations in glucose transport in vivo. METHODS: Biodistributions of [(125)I]-6-deoxy-6-iodo-D-glucose were performed with or without exogenous insulin (iv injection of 1.5 IU/kg) in db/+ non-diabetic control mice and in db/db type 2 diabetic mice, exhibiting a severe insulin resistance characterized by a lack of increase in glucose uptake in response to insulin. RESULTS: In db/+ mice, insulin increased [(125)I]-6-deoxy-6-iodo-D-glucose transport by 30% in most insulin-sensitive tissues (heart, diaphragm and skeletal muscle, p < 0.05) and had no effect in other organs. In db/db mice, [(125)I]-6-deoxy-6-iodo-D-glucose transport in these organs was not modified by insulin. CONCLUSION: [(125)I]-6-deoxy-6-iodo-D-glucose is able to trace in vivo an increase in glucose transport with insulin in non-diabetic mice and a defect of glucose transport in type 2 diabetic mice. It is the first time that an iodinated analogue of glucose has shown such promising results after in vivo injection. The use of this tracer to assess glucose transport in vivo in humans via nuclear imaging warrants further investigation.

Animals↗
PubMedDate not supplied

Synthesis and biological evaluation of new diisocyanide- and triisocyanide-99mTc complexes.

This paper describes the synthesis of four new polyisocyanides (three diisocyanides and one triisocyanide). The complexation of 99mTc with these ligands is also studied through chromatography and revealed the formation of hexacoordinated 99mTc+1 complexes. Finally, biodistributions of these complexes in mice are given and compared. Heart captations are lower than the ones with [99mTc(MIBI)6]+ but remain constant and a satisfactory lungs clearance, probably due to the metabolization of the ligands, is observed.

Animals↗
PubMedDate not supplied

Influence of calcium channel inhibitors on the myocardial uptake and retention of technetium 99m N-NOET, a new myocardial perfusion imaging agent: a study on isolated perfused rat hearts.

BACKGROUND: Technetium 99m N-NOET is a new myocardial perfusion imaging agent currently in phase III clinical trials in Europe. In vitro studies on newborn rat cardiomyocytes have shown that calcium inhibitors, such as verapamil or diltiazem, inhibit its cellular uptake by 40%. To determine whether such a specificity exists ex vivo, we studied the effect of verapamil, diltiazem, and nifedipine on the myocardial uptake and retention of Tc-99m N-NOET in isolated perfused rat hearts. METHODS AND RESULTS: After a 15-minute baseline period, rat hearts were perfused with 0.5 micromol/L verapamil (n = 6), 0.75 micromol/L diltiazem (n = 6), or 0.1 micromol/L nifedipine (n = 6) for 10 minutes before the injection of a bolus (40 microCi/250 microL) of the tracer. Control hearts were perfused with either 1.5 mmol/L calcium (same concentration as in the treated groups; n = 7) or 0.75 mmol/L calcium (same contractility as in the treated groups; n = 6). Myocardial activity of Tc-99m N-NOET was monitored for 30 minutes. The functional parameters of the hearts were recorded throughout the experiments. Calcium inhibitors induced a 40% to 55% decrease in maximal first derivative of left ventricular pressure (dP/dt) (0.0001<P< .001 versus control, calcium 1.5 mmol/L). After 30 minutes, tracer retention was 51.6%+/-6.1% injected dose (ID)/g and 54.2%+/-10.2% ID/g for control hearts perfused with 1.5 mmol/L and 0.75 mmol/L calcium, respectively (P = not significant). Myocardial activity of Tc-99m N-NOET was not modified in hearts perfused with verapamil (50.0%+/-4.1% ID/g), diltiazem (47.2%+/-8.7% ID/g), or nifedipine (51.7%+/-3.4% ID/g; P = not significant versus control hearts perfused with 1.5 mmol/L or 0.75 mmol/L calcium). CONCLUSIONS: Verapamil, diltiazem, and nifedipine were not responsible for any variations in Tc-99m N-NOET uptake and retention in the isolated rat-heart model. This might be explained by the binding of the tracer to endothelial cells, which do not present voltage-dependent calcium channels.

Animals↗
PubMedDate not supplied

Potential use of radiolabeled antisense oligonucleotides in oncology.

Antisense oligodeoxynucleotides (ODNs) have great promise for therapy. Oligomers labeled with gamma-emitting radioelements have great promise for diagnosis. These radiolabeled oligomers can be used to identify the presence of a particular messenger RNA through simple external detection of radioactivity by means of scintigraphy. This review evaluates the progress in the development of antisense oligodeoxynucleotides for non-invasive imaging of chemoresistance. As nominated by H.N. Wagner at the final session of Nuclear Medicine congress in Denver, the deoxyribonucleic acid is "the molecule of the millennium".

Humans↗
PubMedDate not supplied

Detection of chemoresistance profile of cell lines K562, KB, GLC4 and HL60 through characterisation of the hmdr1, mrp and lrp transcripts.

The current trend in innovative cancer therapy is moving towards targeting the genes of interest by means of oligonucleotides developed for therapeutic or diagnostic use. These new approaches are of particular interest in oncology, and it would therefore be extremely useful to characterise all the biological tools currently available in this field. The chemoresistance profiles of four human cancer cell lines were determined by identifying of the operating conditions needed to characterise the presence of hmdr1, mrp and lrp mRNA by gene amplification.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Measurement of right ventricular ejection fraction with krypton-81m in chronic obstructive pulmonary disease.

Thirty patients with chronic obstructive pulmonary disease (COPD) and 15 healthy volunteers have been studied to assess the value of measuring right ventricular ejection fraction (RVEF) at rest with a perfusion of krypton-81m (81mKr). With this perfusion, equilibrium RVEF can be measured in a 30 degrees right anterior oblique projection, avoiding a superimposition of cardiac cavities. The average RVEF of the patients with COPD was significantly lower than that of the normal patients (36.3 +/- 9.3% vs 52.6 +/- 3.9%; p less than 0.001). An inverse linear relation was found between mean pulmonary artery pressure (Ppa) and RVEF (r = -0.543; p less than 0.01). The RVEF in a group of 15 patients with COPD and pulmonary hypertension (Ppa greater than 20 mmHg), averaged 30.4 +/- 7.26%, which was significantly lower than that of the other 15 COPD patients with normal Ppa, whose RVEF averaged 42.3 +/- 7.1% (p less than 0.01). Taking a RVEF value less than or equal to 35% as an indicator of pulmonary hypertension, the sensitivity was 80% and specificity was 75%, the predictive value for a positive test was 75%, and for a negative test was 80%. A positive but weak correlation was found between RVEF and PaO2 (r = 0.52; p less than 0.01), SaO2 (r = 0.41; p less than 0.05) and the forced expiratory volume in one second (FEV1) (r = 0.40; p less than 0.05). No correlation was found between RVEF and prior history of right cardiac insufficiency, PaCO2, pH, the ratio FEV1/vital capacity, ECG signs of cor pulmonale and left ventricular ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗