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Biomedical subjects

G Marchal

Publications and source records attributed to G Marchal.

At least 145 records · Page 8Linked to original sources
PubMed1996

Characterization of murine monoclonal antibodies specific for the 45/47 kDa antigen complex (APA) of Mycobacterium tuberculosis, M. bovis and BCG.

The alanine-proline antigen (APA), representing less than 2% of the released or excreted material during Mycobacterium tuberculosis or bacillus Calmette-Guérin (BCG) growth, is a dominant antigen present during M. tuberculosis infection or BCG immunization. To obtain new tools to dissect the major epitopes of the APA molecules, seven monoclonal antibodies (mAbs) against the purified molecules were developed. Epitope maps of the mAbs were obtained on APA molecules absorbed on plastic surfaces or in solution (BIAcore technology). The mAbs were found to be independent or to be different despite binding to adjacent or overlapping epitopes. In Western blot assays some proteins secreted in culture fluid by M. avium, M. kansasii, M. smegmatis or M. xenopi were also labelled by six of the seven antibodies. Conversely one antibody was specific for the proteins from the M. tuberculosis complex (I10-0,3) demonstrating that the APA molecules have some properties or general conformations that are specific for M. tuberculosis and M. bovis.

Animals↗
PubMed1996

Spontaneous neurological recovery after stroke and the fate of the ischemic penumbra.

We prospectively tested the hypothesis that early recovery after ischemic stroke depends on the ultimate survival of functionally impaired, critically ischemic (i.e., "penumbral") tissue. From a series of 26 consecutive patients studied with positron emission tomography within 18 hours of first-ever stroke in the middle cerebral artery territory, all 11 survivors to the 2-month end point who exhibited increased oxygen extraction fraction were declared eligible. The positron emission tomographic images were compared to ultimate infarction defined by computed tomography performed during the chronic stage. The penumbra (operationally defined by increased oxygen extraction fraction and divided outcome despite uniformly reduced cerebral blood flow) was individually detected in 10 of the 11 patients; cerebral blood flow ranged from 7 to 17 ml/100 gm x min, consistent with that found in monkey studies. The volume of the penumbra that escaped infarction was highly correlated with neurological recovery (p < 0.04 to p < 0.0001, depending on the scale used). This longitudinal study is the first to characterize the penumbra in humans and to document one mechanism strongly influencing recovery; the surviving penumbra may offer opportunities for secondary perifocal neuronal reorganization. Therapeutic measures to prevent infarction of the penumbra (up to 16 hours in this series) may have reduced residual neurological impairment. Mapping the extent of the penumbra, according to prospective criteria, may allow one to predict each patient's potential for recovery, and to select the most appropriate candidates for therapeutic trials.

Aged↗
PubMed1996

Detection and characterization of primary liver cancer in rats by MS-264-enhanced MRI.

A new MR contrast agent, MS-264 (Gd(1RS)-1-(p-butylbenzyl)-DTPA), was developed to achieve hepatobiliary specificity and its potential evaluated for detecting and characterizing liver tumors in rats with chemically induced hepatocellular carcinoma (HCC). In seven rats with 66 HCC lesions, enhancements of different abdominal organs and tumors were compared on T1-weighted images after intravenous administration of Gd-DTPA (0.3 mmol/kg) and MS-264 (0.05 mmol/kg). MR images were correlated with postmortem microangiographic and histological findings. An overall enhancement of different organs, which normalized within 24 h, was observed after Gd-DTPA and MS-264 injection. MS-264 caused a higher relative enhancement (RE) in liver (60%), compared with that of Gd-DTPA (40%), which resulted in a prompt negative contrast enhancement in 59 of 66 HCCs. All were moderately to poorly differentiated (Grades II-IV) tumors. Six of these 59 negative contrast-enhancing lesions showed a positively enhanced peritumoral rim, which corresponded histologically to malignant infiltration (n = 2) or compression (n = 4). On the other hand, six well differentiated HCCs showed prolonged positive enhancement. However, one well differentiated HCC was not positively enhanced by MS-264, probably due to poor access of the agent to the lesion. In comparison to that of the precontrast images, enhancement with Gd-DTPA and MS-264 increased the number of detected lesions by 22 and 42%, respectively. In this animal study, MS-264 proved to be useful in detection and characterization of primary liver cancers.

Animals↗
PubMed1996

Assessment of accuracy of renal artery stenosis grading in helical CT angiography using maximum intensity projections.

The purpose of the study was to investigate whether visual inspection of maximum intensity projection (MIP) images is a reliable method for assessment of the severity of renal artery stenoses (RAS). Therefore, 20 RAS were investigated with helical CT. Native axial images and MIP images were analysed separately or in combination ("two-step method"). A phantom study was performed to investigate the influence of window setting on apparent stenosis severity. Accuracy for diagnosis of 50-69% and 70-99% RAS and the mean inter-observer agreement were 82.5%, 77.5% and 82.5% respectively, using study of MIP images alone, and 100%, 97.5% and 95% using the "two-step method". The phantom study showed that the apparent severity of vascular stenoses on MIP images depends on the selected window centre values. It is concluded that combined evaluation of both MIP images and native axial images is more reliable than study of MIP images alone for assessing the severity of RAS.

Aged↗
PubMed1996

Paramagnetic metalloporphyrins: infarct avid contrast agents for diagnosis of acute myocardial infarction by MRI.

In previous experiments in tumors we demonstrated that metalloporphyrins are particularly avid for nonviable tumor components. This study was performed to find out whether these agents can be used as MRI contrast agents for the visualization of acute myocardial infarction (MI). A total of 44 rats, 6 normal controls and 38 with occlusive MI (2-24 h old), were used. Gadolinium mesoporphyrin (Gd-MP) or manganese tetraphenylporphyrin (Mn-TPP) was intravenously injected at doses of 0.1, 0.05, and 0.01 mmol/kg. Three to 24 h after injection, axial and coronal T1-weighted (TR/TE 300/15 ms) spin-echo MR images were obtained before and after killing the animals and correlated with triphenyl tetrazolium chloride (TTC) histochemical preparations. The Gd-MP content in infarcted and noninfarcted myocardium was measured using inductively coupled plasma atomic emission spectroscopy (ICP-AES). MRI without contrast media could not discern the MI. However, 3-24 h after injection of either Gd-MP or Mn-TPP, the infarcted area was positively stained on MR images. This area matched well with the negatively TTC-stained area on the heart slices (r = 0.97). The contrast ratios between the infarcted necrotic myocardium and the noninfarcted regions varied from 150 to 300% depending on the type of agents and doses used. Neither false-positive nor false-negative findings were encountered. The metalloporphyrin concentration was more than 10 times higher in the infarcted than in the noninfarcted heart. Metalloporphyrins appear to be promising MRI contrast agents for detection and quantification of necrosis in MI. These preclinical results may open new perspectives in cardiac imaging.

Animals↗
PubMed1996

Left ventricular radial tagging acquisition using gradient-recalled-echo techniques: sequence optimization.

Myocardial tagging with magnetic resonance (MR) imaging offers unique possibilities for noninvasive left ventricular (LV) strain analysis. True three-dimensional strain analysis can be achieved with tags implemented in cardiac short axis and long axis images. Spin-echo (SE) techniques have been used for these studies. However, this approach is time-consuming: images at different phases of the cardiac cycle have to be obtained in successive measurements and hence the total number of measurements equals the number of time frames. Moreover, the images are often degraded by flow and motion artifacts. The purpose of this study was to optimize a faster and more robust MR tagging sequence for use on a clinical whole-body 1 T MR system with optimal persistence of the tags during the entire cardiac cycle. The tagging pulses were implemented in gradient-recalled-echo (GRE) sequences and compared to SE-based acquisitions. The effects of the use of flow-compensating gradients, the excitation angles, and the angles of the saturation pulses have been studied with MR signal simulations and in comparative measurements in volunteers. GRE acquisitions with flow-compensating gradients are robust techniques for myocardial tagging acquisitions. Use of optimized flip angles and saturation pulses can significantly improve delineation of the tag and can be used up to at least 700 ms after the R-wave. Therefore, LV tagging with GRE acquisitions using optimized MR parameters is a robust and promising technique.

Heart↗
PubMed1996

Spiral CT of intracranial aneurysms: correlation with digital subtraction and magnetic resonance angiography.

Spiral CT and magnetic resonance angiography (MRA) were performed in ten patients with 14 intracranial aneurysms known from conventional angiography. All lesions, the smallest 3 mm in diameter, were visible on spiral CT and MRA. The neck of the aneurysm and its anatomical relations could very accurately be determined in all cases. Advantages of spiral CT over MRA are: a short acquisition time with reduction of motion artefacts, no dependence on flow rate or cardiac output, and excellent visualisation of calcification, thrombus and bony landmarks. Disadvantages are the necessity for iodinated contrast medium, long postprocessing and reconstruction time and the possibility of overlap of bone and venous blood.

Aged↗
PubMed1996

Contrast-enhanced MR angiography.

Despite many optimizations, the current limitations of plain MR angiography include: saturation that impairs the visualization of veins and arteries with slow flow and spin-dephasing signal voids in locations with turbulent flow. Recently, the use of contrast agents has been proposed to cope with these remaining problems. Because of induced shortening of the T1 of the blood, saturation in the blood vessels is overcome. As a result, arteries and veins are visualized with the same signal intensity, which makes the technique less flow-dependent. In combination with short T1-weighted acquisitions, today CE MRA can be obtained while the patient is holding his breath. This last approach is most promising for abdominal applications since the respiratory motion can be frozen. As these acquisitions also use very short echo times, spin dephasing can be reduced. In conclusion, the use of contrast agents has greatly increased the clinical usefulness of MR angiography.

Animals↗
PubMed1996

Integrating digital ICU viewing into the global working environment.

We illustrate that to benefit from the advantages of Picture Archiving and Communication Systems (PACS) for the Intensive Care Unit (ICU), the PACS must be strongly integrated within the overall working environment. This includes adaptation of the PACS toward specific working patterns and integrating it with the Hospital Information System (HIS). This is reflected in our prototype system in different ways. The user interface of the viewing station is centered around often used patterns in ICU viewing. Information about bed occupancy is retrieved from the HIS and exploited in the viewing station. A digital connection between the phosphorplate scanner and the HIS ensures that images are correctly related to other patient information and to previous images. Using minor adaptations to the existing HIS, PACS and HIS have been made to cooperate in integrated presentation of images and radiological reports, as a step towards a multi-media medical information system. We discuss the relation between PACS and the global information environment, emphasizing organizational issues rather than technological aspects.

Computer Systems↗
PubMed1996

Early spontaneous hyperperfusion after stroke. A marker of favourable tissue outcome?

To clarify the relationships between early hyperperfusion (i.e. the hallmark of early, efficient recanalization in animal stroke models) and ultimate infarction, we have compared acute-stage perfusion PET images and chronic-stage CT scans in patients with middle cerebral artery (MCA) stroke. We used PET and the oxygen-15 (15O) equilibrium method to obtain cerebral blood flow (CBF), cerebral blood volume (CBV), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO2) parametric images in 30 consecutive, still symptomatic, first-ever MCA territory stroke patients without sign of haemorrhage at admission CT scan. Each subject was studied twice, first within 5-18 h of stroke onset, and, in survivors, approximately 1 month later; a plain CT scan (co-registered with PET) was performed approximately 1 month after onset. Following initial screening based on acute-stage perfusion images, 10 survivors with focal hyperperfusion in the appropriate MCA territory confirmed by computer were declared eligible. In each patient, the topography and volume of both hyperperfusion and infarction (delineated on late CT scan) were recorded, and all PET parameters were obtained for both areas and both times. The hyperperfused areas affected the cortical MCA territory, often widely so and in a patchy fashion; they were topographically distinct from, and consistently larger than (P < 0.01, Wilcoxon sign test) the final infarcts, which were small and generally deep-seated. In none of the nine patients in whom it was successfully performed did transcranial Doppler reveal MCA stem occlusion. In the hyperperfused regions, the acute-stage perfusion, blood volume and oxygen consumption were significantly increased, and the OEF significantly reduced, while all these variables had significantly returned toward normality in the chronic-stage PET study. The ultimately infarcted area did not exhibit significant hyperperfusion in the acute stage. The areas with acute-stage hyperperfusion exhibited haemodynamic and metabolic abnormalities consistent with post-recanalization hyperperfusion, i.e. vasodilatation and "luxury perfusion'. Increased oxidative metabolism, previously reported only in animals, presumably reflects an overshoot of protein synthesis. The fact that the areas with hyperperfusion, though extensive, were topographically distinct from the infarcted region, suggests that spontaneous non-haemorrhagic hyperperfusion, when documented 5-18 h after onset, is a harmless and even perhaps beneficial phenomenon. These results have implications for clinical trials.

Aged↗
PubMed1996

Effects of isoniazid on ultrastructure of Mycobacterium aurum and Mycobacterium tuberculosis and on production of secreted proteins.

Isoniazid (INH), one of the most effective antimycobacterial drugs, specifically inhibits, at an early stage of its action, the biosynthesis of mycolic acids, specific mycobacterial lipids which play a central role in the cell envelope architecture of mycobacteria. In the present study, the consequences of the action of INH on the cell morphology of Mycobacterium tuberculosis and Mycobacterium aurum were examined. Electron microscopy was used to observe bacilli which were previously treated with either subinhibitory concentrations of INH or the MIC of the drug, leading to a decrease of 20 to 35% (by weight) of their mycolic acid contents. The earlier effect of INH on the ultrastructure of mycobacteria, as revealed by negative staining of bacilli, was the alteration of the bacterial poles; this event was observed prior to the bacteriostatic action of the drug and was accompanied by a release of material from the poles into the extracellular medium. In a later stage of the drug's action, cell deformation occurred and more extracellular material was seen. The material released following the action of the drug on susceptible mycobacterial cells was identified as being almost exclusively composed of proteins. Labeling of amino acids with 35S prior to and during the action of INH on M. aurum and subsequent analysis of the labeled proteins led to the conclusion that they consisted of secreted proteins which were up to 20-fold oversecreted in the presence of the drug. Competitive enzyme-linked immunosorbent assay with the secreted 45/47-kDa antigen complex of M. tuberculosis demonstrated up to 20-fold oversecretion of these proteins. Taken together, the production of oversecreted proteins following the decrease of the cell envelope mycolate content by INH strongly suggests that mycolic acids may act as a barrier in the export of proteins secreted by mycobacteria.

Antitubercular Agents↗
PubMed1996

Identification of the surface-exposed lipids on the cell envelopes of Mycobacterium tuberculosis and other mycobacterial species.

The surface-exposed lipids of Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium kansasii, Mycobacterium gastri, Mycobacterium smegmatis, and Mycobacterium aurum were isolated by gentle mechanical treatment of cells with glass beads. Analysis of the exposed lipids demonstrated a selective location of classes of ubiquitous lipids on the surfaces of mycobacteria. While phosphatidylethanolamine and phosphatidylinositol mannosides were exposed in all the species examined, dimycoloyl trehalose ("cord factor") was identified in the surface components of M. aurum only. Furthermore, monomycoloyl trehaloses and triacylglycerides were identified in the surface-exposed lipids of M. avium and M. smegmatis but not in those of the other mycobacterial species examined. The species- and type-species specific lipids were present on the mycobacterial cell surface: phenolic glycolipids, dimycocerosates of phthiocerols, and lipooligosaccharides were identified in the surface-exposed materials of M. tuberculosis (Canetti), M. kansasii, and M. gastri, whereas glycopeptidolipids were identified in the outermost lipid constituents of M. avium and M. smegmatis. This difference in the surface exposure of lipids of various mycobacterial species may reflect differences in their cell envelope organizations. Brief treatments of M. tuberculosis with Tween 80 prior to the use of glass beads led to erosion of regions of the capsule to expose gradually both cord factor and other lipids on the cell surface of the tubercle bacillus, demonstrating that the latter lipids are buried more deeply in the cell envelope and leading to the proposal of a scheme for the location of the capsular lipids of the tubercle bacillus.

Bacterial Capsules↗