Biomedical subjects

M Comet

Publications and source records attributed to M Comet.

At least 19 recordsLinked to original sources

PubMed1992

Assessment of iodohexadecenoic acid as a tracer of fatty acid metabolism by external detection: a study on isolated rat heart.

Labelled fatty acids have been proposed to explore cardiac metabolism. For the analysis of the external detection curve obtained with 16-iodo 9-hexadecenoic acid (IHA), we developed a mathematical 4-compartment model with compartments 0, 1, 2 and 3 representing vascular IHA, intracellular IHA, esterified forms and iodide, respectively. This model, used here for isolated rat hearts perfused in a recirculating system, is validated by an intracellular analysis, then tested in various metabolic conditions. Thus, the mathematical analysis of the external detection curve gives us numerical data on IHA metabolism, especially the distribution between degradation and storage. Our results confirm the suitability of IHA for assessing myocardial metabolism.

Animals↗

PubMed1992

[Value of new isotopes in cardiology].

Nuclear Cardiology has seen many advances in the past few years: new indications for tracers already known, but also the appearance of new markers, by single photon imaging or by position emission (PET). With regard to the investigation of myocardial perfusion, thallium remains the most widely used isotope. Its sensitivity in the diagnosis of coronary disease is improved by the use of scintigraphic CT scan (SPECT) and excellent predictive value in terms of the onset of coronary events or mortality has been confirmed in particular. At the same time, the sensitivity and specificity of new technetium markers have been better defined. The investigation of myocardial metabolism, accessible up to now only via PET and confined, in France, to the domain of clinical research, is in the process of becoming a tool suitable for use by clinicians as a result of new SPECT-Thallium protocols (reinjection, late redistribution and rest), but also because of the development of single photon markers of myocardial viability, e.g. iodinated fatty acids. A functional approach to coronary disease, indispensable adjuvant to the anatomical approach, is now possible on a routine basis.

Heart Diseases↗

PubMed1992

Comparative effects of halothane associated with verapamil and ischaemia on myocardial metabolism in isolated perfused rat hearts.

The association of verapamil with halothane causes ischaemic-like myocardial dysfunction. Using an isolated rat heart model perfused with a radiolabelled fatty acid (123I-labelled iodohexadecenoic acid) as a sensitive marker of ischaemia this study investigated whether or not this dysfunction is of ischaemic origin. Hearts were perfused with a control solution or with solutions containing either 1% of halothane or 150 ng ml-1 of verapamil or the association of 0.75% halothane + 120 ng ml-1 verapamil. The ischaemic group was perfused at a reduced perfusion rate (-50%). Intracellular fate of IHA was assessed, and its esterification ratio computed. Ischaemia and the drugs induced a similar depression of haemodynamics. The esterification ratio in the ischaemic group was significantly higher (0.723 +/- 0.04) than in controls (0.0526 +/- 0.03) and than in the treated groups: halothane (0.533 +/- 0.06), verapamil (0.411 +/- 0.027) or the association halothane+verapamil (0.408 +/- 0.05), suggesting a non-ischaemic origin for the dysfunction caused by halothane-verapamil.

Animals↗

PubMed1992

[Comparison of different methods for serum folate assay].

Folates were determined in 148 patient sera, using four different methods: a microbiological assay (Reference Method), two radioassays (Magic B12 FOL [NB] and SimulTRAC SNB no boil kits) and a non isotopic competition method (Magic Lite kit). Folate mean varied according to the methods 10.0 nmol.l-1 (reference method), 12.2 nmol.l-1 (Magic Lite), 8.7 nmol.l-1 (Magic B12 FOL [NB]) and 10.8 nmol.l-1 (SimulTRAC SNB NO boil). Poor correlations were also noted (0.83 < r < 0.95, figures 1 and 2). Differences between methods were explained according to the literature.

Bacteriological Techniques↗

PubMed1991

Evaluation of cellular viability by quantitative autoradiographic study of myocardial uptake of a fatty acid analogue in isoproterenol-induced focal rat heart necrosis.

Previous studies led us to hypothesize that a fatty acid analogue, 15-p-iodophenyl-beta-methyl pentadecanoic acid (IMPPA or BMIPP), which is taken up but not quickly metabolized by heart cells, would be a more suitable tracer of cellular viability than thallium-201. Biodistribution studies of 1-14C-IMPPA in conscious, freely moving rats showed that the concentration ratio of radioactivity in the heart with respect to the blood was about 8 for at least 60 min after intravenous administration, permitting its use as a putative tracer in these conscious, freely moving rats. Thereafter, the myocardial uptake of 14C-IMPPA was studied in isoproterenol-treated rats (daily treatment for 10 days in order to induce cardiac hypertrophy and necrotic foci) with respect to control ones. Comparison of myocardial localizations by quantitative autoradiography of the uptake of 201Tl and 14C-IMPPA with that of triphenyltetrazolium chloride (TTC) staining enabled comparative evaluation of nutritional blood flow, localization and uptake of 14C-IMPPA and necrotic foci size. Distributions of 14C-IMPPA and 201Tl in control rats' hearts were homogeneous, like TTC staining. In infarcted hearts, areas of decreased 14C-IMPPA uptake were nearly the same (100% +/- 5%) as those unstained by TTC. These areas were larger than those showing a decrease in thallium uptake (about 70% +/- 5% of the total scar size). Therefore, IMPPA seems to be a more accurate and sensitive indicator of necrosis localization compared with thallium. It may be a useful agent for assessment of myocardial viability by single photon emission tomography (SPET) imaging.

Animals↗

PubMed1991

[Evaluation of a DNA probe test for the detection of Legionella SPP].

Seventeen suspension of Legionella pneumophila and ten of Legionella bozemanii in saline or bronchoalveolar lavage (BAL) fluid were tested using the Gen Probe technique. The detection threshold was found to be 10(3)-10(4) CFU/ml. Specificity and sensitivity were evaluated by using the probe on 8 suspensions of bacteria other than Legionella and by performing a comparative study of the probe test, direct immunofluorescence and culture with 103 specimens (BAL fluid in most instances) from 92 patients with possible legionellosis. Sensitivity was found to be acceptable (3 of the 4 culture-positive specimens were positive by the probe test) and specificity was 100% despite the fact that most (80/99) BAL specimens were not sterile and regardless of the cutoff level used to define positivity. The advantages of the DNA probe test, including rapidity, simplicity and objectivity, should be weighed against its disadvantage, i.e., only acceptable sensitivity and use of radioactivity.

DNA Probes↗

PubMed1990

The intramyocardial fate of [1-14C] palmitate, iodopalmitate and iodophenylpentadecanoate in isolated rat hearts. A contribution to the choice of an iodinated fatty acid as a tracer of myocardial metabolism.

Labeled iodinated fatty acids (FAs) have been proposed to explore myocardial metabolism by external detection in man. We have chosen a 16-carbon FA, iodinated in omega position, whereas other authors use an iodophenylated FA. To explore the influence of the presence of an iodine or of an iodophenyl radical on the metabolism of the FA, we have compared, in isolated rat hearts perfused in a recirculating system, the intramyocardial fate of palmitate (PA), iodopalmitate (IPA), and iodophenylpentadecanoate (IPPA), the 3 of them being labeled with C14 in position 1. The addition of the iodine atom brings about a hindrance to the esterification of the FA into triglycerides, but not modification of the myocardial uptake and of the CO2 produced. The addition of the iodophenyl radical impairs both the FA storage and its oxidation, leading to a very high level of free FA. The phospholipid distribution is also modified. Apart from their myocardial use in the isolated rat heart, the 3 FAs were assayed in vitro as a substrate for acylCoA-synthase. As IPA more closely mimics native FA metabolism, it is therefore more suitable than IPPA as a tracer of myocardial metabolism.

Animals↗

PubMed1990

Influence of the presence of a methyl group on the myocardial metabolism of 15-(paraiodophenyl)-3 methyl pentadecanoic acid (IMPPA).

The objective of the present study was to determine the mechanism of accumulation of myocardial activity following i.v. injection of 15-(paraiodophenyl)-3 methyl pentadecanoic acid (IMPPA). IMPPA and 15 phenyl-3 methyl pentadecanoic acid (MPPA) were labeled with 14C at position 1 and used to perfuse isolated rat hearts in a closed system. After 5 min of perfusion, IMPPA reached 2/3 of its value at 45 min. 14CO2 production was low. Most of the myocardial activity was in the form of free IMPPA. Analysis of IMPPA activation by CoA SH revealed that it was very strongly inhibited. The retention of myocardial activity is thus due to intracellular accumulation of free IMPPA following inhibition of activation. Comparison of results obtained with IMPPA and MPPA showed that the presence of iodine in the molecule accentuates the inhibition of activation.

Animals↗

PubMed1990

Effect of short-term fasting on [123I] iodohexadecenoic acid metabolism in the isolated perfused rat heart. Validation of mathematical model by comparison with experimental measurements.

In order to study metabolic modifications induced by short term fasting and their consequences on the uptake and intracellular fate of fatty acids iodine labelled in omega position, rats undergo a 36h fasting. Hearts are perfused in a Langendorff system with a glucose (11 mM) perfusion medium; [123I] hexadecenoic acid (IHA) is injected as a bolus. A comparison between time-activity curves p.i. demonstrates a much faster activity decrease for the hearts fasted animals. The intracellular analysis shows that short fasting did not significantly increase the myocardial uptake of fatty acids, but decreased the storage and increased the degradation of the fatty acids taken up. Mathematical analysis of the myocardial time-activity curves obtained by external detection provided results comparable to those of intracellular analysis. The coefficients of correlation between the values of the aqueous phases, organic phases and free fatty acids measured by intracellular analysis and calculated with the compartmental model are consistently higher than 0.97. Consequently, this experimental model combined with mathematical analysis of the time-course of myocardial radioactivity after 123IHA administration appears to be very promising method for studying the effects of drugs or variations of energy substrate availability on myocardial fatty-acid metabolism.

Animals↗

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↗

PubMed1989

Does medical treatment of lymphedema act by increasing lymph flow?

The lymphatic origin of chronic edema of the lower limbs was identified by lymphoscintigraphic exploration. Patients underwent therapy involving 8 days of manual lymph drainage combined with elevation of the limbs during rest periods and double compression bandaging. Manual drainage increased lymph flow in 16 limbs, implying that the edema resulted from a functional lymphatic anomaly. In contrast, manual drainage did not increase lymph flow in 9 limbs, suggesting a structural anomaly of the lymphatics. Hence, the same clinical picture corresponded to two different lymphatic anomalies, distinguished by lymphoscintigraphy. However, the therapeutic results were independent of the lymphoscintigraphic results. Increased lymph flow is therefore not the only explanation for the decrease in edema during therapy.

Adolescent↗

PubMed1989

[Theoretical and practical problems posed by the measurement of capillary filtration by radioactive tracers].

Screening for abnormal capillary filtration in the limbs with radioactive tracers requires the use of molecules of a known hydrodynamic radius. The molecule labeling should be obtained with a pure gamma-emitting radioactive atom, presenting a steady bond with the molecule, in vivo. Indium-111-labeled albumin appears to be the best tracer, and should be injected concurrently with the technetium 99m-labeled erythrocytes. The latter tracer permits assessing volume variations induced by the venous blood return block needed to obtain a capillary pressure increase. A qualitative estimation of lymphatic flow, and screening for abnormal permeability of the lymphatic vessels must be carried out as part of any capillary filtration study protocol.

Capillary Permeability↗

PubMed1989

[Emergency treatment in decompression accidents in shipyards].

The Comex company has underwater workplaces scattered over the whole world, which are therefore very often far away from a medical center equipped for the treatment of decompression sickness. However, the subsequent evolution of such an event depends mainly on how fast the first aid is given to the patient. Therefore, the scientific and medical departments of our company developed a medical handbook to be used by chiefs of working platforms. The text which has to be easily understandable, mentions: a cursory description of the clinical signs of the different decompression accidents the measures which have to be taken in each case, depending on: the moment of the emergency: after or during decompression, the presence of an insufficient decompression, or a "blow-up". The handbook contains several recompression tables, first aid treatment recommendations and drugs. It has to be stressed that these procedures are only emergency steps. They should be performed before the patient can be transferred to a medical center with expertise in the treatment of decompression accidents.

Accidents↗

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↗

PubMed1988

Myocardial metabolism of radioiodinated methyl-branched fatty acids.

Methylated fatty acids labeled with radioactive iodine have been proposed as a means of studying regional myocardial uptake of fatty acids in man. To investigate the methylated fatty acid that is best adapted for an assessment of uptake, we have studied the influence of the number and the position of the methyl groups of IFA intracellular metabolism; 16-iodo-2-methyl-hexadecanoic (mono-alpha), 16-iodo-2,2-methyl hexadecanoic (di-alpha), 16-iodo-3-methyl-hexadecanoic (mono-beta), and 16-iodo-3,3-methyl-hexadecanoic (di-beta) acids were injected into the coronary arteries of isolated rat hearts. Intracellular analysis shows that the degradation of mono-alpha was always lower than that of IHA and the storage was always much higher. The differences between mono-beta and IHA were similar to those observed with mono-alpha, but were much more pronounced. With the two dimethylated IFAs there was an inhibition of both oxidation and esterification which led to an accumulation of free FAs in myocardial cells. In conclusion, mono-beta, di-alpha, and di-beta are potentially suitable for studying the cellular uptake of IFA since all of them, and particularly the dimethylated IFAs, have a low oxidation rate.

Animals↗

PubMed1987

A new experimental model for studies of drug actions on myocardial metabolism. Application to a study of the influence of POCA.

In order to study myocardial metabolism by external detection, quantitative information on the metabolism of a gamma-emitting iodinated fatty acid (IHA) was obtained from time-activity curves of radioactivity in different compartments. A 4-compartment mathematical model was then developed; compartments 0, 1, 2, and 3 correspond respectively to vascular IHA, intracellular IHA, esterified forms, and iodide resulting from mitochondrial oxidation of IHA. We applied this model to a study of the influence of an inhibitor of fatty acid oxidation, POCA (2-[5(4 chlorophenyl) pentyl]-oxirane-2-carboxylate). Isolated rat hearts were perfused for 20 min with Krebs liquid containing increasing concentrations of POCA. IHA was then injected as a bolus at the entrance of the coronary network. The level of cardiac radioactivity was recorded for 30 min and the division into the 4 compartments was simulated at different concentrations of POCA. The drug appeared to increase the myocardial retention of IHA and slow down the speed of degradation and storage; the variations were dose-dependent. These results correspond to those obtained by intracellular analysis. The proposed method, which is reliable and sensitive, is an interesting experiment for pharmacological studies of cardiac metabolism.

Animals↗