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Biomedical subjects

Jean-François Michiels

Publications and source records attributed to Jean-François Michiels.

13 recordsLinked to original sources

Ectopic bone formation using an injectable biphasic calcium phosphate/Si-HPMC hydrogel composite loaded with undifferentiated bone marrow stromal cells.

We have used a new synthetic injectable composite constituted of hydroxyapatite/tricalcium phosphate (HA/TCP) particles in suspension in a self-hardening Si-hydroxypropylmethylcellulose (HPMC) hydrogel. The aim of this study was to evaluate in vivo the biocompatibility and the new bone formation efficacy of this scaffold loaded with undifferentiated bone marrow stromal cells (BMSCs). This biomaterial was mixed extemporaneously with BMSCs prepared from C57BL/6 mice, injected in subcutaneous and intramuscular sites and retrieved 4 and 8 weeks after implantation. Dissection of the implants revealed a hard consistency and the absence of a fibrous capsule reflecting a good integration into the host tissues. Histological analysis showed mineralized woven bone in the granule inter-space with numerous active osteoclasts attached to the particles as assessed by the presence of multinucleated cells positively stained for TRAP activity and for the a3 subunit of the V-ATPase. Small vessels were homogenously distributed in the whole implants. Similar results were obtained in SC and IM sites and no bone formation was observed in the control groups when cell-free and particle-free transplants were injected. These results indicate that this injectable biphasic calcium phosphate-hydrogel composite mixed with undifferentiated BMSCs is a new promising osteoinductive bone substitute. It also provides with an original in vivo model of osteoclast differentiation and function.

Animals↗

[An unusual and misleading form of pilocytic astrocytoma].

Pilocytic astrocytoma is histologically characterized by a biphasic pattern. We report a myxoid form of frontocallosal pilocytic astrocytoma in a 13-year-old girl. MRI showed a relatively well-defined tumor with necrosis and ring-like zone of contrast enhancement. Histological examination showed a monophasic tumor composed of piloid cells on a myxoid background corresponding to a pilomyxoid astrocytoma. This unusual form of pilocytic astrocytoma can be mistaken for a high grade infiltrating glioma. Pilomyxoid astrocytoma is more aggressive than classic pilocytic astrocytoma and has to be distinguished from it.

Adolescent↗

Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma.

Hereditary predisposition to neuroblastoma accounts for less than 5% of neuroblastomas and is probably heterogeneous. Recently, a predisposition gene has been mapped to 16p12-p13, but has not yet been identified. Occurrence of neuroblastoma in association with congenital central hypoventilation and Hirschsprung's disease suggests that genes, involved in the development of neural-crest-derived cells, may be altered in these conditions. The recent identification of PHOX2B as the major disease-causing gene in congenital central hypoventilation prompted us to test it as a candidate gene in familial neuroblastoma. We report a family with three first-degree relatives with neuroblastic tumours (namely two ganglioneuromas and one neuroblastoma) in one branch and two siblings with Hirschsprung's disease in another branch. A constitutional R100L PHOX2B mutation was identified in all three patients affected with tumours. We also report a germline PHOX2B mutation in one patient treated for Hirschsprung's disease who subsequently developed a multifocal neuroblastoma in infancy. Both mutations disrupt the homeodomain of the PHOX2B protein. No loss of heterozygosity at the PHOX2B locus was observed in the tumour, suggesting that haplo-insufficiency, gain of function or dominant negative effects may account for the oncogenic effects of these mutations. These observations identify PHOX2B as the first predisposing gene to hereditary neuroblastic tumours.

Adult↗

Three-dimensional culture and differentiation of human osteogenic cells in an injectable hydroxypropylmethylcellulose hydrogel.

The present work evaluates a newly developed silated hydroxypropylmethylcellulose (Si-HPMC)-based hydrogel as a scaffold for 3D culture of osteogenic cells. The pH variation at room temperature catalyzes the reticulation and self-hardening of the viscous polymer solution into a gelatine state. We designed reticulation time, final consistency and pH in order to obtain an easy handling matrice, suitable for in vitro culture and in vivo injection. Three human osteogenic cell lines and normal human osteogenic (HOST) cells were cultured in 3D inside this Si-HPMC hydrogel. We show here that osteosarcoma cells proliferate as clonogenic spheroids and that HOST colonies survive for at least 3 weeks. Mineralization assay and gene expression analysis of osteoblastic markers and cytokines, indicate that all the cells cultured in 3D into this hydrogel, exhibited a more mature differentiation status than cells cultured in monolayer on plastic. This study demonstrates that this Si-HPMC hydrogel is well suited to support osteoblastic survival, proliferation and differentiation when used as a new scaffold for 3D culture and represents also a potential basis for an innovative bone repair material.

Bone Substitutes↗

[An unusual tumor of the adrenal gland].

Adenomatoid tumors are benign mesothelial tumors that usually affect the genital tract. We report the case of a 65-year-old man with an adenomatoid tumor of the adrenal gland. This uncommon location and its histological heterogeneity can lead to a mistaken diagnosis of malignant tumor. Positive cells with mesothelial markers in immunohistochemistry improve diagnosis. The proper identification of this benign tumor in the adrenal gland and the knowledge of its differential diagnosis deserve attention to avoid invasive treatment.

Adenocarcinoma↗

[A solitary tumor of the common bile duct: case report of a metastatic melanoma].

Primary malignant melanoma of the bile duct is very rare. We report a case of a malignant melanoma involving the common bile duct in a 41-year-old man. The patient presented to the hospital with an isolated jaundice and underwent pancreaticoduodenectomy. Absolute exclusion of a metastatic tumor is not entirely possible.

Adult↗

Multifilament polypropylene mesh for urinary incontinence: 10 cases of infections requiring removal of the sling.

One hundred and forty-nine women received a suburethral woven polypropylene mesh insertion for urodynamic stress incontinence. Eleven patients (7.5%) presented between 4 and 17 months after surgery (mean 10 months) with symptoms of retropubic infection. Ten patients required surgical exploration, drainage of the collection and removal of the tape either unilaterally (six) or bilaterally (four). Bacterial cultures were negative in nine women. Following removal of the tape, eight patients reported residual incontinence, either stress leakage (five) or de novo urge incontinence (three). Multifilament polypropylene meshes appear to be more at risk of infection, usually requiring sling removal, which may be related to pore size of the mesh. Our data reinforce the importance of proper evaluation of new surgical procedures by rigorously designed randomised trials with adequate follow up to identify rare but potentially serious complications.

Adult↗

Impact of antiretroviral treatment on progression of hepatic fibrosis in HIV/hepatitis C virus co-infected patients.

BACKGROUND: The impact of immune reconstitution on liver fibrosis in HIV/hepatitis C virus (HCV) patients is unknown. In this case-control study, we investigated the impact of HIV infection on the severity of liver fibrosis and identified related factors. METHODS: We studied 116 HIV/HCV patients and 235 HCV only patients all untreated for HCV. Each co-infected patient was matched with two singly-infected patients according to gender, age at contamination and duration of infection. Liver biopsy was analysed using the METAVIR score. RESULTS: Alcohol consumption and route of contamination differed between HCV-infected and HCV/HIV co-infected patients. Among co-infected patients, a F3-F4 Metavir score was significantly more frequent than in mono-infected patients. Co-infected patients with severe fibrosis (F3-F4) had higher transaminase, ferritin levels and lower CD4 T-cell count than patients with none to moderate fibrosis (F0-F2). Although median duration of treatment with nucleoside analogues, non-nucleoside analogues and protease inhibitors were comparable in both groups, the delay between the presumed date of contamination and treatment initiation with highly active antiretroviral therapy (HAART) was significantly longer for patients with severe fibrosis than those with none to moderate fibrosis. Finally, the mean rate of fibrosis progression was significantly slower among patients exposed to HAART. CONCLUSION: Early antiretroviral therapy in co-infected HIV-HCV patients may slow liver fibrosis progression.

Adolescent↗

Elastofibroma of the stomach.

We report the case of a 76-year-old woman who presented with abdominal pain caused by a gastric tumor. The stomach was resected and found to have developed an elastofibroma. The lesion was yellowish, unencapsulated, and characterized histologically by abundant collagen fibers mixed with numerous elastic serrated fibers. Elastofibromatous change of the gastrointestinal tract is a rare event.

Aged↗

[Primary pleomorphic rhabdomyosarcoma of the kidney in adults: unusual tumor].

Primary rhabdomyosarcoma (RMS) of the kidney in an adult is a very rare and unusual tumor in this site. The clinical signs associated with the flank tumoral syndrome, the histologic appearance of cytoplasmic double striation in rhabdomyoblasts and the immunohistochemical expression of skeletal muscle differentiation (desmin, myoglobin, myogenin) are described in the context of a rapidly evolving renal RMS in a 77-year old man. The differential diagnosis are mainly represented by sarcomatoid renal cell carcinoma. According to the neoplastic extent, the treatment includes radical nephrectomy, chemotherapy and surgery. The prognosis of primary renal RMS is extremely poor, with lymph node, hepatic, bone marrow and pulmonary metastasis and a short survival rate.

Aged↗

[Registry of liver biopsies from hepatitis C infected patients in the Alpes-Maritimes (France). Results from the first 2 years].

OBJECTIVE: To perform a descriptive analysis of patients with chronic hepatitis C based on a local registry of liver biopsies. PATIENTS AND METHOD: Collection of clinical, biological and histological data from all HCV-infected patients who underwent liver biopsy between January 1997 and December 1998 in the Alpes-Maritimes (France). RESULTS: One thousand and fifty six patients including 924 who lived in the Alpes-Maritimes (515 male, 409 female, mean age: 44.9 years old) were included. Intravenous drug use (30.1%) was the major suspected source of infection before blood transfusion (28.2%). Among intravenous drug users, 38% of patients were infected with genotype 1a and 37.4% with genotype 3. The METAVIR fibrosis severity score was distributed as follows: F0: 10.8%, F1: 53.7%, F2: 15.9%, F3: 14.7%, and F4: 4.9%. In a multivariate analysis adjusted for the duration of infection, independent risk factors associated with the severity of fibrosis were age at contamination >=30 years, genotype other than 1a and alcohol intake >=50 g/day. Determination of HCV antibody and liver biopsy were performed an average of 12.5 and 14 years after presumed date of contamination, respectively. CONCLUSIONS: These data provide a clearer view of the impact of this condition in this area and could help to define a comprehensive policy for patient management.

Adult↗