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Biomedical subjects

G Marchal

Publications and source records attributed to G Marchal.

At least 19 recordsLinked to original sources

Recombinant bacillus Calmette-Guérin as a potential vector for preventive HIV type 1 vaccines.

In August 1997, the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) convened an expert working group to discuss current strategies for the development of HIV type 1 vaccines. Based on the recent findings of investigators from Japan's National Institute of Infectious Diseases (NIID) in Tokyo using recombinant bacillus Calmette-Guérin (rBCG) as a potential vectored vaccine for HIV, a recommendation was made that further work in this area is a priority. As a result, the working group reconvened in September 1998 to discuss the progress to date with this vaccine approach, as well as areas of related research to assess the feasibility of a BCG-vectored HIV vaccine. This report summarizes the discussions addressing the available scientific data on the potential use of rBCG as a vector for preventive HIV vaccines, the work necessary to move such candidate vaccines into Phase 1 clinical trials, and recommendations targeted at facilitating the long-term development of rBCG-vectored HIV vaccines.

AIDS Vaccines↗

Immunogenicity and protective capacity of Mycobacterium bovis BCG after oral or intragastric administration in mice.

After oral or intragastric administration of BCG to mice, comparable numbers of IFN gamma and TNF gamma producing cells were detected in both local (Peyer's patches) and central (spleen) lymphoid organs. Similar levels of precursors of CD8+ cytotoxic T lymphocytes specific for mycobacterial antigens were also found in the spleen and the mesenteric lymph nodes. These immune responses remained high over the course of 3 months, the duration of observation. Oral administration of BCG led to an enlargement of the cervical lymph nodes, which contained high levels of viable bacteria. In contrast, no adverse effects were observed in mice given the BCG via the intragastric route. These two routes of immunization induced similar levels of protective immunity to those observed in mice immunized via the subcutaneous route against a challenge with a virulent Mycobacterium tuberculosis strain (H37Rv).

Administration, Oral↗

Attention to speed of motion, speed discrimination, and task difficulty: an fMRI study.

We studied the functional neuroanatomy of attention to speed of motion using functional magnetic resonance imaging in eight healthy subjects, who performed a speed discrimination (SID) task using a random textured pattern moving at a reference speed of 6 deg/s. During the control condition (DIM), with retinal stimulation identical to that during SID, subjects detected the dimming of the central fixation point. Attention to speed (SID compared to DIM) activated mainly ventral V3 and V4, dorsal V3 and V3A. Compared to a fixation control condition, speed discrimination recruited a large visuomotor network, including hMT/V5+. However, hMT/V5+ was only marginally more active during speed discrimination than during dimming detection. Thus hMT/V5+ is involved in speed discrimination, in line with the speed discrimination impairments following hMT/V5+ lesions, but our results suggest that this activity simply reflects the processing of motion rather than attention to speed. Manipulating the difficulty of the speed discrimination task over a large range of the psychometric curve revealed that increasing difficulty linearly increases activity in right frontal regions, as well as in lateral occipital and dorsal parietal regions. A weak effect of difficulty was also observed in dorsal V3.

Adult↗

Magnetic resonance imaging in the assessment of urologic disease: an all-in-one approach.

The aim of this study was to evaluate an "all-in-one" MR procedure to examine the kidneys, the renal vascular supply and renal perfusion, and the urinary tract. In 64 patients (58 with urologic disease and 6 healthy volunteers), MR was performed including: (a) T1- and T2-weighted imaging; (b) 3D contrast-enhanced MR angiography (MRA), including the renal arteries, renal veins, as well as renal perfusion; and (c) 3D contrast-enhanced MR urography (MRU) in the coronal and sagittal plane. For the latter, low- and high-resolution images were compared. Prior to gadolinium injection, 0.1 mg/kg body weight of furosemide was administered intravenously. The results were compared with correlative imaging modalities (ultrasonography, intravenous urography, CT), ureterorenoscopy and/or surgical-pathologic findings. Visualization of the renal parenchyma, the vascular supply, and the collecting system was adequate in all cases, both in nondilated and in dilated systems and irrespective of the renal function. One infiltrating urothelial cancer was missed; there was one false-positive urothelial malignancy. Different MR techniques can be combined to establish an all-in-one imaging modality in the assessment of diseases which affect the kidneys and urinary tracts. Continuous refinement of the applied MR techniques and further improvements in spatial resolution is needed to expand the actual imaging possibilities and to create new tracts and challenges in the MR evaluation of urologic disease.

Adult↗

Treatment of VX2 liver tumor in rabbits with "wet" electrode mediated radio-frequency ablation.

Radio-frequency ablation (RFA) has been considered as an alternative therapy for liver tumors. A "wet" electrode with interstitial infusion of hypertonic saline was tested for the RFA of liver tumor in rabbits. Seventy-eight liver tumors ( 1.5 to 3.0 cm) were induced in 41 rabbits by VX2 carcinoma implantation. Fifty-one tumors in 27 rabbits were treated with RFA. Under laparotomy, the RF energy was delivered while 5 % saline was infused through the electrode into the tumor at 1 ml/min. Six rabbits with 12 tumors were treated with only intratumoral 5 % saline infusion without RFA. Another 8 rabbits with 15 tumors received sham operation as untreated controls. The efficacy of the therapy was evaluated with survival rate, MRI, microangiography, and histopathology. In the RFA group, 6 rabbits survived longer than 6 months (absolute eradication rate 22.2 %); 12 rabbits were found free of viable tumor at the moment when they were sacrificed (relative eradication rate 44.4 %); 9 rabbits showed local tumor relapse and/or lung metastasis 2-10 weeks after ablation (recurrent rate 33.3 %). In control groups of saline infusion and sham operation, all 14 rabbits died within 3 months (mortality rate 100 %). Three-month survival rates between RFA group and control groups were significantly different (p < 0.05). Findings of MRI, microangiography, and histology supported these outcomes. Radical treatment of liver malignancy in rabbits is possible with the present modified RFA technique. Its clinical usefulness has to be further proven.

Animals↗

A novel "cooled-wet" electrode for radiofrequency ablation.

In the light of growing demands for improved applicability of radiofrequency ablation (RFA), recently we have developed a novel "cooled-wet" electrode by taking the advantages of both internally cooled and saline-enhanced electrodes. The efficacy of the electrode was evaluated in both ex vivo and in vivo liver RFA under both low and high power output levels. The ablation volume created with the "cooled-wet" electrode appeared to be much larger than that reported up to now with the use of other monopolar electrodes. The mechanisms on how this device optimizes the RF energy delivery are also discussed.

Animals↗

Multiple small pseudoaneurysms complicating pancreatitis: angiographic diagnosis and transcatheter embolization.

We report a case of retroperitoneal hemorrhage due to multiple, small pseudoaneurysms complicating a chronic alcoholic pancreatitis. Cross-sectional imaging with CT and US could not clearly depict these vascular lesions. Selective arteriography of the superior mesenteric and gastroduodenal arteries clearly showed the small pseudoaneurysms and definitive treatment was performed by transcatheter embolization using coils. Eight months after successful embolization, the patient is asymptomatic without any recurrent bleeding.

Aneurysm, False↗

Remote myocardial dysfunction after acute anterior myocardial infarction: impact of left ventricular shape on regional function: a magnetic resonance myocardial tagging study.

OBJECTIVES: We sought to evaluate regional morphology and function in patients in their first week after having a reperfused anterior myocardial infarction (MI) using magnetic resonance (MR) myocardial tagging. BACKGROUND: The mechanism of myocardial dysfunction in the remote, noninfarct-related regions is an unresolved issue to date. METHODS: Sixteen patients with a first reperfused transmural anterior MI were studied with MR tagging at 5 +/- 2 days after the event, and the results were compared with those of an age-matched control group regions. The left ventricle (LV) was divided into infarct, adjacent and remote regions. Magnetic resonance tagging provided information on the regional ventricular morphology and function. RESULTS: Morphologically, an increase of the circumferential radius of curvature was found in the remote myocardium, whereas the longitudinal radius of curvature was increased in all regions of the LV. A significant increase in apical sphericity was also found. A significant reduction in strain and function was found not only in the infarct region, but also in the adjacent and remote myocardium. The loss in regional ejection fraction in the remote myocardium (61.4 +/- 11.7% in patients vs. 68.7 +/- 10.0% in control subjects, p < 0.0001) was related to a significant reduction of the longitudinal and circumferential strain, whereas systolic wall thickening was preserved. CONCLUSIONS: Remote myocardial dysfunction contributes significantly to the loss in global ventricular function. This could be secondary to morphologic changes in the infarct region, leading to an increased systolic longitudinal wall stress without loss of intrinsic contractility in the remote regions.

Adult↗

A comparative study on validation of a novel cooled-wet electrode for radiofrequency liver ablation.

RATIONALE AND OBJECTIVES: A cooled-wet electrode has been developed for radiofrequency ablation (RFA) that allows simultaneous internal-cooling perfusion ("cooled") and interstitial hypertonic saline infusion ("wet"). The present comparative study was conducted to validate this new device for the increased coagulation volume in RFA. METHODS: Under low-power (50 W, groups A through F) and high-power (90 W, groups A' through F') control modes, 240 RFA lesions were created on excised beef liver to compare the cooled-wet electrode with other monopolar electrodes. The experimental regimens were as follows: groups A and A', conventional RF electrode; groups B and B', cooled electrode; groups C and C', wet electrode; groups D and D', cooled-wet electrode; groups E and E', cooled-wet electrode but suspended wet function; and groups F and F', cooled-wet electrode but suspended cooled function. The ablation efficacy was evaluated by comparing the lesion sizes as well as parameters of impedance, power output, current, and tip temperature. RESULTS: With lower impedance and tip temperature but higher power output, the lesion size in groups D (4.90 +/- 0.60 cm) and D' (6.6 +./- 0.99 cm) was significantly larger than that in other groups. CONCLUSIONS: The use of the cooled-wet electrode could efficiently increase the lesion size for liver ablation.

Animals↗

Mycobacterium bovis BCG induces similar immune responses and protection by rectal and parenteral immunization routes.

We compared cellular immune responses to rectal, subcutaneous, and intradermal administration of Mycobacterium bovis BCG for 5 to 20 weeks in mice, guinea pigs, and macaques. Strong lymphoproliferative responses were induced in spleen cells after in vitro stimulation with purified protein derivative in guinea pigs and macaques, whatever the route of immunization. Comparable high numbers of gamma interferon- and tumor necrosis factor alpha-producing cells were found in the spleen after rectal, subcutaneous, and intradermal immunization of mice and macaques. Similar levels of precursors of cytotoxic T lymphocytes specific for mycobacterial antigens were observed in mice for all immunization routes. In macaques, cytotoxic activity, determined only at the end of the experiment (20 weeks), was similar after rectal and intradermal immunization. Six months after immunization, rectal and subcutaneous routes induced in mice similar levels of protective immunity against challenge with a virulent Mycobacterium tuberculosis strain (H37Rv). Rectal immunization gave immune responses and protective capacity similar to those for parenteral immunization and seemed to be a promising new route of vaccination against tuberculosis; in our study, immunization via the rectal route never induced side effects associated with parenteral routes (axillary adenitis) and could also effectively reduce the risks of viral transmission associated with unsafe injections in the developing world.

Administration, Rectal↗

Breath-hold contrast-enhanced three-dimensional MR angiography of the abdomen: time-resolved imaging versus single-phase imaging.

PURPOSE: To evaluate a technique for time-resolved breath-hold contrast material-enhanced three-dimensional magnetic resonance (MR) angiography of the abdomen. MATERIALS AND METHODS: In a prospective study, 43 patients underwent time-resolved MR angiography (acquisition time per data set, 7 seconds). The patients also underwent single-phase high-spatial-resolution MR angiography (acquisition time, 27 seconds) (n = 6), conventional angiography (n = 7), or both (n = 30). No bolus timing study was performed for time-resolved MR angiography. Image quality (presence of artifacts, ability to prevent venous overlap on arterial phase images, contrast enhancement) and demonstration of anatomic variants (renal arterial and venous variants, vena caval anomaly, visceral arterial variants) and vascular diseases were assessed. RESULTS: Time-resolved MR angiographic images were characterized by fewer and less severe artifacts, less overlap of enhancing veins, and better contrast enhancement than were single-phase MR angiographic images (P < .05). The mean sensitivity and specificity were 90% (nine of 10) and 100% (1 73 of 1 73), respectively, for detection of arterial anatomic variants and 93% (28 of 30) and 100% (324 of 325), respectively, for detection of disease. The technique also proved to be reliable for demonstration of venous disease. CONCLUSION: In comparison with current non-time-resolved MR angiographic techniques, time-resolved MR angiography is more robust and easier to perform and allows simultaneous evaluation of arterial and venous disease.

Abdomen↗

Focal liver lesions: evaluation of the efficacy of gadobenate dimeglumine in MR imaging--a multicenter phase III clinical study.

PURPOSE: To evaluate gadobenate dimeglumine (Gd-BOPTA) for dynamic and delayed magnetic resonance (MR) imaging of focal liver lesions. MATERIALS AND METHODS: In 126 of 214 patients, MR imaging was performed before Gd-BOPTA administration, immediately after bolus administration of a 0.05- mmol/kg dose of Gd-BOPTA, and 60-120 minutes after an additional intravenously infused 0.05-mmol/kg dose. In 88 patients, imaging was performed before and 60-120 minutes after a single, intravenously infused 0.1-mmol/kg dose. T1- and T2-weighted spin-echo and T1-weighted gradient-echo images were acquired. On-site and blinded off-site reviewers prospectively evaluated all images. Intraoperative ultrasonography, computed tomography (CT) during arterial portography, and/or CT with iodized oil served as the reference methods in 110 patients. RESULTS: Significantly more lesions were detected on combined pre- and postcontrast images compared with on precontrast images alone (P <. 01). All reviewers reported a decreased mean size of the smallest detected lesion and improved lesion conspicuity on postcontrast images. All on-site reviewers and two off-site reviewers reported increased overall diagnostic confidence (P <.01). Additional lesion characterization information was provided on up to 109 (59%) of 184 delayed images and for up to 50 (42%) of 118 patients in whom dynamic images were assessed. Gd-BOPTA would have helped change the diagnosis in 99 (47%) of 209 cases and affected patient treatment in 408 (23%) of 209 cases. CONCLUSION: Gd-BOPTA increases liver lesion conspicuity and detectability and aids in the characterization of lesions.

Adult↗

Predictive power of individual genetic and environmental factor scores.

This study explores the use of an individual's genetic (IGFS) and environmental factor score (IEFS), constructed using genetic model fitting of a multivariate strength phenotype. Maximal isometric and dynamic strength measures, one maximal repetition load (1RM) and muscle cross-sectional area (MCSA) were measured in 25 monozygotic and 16 dizygotic twin pairs. The use of IGFS and IEFS in predicting the sensitivity to environmental stress was evaluated by the association of the scores with strength training gains after a 10-week high resistance strength training programme. Results show a high contribution of genetic factors to the covariation between maximal strength and muscle cross-sectional area (84-97%) at pre-training evaluation. Individual factor scores explained the largest part of the variation in IRM and other strength measures at pre-training and post-training evaluation respectively. Genes that are switched on due to training stress (gene-environment interaction) could explain the decrease in explained variation over time. A negative correlation was found between IGFS and strength training gains (-0.24 to -0.51, P < 0.05); individuals with a high IGFS tend to gain less strength than individuals with low IGFS. Individual environmental factor scores have lower differential power. The predictive value of the IGFS has potential utility in identifying an individual's susceptibility to environmental stress in a variety of multifactorial characteristics, eg diseases and impairments, and for selection of sib pairs for QTL analyses.

Adolescent↗

45/47 kilodalton (APA) antigen capture and antibody detection assays for the diagnosis of tuberculosis.

SETTING: APA complex (45/47 kDa) is an antigen specifically excreted by Mycobacterium tuberculosis and could therefore be a good candidate for diagnosis. OBJECTIVES: To develop three APA immunocapture ELISA assays using monoclonal antibodies (Mabs) and one IgG anti-APA ELISA test, and to determine their usefulness for the diagnosis of tuberculosis in Madagascar. DESIGN: For the Ag assays, 23 negative sputum and serum samples and 64 pairs of sputum and serum from active smear-positive patients (PTM+) were tested. For antibody assay, 116 negative controls, 143 PTM+ and 54 extra-pulmonary tuberculosis patients were tested. RESULTS: The sensitivities of the APA antigen detection assays were low (less than 40%) for a specificity of 95.6%, using either monoclonal antibodies or clinical specimens. The anti-APA serology was more sensitive (76.9% for PTM+ patients) but less specific (73.2%). Due to their poor predictive values, these tests cannot be recommended for the routine diagnosis of tuberculosis in Madagascar.

Antibodies, Bacterial↗

Review of MR mammography techniques.

Many of the new techniques of MRI have promising characteristics for the further improvement of sensitivity and specificity but there remains a large place for clinical trials to evaluate the practical value of the different new approaches. The authors review the general MRI rules that determine image quality and comment on the use-fullness of innovations in MR mammography.

Breast Diseases↗

Decreased capacity of recombinant 45/47-kDa molecules (Apa) of Mycobacterium tuberculosis to stimulate T lymphocyte responses related to changes in their mannosylation pattern.

The Apa molecules secreted by Mycobacterium tuberculosis, Mycobacterium bovis, or BCG have been identified as major immunodominant antigens. Mass spectrometry analysis indicated similar mannosylation, a complete pattern from 1 up to 9 hexose residues/mole of protein, of the native species from the 3 reference strains. The recombinant antigen expressed in M. smegmatis revealed a different mannosylation pattern: species containing 7 to 9 sugar residues/mole of protein were in the highest proportion, whereas species bearing a low number of sugar residues were almost absent. The 45/47-kDa recombinant antigen expressed in E. coli was devoid of sugar residues. The proteins purified from M. tuberculosis, M. bovis, or BCG have a high capacity to elicit in vivo potent delayed-type hypersensitivity (DTH) reactions and to stimulate in vitro sensitized T lymphocytes of guinea pigs immunized with living BCG. The recombinant Apa expressed in Mycobacterium smegmatis was 4-fold less potent in vivo in the DTH assay and 10-fold less active in vitro to stimulate sensitized T lymphocytes than the native proteins. The recombinant protein expressed in Escherichia coli was nearly unable to elicit DTH reactions in vivo or to stimulate T lymphocytes in vitro. Thus the observed biological effects were related to the extent of glycosylation of the antigen.

Amino Acid Sequence↗

Murine natural killer T(NKT) cells [correction of natural killer cells] contribute to the granulomatous reaction caused by mycobacterial cell walls.

Mice injected with deproteinized cell walls prepared from the strain H37rv of Mycobacterium tuberculosis develop a granuloma-like lesion in which NKT cells are predominant. NKT cells play a primary role in the granulomatous response, because the latter does not occur in Jalpha281(-/-) mice, which miss NKT cells. The glycolipidic fraction of the cell walls is responsible for the recruitment of NKT cells; the recruiting activity is associated with fractions containing phosphatidylinositolmannosides. These results define a powerful experimental set up for studying the in vivo induction of NKT cell responses to microbial components.

Animals↗