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Biomedical subjects

J F Michiels

Publications and source records attributed to J F Michiels.

At least 19 recordsLinked to original sources

Long-term outcome of oligodendrogliomas.

BACKGROUND: Favorable prognostic factors for oligodendroglial tumors include age younger than 40 years, low tumor grade, and extent of resection. OBJECTIVE: To assess survival time and prognostic factors of 100 patients with oligodendrogliomas diagnosed between 1995 and 2002. METHODS: The tumors were rated histologically by the WHO classification as low grade (grade II) or anaplastic (grade III). One hundred patients were categorized into three groups: group A: grade II, group B: secondary grade III (low grade with anaplastic transformation during the follow-up), group C: de novo grade III. All patients were symptomatic at presentation and underwent neurosurgical procedure for histologic diagnosis. Follow-up was performed with clinical assessment, brain MRI, and MIBI scintigraphy. RESULTS: There were 66 men and 34 women (mean age at diagnosis 46.7 years). The most common first symptom was partial epileptic seizure (75%). Fifty-six patients had initial gadolinium enhancement (A: 15.6%; B: 36.8% as grade II, 95% as grade III; C: 90%), generally associated with MIBI hypermetabolism (p < 0.0001). Survival rates at 2, 5, and 10 years were A: 88%, 88%, 85%; B: 79%, 64%, 42%; C: 43%, 16%, 15%. CONCLUSIONS: Secondary anaplastic oligodendroglioma patients were younger than patients with de novo anaplastic oligodendrogliomas. Histologic confirmation is mandatory because some low grade oligodendrogliomas had gadolinium enhancement on MRI and some anaplastic did not. Survival time was longer for secondary than for de novo anaplastic oligodendrogliomas without difference in the duration of the malignant phase of the disease.

Adolescent↗

Alteration of striatal dopaminergic function induced by glioma development: a microdialysis and immunohistological study in the rat striatum.

Tumoral growth effects on brain circuitry and neurochemical activities remain poorly documented. This study evaluates C6 graft effects on striatal dopaminergic afferent projections at both anatomical and functional levels. Immunohistochemistry was performed to investigate changes in neurofilament (NF), tyrosine hydroxylase (TH) and dopamine transporter (DAT) expression. Dopaminergic turnover was assessed using multiprobe microdialysis in freely-moving rat. In C6 graft striatum, dopamine (DA) catabolites were reduced in glioblastoma (DOPAC: -61%, HVA: -62%). In contrast, the DA level remained unchanged. Staining for NF, TH and DAT was drastically decreased inside the tumor. Our histological data report that striatal tumoral growth is associated with a decrease in the density of dopaminergic endings which can explain, at least in part, the decrease in DA turnover. The decrease in DAT transporter expression and the lack of change in DA level may result from an increase in DA diffusion from the peripheral areas of the tumor. In conclusion, glioblastoma growth has major consequences on the local neuronal circuitry and its neurochemistry. Changes in inter-connections and neurotransmitter turnover may result in abnormal neuronal firing activity and participate in clinical disorders associated with glioblastoma diagnosis.

3,4-Dihydroxyphenylacetic Acid↗

Disrupted traffic of connexin 43 in human testicular seminoma cells: overexpression of Cx43 induces membrane location and cell proliferation decrease.

Connexins, the constitutive proteins of gap junctions, are considered to be tumour suppressive agents and are often impaired in the tumourigenic processes. In the present study, the expression of connexin 43 (Cx43), which is involved in the control of spermatogenesis through Sertoli/germ cell coupling, has been investigated in human testicular seminoma cells (tumours and the JKT-1 cell line). Cx43 was immunolocalized in the Golgi apparatus without membrane expression and was detected by immunoblotting in JKT-1 as exclusive 70 kD bands. No mutation could be found by sequencing the transcript obtained by RT-PCR. Transfection with a Cx43-V5 vector reproduced the same gel shift, identifying these 70 kD bands as Cx43. The Cx43-70 kD bands were also expressed in normal testicular tissue, associated with the classical 43 kD isoforms. Stable transfection of JKT-1 with a Cx43-GFP vector allowed restoration of Cx43 membrane expression, functional cell coupling, and inhibition of the cell proliferation rate. Storage of Cx43 in the Golgi apparatus may correspond during spermatogenesis to an intermittent physiological process that becomes permanent in malignant seminoma cells as a result of the tumourigenic process. By preventing Cx43 membrane expression, this disrupted traffic may itself participate in tumour promotion.

Adult↗

[Neoadjuvant chemotherapy for symptomatic non operable grade II fibrillary astrocytoma in adults].

We collected 6 case-reports of symptomatric non removable low grade fibrillary astrocytoma of adults treated with a procarbazine-CCNU-vincristine chemotherapy regimen. All patients had drug-resistant epilepsy but brain imaging was stable. Total gross resection was rejected because of Volume or tumor location. After 4 to 7 cycles of chemotherapy, 2 patients had partial response and one minor response on brain MRI. All of them were seizure-free. Progression free survival was not reached at 5 Years. Up-front chemotherapy for low-grade astrocytomas may be useful and has to be prospectively evaluated.

Adult↗

In vivo involvement of polymorphonuclear neutrophils in Leishmania infantum infection.

BACKGROUND: The role of lymphocytes in the specific defence against L. infantum has been well established, but the part played by polynuclear neutrophil (PN) cells in controlling visceral leishmaniasis was much less studied. In this report we examine in vivo the participation of PN in early and late phases of infection by L. infantum. RESULTS: Promastigote phagocytosis and killing occurs very early after infection, as demonstrated by electron microscopy analyses which show in BALB/c mouse spleen, but not in liver, numerous PN harbouring ultrastructurally degraded parasites. It is shown, using mAb RB6-8C5 directed against mature mouse granulocytes, that in chronically infected mice, long-term PN depletion did not enhance parasite counts neither in liver nor in spleen, indicating that these cells are not involved in the late phase of L. infantum infection. In acute stage of infection, in mouse liver, where L. infantum load is initially larger than that in spleen but resolves spontaneously, there was no significant effect of neutrophils depletion. By contrast, early in infection the neutrophil cells crucially contributed to parasite killing in spleen, since PN depletion, performed before and up to 7 days after the parasite inoculation, resulted in a ten-fold increase of parasite burden. CONCLUSIONS: Taken together these data show that neutrophil cells contribute to the early control of the parasite growth in spleen but not in liver and that these cells have no significant effect late in infection in either of these target organs.

Animals↗

ALK probe rearrangement in a t(2;11;2)(p23;p15;q31) translocation found in a prenatal myofibroblastic fibrous lesion: toward a molecular definition of an inflammatory myofibroblastic tumor family?

A prenatal tumor located in the lumbar paravertebral area was discovered during a routine ultrasound examination at 32 weeks of pregnancy and surgically removed at 4 months of life. The histopathological diagnosis was first suggested to be an infantile desmoid fibromatosis. The tumor karyotype showed a three-way translocation involving both chromosomes 2 and a chromosome 11, t(2;11;2)(p23;p15;q31). Fluorescence in situ hybridization with a probe flanking the ALK gene at 2p23 demonstrated a rearrangement, as previously described in inflammatory myofibroblastic tumors (IMTs). In light of the genetic analysis, the histopathological diagnosis was revised to IMT, although inflammatory cells were scarce. IMTs are pseudosarcomatous inflammatory lesions that primarily occur in the soft tissue and viscera of children and young adults. Our report describes for the first time the occurrence of IMT during prenatal life. The ALK rearrangement may represent the molecular definition of a subgroup of mesenchymal tumors, not always with complete morphological features of IMT, similar to the model of EWS rearrangement in the Ewing sarcoma family of tumors.

Adult↗

Expression of LSLCL, a new C-type lectin, is closely restricted, in bone marrow, to immature neutrophils.

In vitro, LSLCL is expressed by numerous myeloid, promyelocytic, and T or B lymphoblastoid cell lines. In vivo, LSLCL is strongly expressed in bone marrow and only faintly in lymphoid organs. We show here that, in bone marrow, LSLCL is detected: (i) concentrated in the cytoplasm of immature neutrophils but not in myeloblasts nor in mature neutrophils, (ii) in extracellular bone marrow fluid. Besides, numerous cDNAs, similar to LSLCL (identity of 93-99%), are found in 'expressed sequence tags' databases from various origins, mostly fetal and undifferentiated tumour tissues. Since LSLCL and various closely related cDNAs are expressed at definite stages of cellular maturation processes, we hypothesize that this class of proteins could play an important role in the control of cellular differentiation.

Animals↗

Interstitial granulomatous drug reaction with a histological pattern of interstitial granulomatous dermatitis.

The interstitial granulomatous drug reaction (IGDR) is a novel drug-associated entity, characterized by violaceous plaques with a predilection for skin fold areas. Light microscopically, it resembles the incipient diffuse interstitial phase of granuloma annulare. Differentiating light microscopic features include the absence of complete collagen necrobiosis, the presence of interface dermatitis, and variable lymphoid atypia. The lack of vasculitis rules out the extravascular necrotizing granuloma (Winkelmann granuloma) associated with systemic disease. The differential diagnosis with interstitial granulomatous dermatitis with arthritis as defined by Ackerman et al. has not been studied until now. Our aim was to determine the histologic criteria allowing us to differentiate IGDR without interface dermatitis and lymphoid atypia from interstitial granulomatous dermatitis. We report three patients with IGDR triggered, in two cases by respectively angiotensin convertin enzyme (ACE) inhibitors and furosemide, and in one case by the association of an ACE inhibitor, furosemide, and fluindione. Histologic examination showed a histological pattern of interstitial granulomatous dermatitis. We found a dense, diffuse histiocytic infiltrate distributed interstitially and in palisaded array within the reticular dermis. Eosinophils and some neutrophils were scattered throughout the infiltrate. In some tiny foci, enveloped by histiocytes, thick collagen bundles associated with basophilic nuclear debris or "flame figures" were seen. Vasculitis, interface dermatitis, or lymphoid atypia were absent. Our study allowed us to expand the histological spectrum of IGDR including a histological pattern similar to interstitial granulomatous dermatitis. The lack of degenerated collagen could be a subtle clue in favor of interstitial granulomatous dermatitis triggered by a drug.

Aged↗

Vertebral metastases from pineoblastoma.

Two male patients aged 26 and 18 years presented with vertebral metastases originating from pineoblastomas on which surgery had been performed 8 years and 5 months earlier, respectively. In the first case in which the metastasis developed in the T8 corpus, the disease is presently under control after high-dose chemotherapy and autologous blood stem cell transplantation. The second patient (sacral metastasis), despite aggressive adjuvant therapy, died 2 years after the last operation because of spinal seeding. These uncommon cases are discussed with reference to the literature on extraneural metastases that originate from neuroepithelial tumors of the central nervous system.

Adolescent↗

Pelvic ependymoma arising from the small bowel.

A 37-year-old woman underwent resection of an abdominal tumour which was adherent to the wall of the ileum. The diagnosis of an ependymoma was supported by evidence of typical perivascular pseudorosettes which stained positive for glial fibrillary acidic protein and contained abundant intermediate filaments within the elongated processes by electron microscopy. Flow cytometric study showed a diploid population of tumour cells. This is the first case of an ependymoma arising from the small bowel without any connection to the genital tract, the omentum or with the sacroccygeal area. As is the case with other unusual and ectopic localisations of ependymomas, prognosis of this tumour is difficult to evaluate.

Adult↗

[Prospective study comparing ultrasonography guided trans-rectal biopsy and finger guided trans-perineal biopsy in the diagnosis of prostatic cancer].

OBJECTIVE: To compare ambulatory ultrasound-guided transrectal biopsy and finger-guided transperineal biopsy. MATERIAL AND METHODS: From June 1997 to October 1999, 51 patients were simultaneously biopsied by the two techniques and by the same operator, 30 min after antibiotic prophylaxis with 200 mg of Ciprofloxacin by intravenous injection. Transperineal biopsies were performed first, followed by ultrasound-guided transrectal biopsies. Six cores were obtained with each technique, from the apex, the middle and the base of each lobe. RESULTS: For a PSA level between 4 and 10 ng/ml, 6 cancers were detected in 23 patients (26%) and one cancer was only detected via the transrectal route. For a PSA level greater than 10 ng/ml, 17 cancers were detected in 28 patients (60%), 15 (53%) by transperineal biopsy and 11 (39%) by transrectal biopsy. Six cancers were only detected by transperineal biopsy and two were only detected by transrectal biopsy. No statistically significant difference was observed between the numbers of positive biopsies obtained with the two techniques. CONCLUSION: The use of ultrasonography is not essential to perform systematic biopsies. Rather than the technique used, the detection of prostate cancer is improved by performing 12 cores instead of 6.

Aged↗

[Factors influencing recurrence and role of radiotherapy in filum terminale ependymomas. 14 cases and review of the literature].

PURPOSE: We reviewed a series of 14 cases of filum terminale ependymoma and 264 cases in the literature, to study the characteristics of these tumors and specifically to determine factors influencing recurrence. MATERIAL AND METHODS: This series analyzed data between 1984 and 1998. The mean follow-up period was 5.5 years and the median age 40 years. Pain was the first symptom, except in one case, with progressive sensitive-motor deficit. Four patients had a myelography and a CT scan, and ten a MRI. All patients were operated with a total resection in 12 cases. All tumors, except one, were a myxopapillary ependymoma. RESULTS: Clinical results were excellent in 2 cases, good in 8, stable in 2 and worse in 2. Two patients had a recurrence after an initial sub-total resection, both were operated on again, followed by post-operative radiotherapy. Among the 278 filum terminale ependymoma, removal was total in 200 (72%). A recurrence occurred in 15% of them after total removal, and in 43% after partial removal (p<0.001). Among patients with partial removal, recurrence was observed in 33% of them if they had post-operative radiotherapy, and in 55% of them if they did not have post-operative radiotherapy (p<0.05). CONCLUSION: The extent of tumor removal has a statistically significant effect upon recurrence. This review is in favor of post-operative radiotherapy in case of partial removal, but this systematic attitude can be discussed after a critical analysis of this study. Long term follow-up is mandatory due to the possibility of late recurrence.

Adult↗

In vivo study of tumor metabolism: an application of new multi-probe microdialysis system in the striatum of freely moving rats grafted with C6 cells.

The purpose of this study is to investigate the in vivo tumoral brain metabolism in free moving rats using microdialysis. Cells from C6 glioma cell line were inoculated in one striatum 15 days before the microdialysis experimentation. Then, using a new system allowing perfusion of several microdialysis probes in free moving rat, normalised dialysate levels of glucose, lactate and pyruvate were monitored in both glioma and control striatum. At the end of the procedure, animals were sacrificed for histological study. Data shows that probe functioning is similar in both tissues. The results for normalised glucose level were in striatum control: 2.14 mM, in tumoral striatum: 1.71 mM (P>0.1); for lactate, respectively, 0.86 and 1.65 mM (P<0.05) and for pyruvate, respectively, 65.56 and 140. 94 microM (P<0.05). This data clearly shows a significant increase of pyruvate and lactate in tumoral striatum compared to normal striatum, correlating previous in vitro studies on glioma metabolism. We conclude that this microdialysis technique is of value in tumoral brain and could constitute an interesting tool for a better understanding of glioma metabolism.

Animals↗

Trial of oral fumagillin for the treatment of intestinal microsporidiosis in patients with HIV infection. ANRS 054 Study Group. Agence Nationale de Recherche sur le SIDA.

OBJECTIVE: Intestinal microsporidiosis caused by Enterocytozoon bieneusi is a cause of chronic diarrhoea in patients with HIV infection for which there is no current therapy. This study was designed to assess the safety and efficacy of oral fumagillin in this infection. DESIGN: A dose-escalation trial. METHODS: Twenty-nine HIV-infected patients with E. bieneusi infection were consecutively enrolled in the trial. Oral doses of fumagillin were given to four groups of patients for 14 days: 10 mg/day (group 1), 20 mg/day (group 2), 40 mg/day (group 3), and 60 mg/day (group 4). Patients were seen at weeks 1, 2, 4 and 6 to assess safety and efficacy. Efficacy was assessed primarily by the clearance of microsporidia from stools and follow-up duodenal biopsies. RESULTS: Thirteen patients complained of abdominal cramps, vomiting or diarrhoea during the study, and three patients had fumagillin withdrawn because of adverse events. Thrombocytopenia, neutropenia and hyperlipasaemia were the most frequent biological adverse events. Twenty-one out of 29 patients transiently cleared microsporidia from their stools during the study. By week 6, however, all patients in groups 1, 2 and 3 had parasitic relapse. Interestingly, eight out of 11 (72%) patients treated with 60 mg/day (group 4) apparently cleared microsporidia from their gastrointestinal tract and gained weight. No parasitic relapse was documented in these eight patients during a mean follow-up of 11.5 months. CONCLUSION: Treatment with fumagillin at 60 mg/day for 14 days has promise as an effective oral treatment for E. bieneusi infections.

AIDS-Related Opportunistic Infections↗

Fluorescence in situ hybridization study of aneuploidy of chromosomes 7, 10, X, and Y in primary and secondary glioblastomas.

The aneuploidy of autosomes 7, 10, and sex chromosomes (X and Y) was analyzed in a series of 44 primary (de novo) and 20 secondary glioblastomas using fluorescence in situ hybridization (FISH) on smear preparations of glioma tissue. The tumors were screened for trisomy 7, monosomy 10, as well as loss of the Y chromosome and disomy of the X chromosome in male subjects, and monosomy of the X chromosome in female subjects. We found that taken alone or in combination, these chromosomal abnormalities do not appear to be characteristic of a glioblastoma subtype; therefore, they do not allow the differentiation between primary and secondary glioblastomas. Also, the loss of a chromosome 10 appears to be an earlier event than a gain of a chromosome 7 for the genesis of a secondary glioblastoma.

Aneuploidy↗

The histological spectrum of visceral leishmaniasis caused by Leishmania infantum MON-1 in acquired immune deficiency syndrome.

Visceral leishmaniasis (VL) due to Leishmania infantum is endemic in Southern France and can be considered as an opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS). Co-infection with Leishmania sp. and human immunodeficiency virus (HIV) is emerging, but pathological findings of leishmaniasis in AIDS have been poorly documented, and scattered case reports have include morphological descriptions. The clinicopathologic analysis of 16 patients with HIV and VL were evaluated. The clinical presentation was characteristic of VL, with fever, hepatosplenomegaly, and pancytopenia in 6 patients, and the diagnosis was confirmed by finding amastigotes of Leishmania sp. in bone marrow smears and biopsy specimens. In 4 patients, the initial diagnosis of VL was made fortuitously in gastrointestinal biopsies performed systematically (3 patients) or in case of diarrhea (1 patient). In one duodenal biopsy, Leishmania sp. and Mycobacteria sp. were associated. Liver biopsy allowed the diagnosis of VL in 3 cases. Autopsy was performed in 9 patients, showing a disseminated leishmaniasis with very unusual localizations (adrenal and heart) in 2 cases. Cutaneous leishmaniasis involvement was noted before (4 patients), at the same time (2 patient), or after (1 patient) the diagnosis of VL. Inflammatory infiltrates noted with Leishmania sp. infection were made by CD68 macrophages with (8 patients) or without (8 patients) associated CD8 positive lymphocytes. Immunoperoxidase study using polyclonal anti-Leishmania sp. antibodies contributed to the diagnosis in all cases. Electron microscopy of 2 digestive biopsy specimens showed the ultrastructural characteristics of Leishmania sp. amastigotes. The zymodeme MON-1 of L infantum was identified by isoenzyme electrophoresis in all patients. The mean of CD4 counts was 37/mm3 at the time of diagnosis, and the mean duration before the death was 8 months. As shown in this study, VL in AIDS can be diagnosed in gastrointestinal or liver biopsies. Diagnosis of VL was made when the CD4 count was very low and was correlated with a poor prognosis.

AIDS-Related Opportunistic Infections↗

Nephrogenic adenofibroma in a young child.

Nephrogenic adenofibroma is a benign renal tumor in children and young adults described by Hennigar and Beckwith in 1992. Seven cases have been described, and we report the first case in an 11-month-old child, in good health, revealed by a macroscopic hematuria. Nephrogenic adenofibroma is an unusual tumor, which was difficult to distinguish from nephroblastoma and mesoblastic nephroma. Beckwith makes a distinction between this principal differential diagnosis in child renal tumors based upon morphologic and immunohistochemical patterns. In our observation, the diagnosis remained difficult and needed several reviews of our case. Beckwith proposed the final diagnosis: nephrogenic adenofibroma with stromal predominance. The prognosis is excellent and no treatment is indicated. A FISH analysis of the tumor cells found a trisomy 11. Trisomy 11 has been reported in mesoblastic nephroma as the most frequent chromosomal abnormality. This finding in tumor cells provides an argument for excluding the diagnosis of nephroblastoma but can not clarify the difference between nephrogenic adenofibroma and mesoblastic nephroma.

Adenofibroma↗

Medical treatment of a pacemaker endocarditis due to Candida albicans and to Candida glabrata.

We describe a case of pacemaker infection due to two fungal species: Candida albicans and C. glabrata. Transthoracic echocardiography showed a large vegetation on the intraventricular wires. Because of severe underlying diseases, surgery was believed to be contraindicated. The patient was treated using high dose of fluconazole, resulting in clinical improvement and negative blood cultures. However, 2 months later, the patient underwent a fatal stroke. At autopsy, a large vegetation was found only all along the wires. Postmortem culture of the infected material was positive for both C. albicans and C. glabrata.

Aged↗