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Biomedical subjects

J F Moreau

Publications and source records attributed to J F Moreau.

At least 37 records · Page 2Linked to original sources

[Comparison of endoscopic ultrasound and magnetic resonance imaging in severe pelvic endometriosis].

UNLABELLED: Deep pelvic endometriosis may lead to severe pain, the treatment of which may require complete surgical resection of lesions. Digestive infiltration is a difficult therapeutic problem. Preoperative diagnosis is difficult and digestive infiltration may remain unknown with incomplete resection and sometimes repeated surgery. Both magnetic resonance imaging (MRI) and endoscopic ultrasonography are able to detect rectosigmoid infiltration but their usefulness in the preoperative staging is still to be evaluated. The aim of this work was to evaluate and compare both techniques in the preoperative detection of deep pelvic endometriosis, particularly digestive infiltration. PATIENTS AND METHODS: From 1996 to 1998, 48 women with painful deep pelvic endometriosis had preoperative imaging exploration with endoscopic ultrasonography and MRI, and were operated on in order to attempt complete endometriosis resection. Patients were proposed for laparoscopic resection if endoscopic ultrasonography and/or MRI did not reveal digestive infiltration or for open resection if endoscopic ultrasonography and/or MRI were positive for digestive infiltration. RESULTS: Endoscopic ultrasonography and/or MRI led to suspicion of digestive endometriosis in 16 patients. Surgical resection was performed in 12 and digestive wall invasion was histologically demonstrated. At final follow-up, all patients had a dramatic decrease of their symptoms. The remaining 4 patients refused digestive resection and had only laparoscopic gynecologic resection. Infiltration although not histologically proven was very likely both on operative findings and clinical evolution. Digestive infiltration was preoperatively excluded in the 32 other patients. All had a laparoscopic treatment without digestive resection and pain diminished in all patients. In the 12 patients group who had digestive resection, digestive infiltration was correctly diagnosed by endoscopic ultrasonography in all cases (no false negative) whereas MRI, even with the use of endocoil antenna, led to correct diagnosis in 8 out of 12 cases. When endoscopic ultrasonography was negative for digestive infiltration, laparoscopic resection of lesions at surgery appeared complete in all cases. For the 16 patients with presumed digestive infiltration, sensitivity of endoscopic ultrasonography and MRI was 100 and 75% respectively, with a 100% specificity in both cases. MRI appeared very accurate for the detection of ovarian endometriotic locations. MRI was more sensitive but less specific than endoscopic ultrasonography for the diagnosis of isolated endometriotic recto-vaginal septum and utero-sacral ligaments lesions. CONCLUSION: Endoscopic ultrasonography was the best technique for the diagnosis of digestive endometriotic infiltration, which complicates the therapeutic strategy. MRI, however, allows more complete staging of other pelvic endometriotic lesions.

Adnexal Diseases↗

Implication of gammadelta T cells in the human immune response to cytomegalovirus.

In normal individuals, gammadelta T cells account for less than 6% of total peripheral T lymphocytes and mainly express T-cell receptor (TCR) Vdelta2-Vgamma9 chains. We have previously observed a dramatic expansion of gammadelta T cells in the peripheral blood of renal allograft recipients only when they developed cytomegalovirus (CMV) infection. This increase was long lasting (more than 1 year), was associated with an activation of gammadelta T cells, and concerned only Vdelta1 or Vdelta3 T-cell subpopulations. Analysis of gammadelta TCR junctional diversity revealed that CMV infection in these patients was accompanied by (a) a marked restriction of CDR3 size distribution in Vdelta3 and, to a lesser extent, in Vdelta1 chains; and (b) a selective expansion of Vdelta1 cells bearing recurrent junctional amino acid motifs. These features are highly suggestive of an in vivo antigen-driven selection of gammadelta T-cell subsets during the course of CMV infection. Furthermore, Vdelta1 and Vdelta3 T cells from CMV-infected kidney recipients were able to proliferate in vitro in the presence of free CMV or CMV-infected fibroblast lysates but not uninfected or other herpes virus-infected fibroblast lysates. This in vitro expansion was inhibited by anti-gammadelta TCR mAb's. These findings suggest that a population of gammadelta T cells might play an important role in the immune response of immunosuppressed patients to CMV infection.

Adolescent↗

Binding of leukemia inhibitory factor (LIF) to mutants of its low affinity receptor, gp190, reveals a LIF binding site outside and interactions between the two cytokine binding domains.

The gp190 transmembrane protein, the low affinity receptor for the leukemia inhibitory factor (LIF), belongs to the hematopoietin family of receptors characterized by the cytokine binding domain (CBD). gp190 is one of the very few members of this family to contain two such domains. The membrane-proximal CBD (herein called D2) is separated from the membrane-distal one (called D1) by an immunoglobulin-like (Ig) domain and is followed by three fibronectin type III repeats. We used truncated gp190 mutants and a blocking anti-gp190 monoclonal antibody to study the role of these repeats in low affinity receptor function. Our results showed that the D1Ig region was involved in LIF binding, while D2 appeared to be crucial for the proper folding of D1, suggesting functionally important interactions between the two CBDs in the wild-type protein. In addition, a point mutation in the carboxyl terminus of the Ig region strongly impaired ligand binding. These findings suggest that at least two distinct sites, both located within the D1Ig region, are involved in LIF binding to gp190, and more generally, that ligand binding sites on these receptors may well be located outside the canonical CBDs.

Animals↗

Leukaemia inhibitory factor expression is inhibited by glucocorticoids through post-transcriptional mechanisms.

Leukaemia inhibitory factor (LIF) is a pleiotropic cytokine which is involved in the regulation of the immune response and haematopoiesis. The authors investigated the regulation of the expression of LIF by glucocorticosteroids (GC). Endothelial cells (EC) constitutively produce LIF and this production is enhanced by interleukin 1 (IL-1). GC were found to inhibit the basal production of LIF by EC and to suppress its IL-1-induced augmentation. Whether corticosteroids suppress LIF production by blocking transcription of LIF mRNA, or by blocking LIF synthesis at a post-transcriptional level was examined. Northern blot hybridization analysis demonstrated that GC act mainly by decreasing the LIF mRNA level. In the presence of translation inhibitors a superinduction of LIF mRNA was observed. Dexamethasone (DEX) at a concentration of 1 microM was responsible for a rapid increase in the degradation rate of LIF mRNA which resulted in reducing its level by more than 50% within 2 h, whereas the transcription rate of LIF gene was not significantly altered in these conditions. These results demonstrated that GC inhibit LIF mRNA expression mainly by increasing the turnover rate of the LIF mRNA. The early LIF mRNA destabilizing activity of GC was translation dependent as shown by experiments with protein translation inhibitors. The results indicate that corticosteroids are inhibitors of LIF expression and that this inhibition mainly occurs through post-transcriptional mechanisms.

Actins↗

Varicocele: strategies in diagnosis and treatment.

Varicocele can be very easily diagnosed by physical examination and subsequently treated when it is painful or associated with testicular hypotrophy. However, palpability of the spermatic vein and reflux in low grade or even questionable varicoceles can be difficult to assess without imaging modalities. This can be a common problem for all physicians treating hypofertile men to decide whether the varicele needs to be treated or not. However, a gold standard that defines the presence of a subclinical varicocele has not yet been established. The different diagnostic tools based on ultrasonography investigated these past years to define a flow reversal in incontinent spermatic veins are presented in the first part of this review, with emphasis on subclinical varicocele. In the second part, we present our experience, together with a review of the literature concerning embolization of the spermatic veins as an alternative to surgery to treat varicoceles.

Blood Flow Velocity↗

Increase in CD3+ CD4- T lymphocytes in patients with AIDS and disseminated Mycobacterium avium-intracellulare complex infection: a prospective study. GECSA. Groupe d'Epidemiologie Clinique du SIDA en Aquitaine.

In a retrospective study, an increase in double-negative (CD3+ CD4- CD8-) (DN) T lymphocytes has been shown to be an independent predictor of disseminated Mycobacterium avium complex (D.MAC) infection in patients with less than 100 CD4+ T cells per mm3. To better characterize this cell expansion, a prospective study was designed. From July 1995 to April 1997, 206 HIV-infected patients with less than 100 CD4+ T cells per mm3 were prospectively followed up and immunophenotyped. The median followup was 1.1 year (+/-0.5 year), and 14 new D.MAC infections were diagnosed among 84 first AIDS-defining events. In univariate and multivariate analyses, D.MAC infections were the only opportunistic infection with a significant increase in DN T-cell percentage (median = 6.6; range = 1.7 to 24.5, P = 0.004) compared with patients without any opportunistic infection. This alteration in T-lymphocyte count could constitute a predictor for D.MAC infection in clinical practice.

AIDS-Related Opportunistic Infections↗

Th1 (IL-2, interferon-gamma (IFN-gamma)) and Th2 (IL-10, IL-4) cytokine production by peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE).

We investigated the production of IL-2, IFN-gamma, IL-10 and IL-4 by PBMC from 24 patients with SLE and 10 healthy individuals. Basal and mitogen-stimulated (lipopolysaccharide and phytohaemagglutinin (LPS + PHA)) cytokine production was determined in a whole blood assay (WBA). Supernatants were collected and assayed with specific ELISAs. Although the IL-2 and IFN-gamma contents did not differ significantly between patients and controls under both conditions, statistically significant correlations were found between each cytokine and disease activity (SLAM index) after stimulation (respectively, r = 0.501, P = 0.01 and r = 0.631, P = 0.001). PBMC IL-10 production was significantly higher for patients than controls (P = 0.05), but no correlation between IL-10 levels and the SLAM index was obtained. IL-4 production was not statistically different between SLE patients and controls. For stimulated WBAs, the IL-10/IL-2 and IL-10/IFN-gamma ratios were significantly correlated with disease severity (P = 0.02; P = 0.001, respectively). Overall, our data suggest that SLE is characterized by an elevated production of IL-10, reflecting the basal state of activation of the immune system. During exacerbation of SLE, IL-2 and IFN-gamma are synthesized in larger amounts and may cause the tissue damage observed.

Adolescent↗

Major expansion of gammadelta T lymphocytes following cytomegalovirus infection in kidney allograft recipients.

In normal persons, circulating gammadelta T cells comprise a minor cell subset (0.5%-6% of total lymphocytes). gammadelta T cells were studied in the context of therapeutic immunosuppression in transplanted patients. Flow cytometry detected an expansion of gammadelta T cells in 31 of 205 renal allograft recipients and in 2 of 41 uremic patients but in none of 45 healthy subjects. Univariate statistical analysis identified cytomegalovirus (CMV) infection (P<. 001), second graft (P<.001), and antithymocyte globulin treatment (P=.01) as three variables associated with high levels (>=6%) of circulating gammadelta T cells in allograft recipients. Multivariate analysis further indicated that CMV infection was the only independent parameter associated with >6% gammadelta T cells. gammadelta T cell expansion directly followed CMV infection and was never observed in persons who did not develop CMV infection. Thus gammadelta T cells may represent a first-line defense mechanism against CMV infection in a person whose alphabeta T cell response has been weakened by immunosuppression.

Adolescent↗

Magnetic resonance imaging characteristics of deep endometriosis.

The aim of this study was to describe magnetic resonance (MR) imaging findings in histopathologically proven deep endometriosis infiltrating the uterosacral ligaments, the pouch of Douglas, the rectum or the bladder. Twenty patients presenting with a clinical suspicion of deep endometriosis underwent preoperative MR imaging. Sagittal and axial fast T2- and axial T1-weighted spin echo MR sequences were performed. Four patients had post-contrast images. MR results, including morphology and signal intensity of each lesion, were compared to intraoperative gross appearance and histopathology. Histopathology diagnosed 24 lesions of deep endometriosis in the uterosacral ligaments (n = 12), the pouch of Douglas (n = 2), the rectum (n = 3), the bladder (n = 7). Uterosacral ligaments with deep endometriosis were statistically different from normal uterosacral ligaments for proximal nodularity (P = 0.001). There was no difference in signal intensity between normal and abnormal uterosacral ligaments. Contrast-enhanced SE images in four patients with detrusor invasion showed an interruption of the hypointense detrusor by the enhancing bladder endometriosis. Rectal endometriosis was missed in two of three patients and showed non-specific rectal wall thickening in one patient. It is concluded that MR imaging can diagnose deep endometriosis of uterosacral ligaments, the bladder and the pouch of Douglas, but lacks sensitivity in detecting rectal endometriosis without rectal distension.

Adult↗

An enlarged subpopulation of T lymphocytes bearing two distinct gammadelta TCR in an HIV-positive patient.

Although T cell clone monospecificity is ensured by several allelic exclusion processes operating at either the genotypic or phenotypic levels, clones expressing two distinct alphabeta or gammadelta TCR have been described in several instances. Thus far, the origin of dual TCR-expressing cells and the homeostatic mechanisms controlling the size of this subset in the periphery remain poorly understood. In the course of a phenotypic analysis of gammadelta T cells in HIV-infected patients, we detected the presence of a T cell subset stained by both Vdelta2- and Vdelta3-specific mAb, which represented a large fraction (up to 16.5%) of gammadelta peripheral blood lymphocytes (PBL) in one HIV patient. The presence of two distinct functional delta chains on these cells was confirmed by phenotypic and molecular analysis of TCR transcripts expressed by Vdelta2+Vdelta3+ T cell clones derived from this patient. For 18 months, the absolute number of these cells varied similarly to the other PBL subsets, before becoming undetectable in blood samples. Moreover, most of these cells expressed CD8 receptors, which are classically found on activated, but not resting, gammadelta T cells. Taken together, these data suggest that dual TCR-expressing T cells are subjected to peripheral expansions and contractions presumably following antigen recognition, which would argue against a systematic counter-selection of these cells during peripheral antigen-driven responses.

Antibodies, Monoclonal↗

Gammadelta T cells increase with Mycobacterium avium complex infection but not with tuberculosis in AIDS patients.

The aim of the present study was to better characterize the expansion of double-negative (DN) T cells in vivo in AIDS patients and to ascertain the discrepant response of an immunodepressed immune system towards two distinct mycobacterial infections. In a large cohort of HIV-1 seropositive patients with low CD4(+) T cell counts (<100/mm(3)), we have recently reported on an expansion of DN T cells which was observed only in patients with disseminated Mycobacterium avium infection, toxoplasmosis and Kaposi sarcoma, but not in patients with tuberculosis. The potential differential gammadelta T cells response observed in vivo in AIDS patients with tuberculosis or disseminated M. avium complex infection was investigated by collecting the concomitant or the closest T lymphocyte counts performed within 2 weeks of bacterial diagnosis of 112 disseminated M. avium infection and 41 tuberculosis patients. The DN and gammadelta T cell percentages were different between the two groups (P < 10(-4)) and the expansion of this compartment was found only with disseminated M. avium infections. An analysis of the variable delta2 segment versus pan-delta bearing T cells ratio disclosed a predominance of non-V(delta)2 T cells in these patients whose average values were identical in both groups. It is therefore concluded that the difference seen between these two types of mycobacterial infections concerning the DN T cells only involved the gammadelta T cells although the mechanism of their preferential expansion in disseminated M. avium infections remains a matter of speculation.

AIDS-Related Opportunistic Infections↗

Doppler ultrasonography of peripheral vascular disease: the potential for ultrasound contrast agents.

Noninvasive diagnosis of peripheral vascular disease started with the introduction of Doppler technology. The development of high frequency ultrasound and color Doppler imaging allows continuous assessment of vascular disorders along the arterial tree. However, the technique remains operator dependent. It also suffers from anatomic limitations, such as bowel gas and ultrasound attenuation due to depth or wall calcification. Ultrasound contrast agents increase the Doppler signal intensity and should therefore reduce the rate of technical failures. They are useful for detecting the flux in cases of attenuated ultrasound beam and reduced blood flow. Their administration using continuous infusion protocols increases the duration of the effect. New imaging modalities such as harmonic imaging and pulse inversion imaging reduce Doppler artifacts and allow real time detection of the microbubbles flowing in the blood stream. Future directions include ultrasound-guided therapy of occlusion using encapsulated drugs targeted to the thrombus.

Blood Flow Velocity↗

[Cystic tumors of the kidney in adults: radio-histopathologic correlations].

The purpose of this study is to provide an updated pathologic-radiologic classification of cystic renal tumors and to assess imaging diagnostic capabilities. Eighty seven cases of cystic renal tumors explored with multimodality imaging (ultrasonography, CT, MRI, arteriography) and with histopathologic correlation are reported. The most common cystic carcinomas were multilocular cystic renal cell carcinoma (33%) and the pseudocystic necrotic carcinoma (31%), which usually belong to category IV. Less common cystic carcinomas were unilocular cystic renal cell carcinoma (6%) and renal cyst wall carcinoma (6%). The association of thin septa and large locules are suggestive findings for multilocular cystic nephroma, but such criteria are not specific enough to recognize benign multilocular cystic nephroma and to exclude multilocular cystic renal cell carcinoma. Since carcinomatous degeneration may occur within the wall of such tumors, especially in von Hippel Lindau disease, surgery is still required. The results of our study corroborate the Bosniak classification of cystic renal masses: no tumors belonged to the category I or II, all cystic masses which belonged to the category IV were malignant tumors, category III included benign and malignant tumors.

Adult↗

[Imaging of thyroid nodules].

Ultrasonography and scintigraphy are the first line diagnostic imaging modalities for the evaluation of thyroid nodules. Scintigraphy provides functional informations, mainly detection of hot nodules. US provides accurate morphologic evaluation and it may sometimes suggest malignancy. US is the modality of choice for follow-up of non resected nodules and is very useful for guidance during biopsy. CT and MRI are mainly used for preoperative evaluation of thyroid nodules.

Biopsy, Needle↗