Biomedical subjects

Didier Martin

Publications and source records attributed to Didier Martin.

7 recordsLinked to original sources

PubMed2006

Long-term follow-up reveals low toxicity of radiosurgery for vestibular schwannoma.

AIM: The long-term effects of radiosurgery of vestibular schwannomas were investigated in a group of consecutively treated patients. METHODS AND MATERIALS: Between 1995 and 2001, 26 patients (median age: 67, range: 30-82) with a vestibular schwannoma were treated by Linac-based stereotactic radiosurgery (SRS). The median follow-up was 49 months (16-85 months). Only progressive tumours were treated. The median size of tumours was 18 mm (range 9-30 mm). Before SRS, 11 patients had a useful hearing (Gardner-Robertson classes 1 and 2). Single doses of 10-14 Gy were prescribed at the 80% isodose at the tumour margin. The follow-up consisted of regular imaging with MRI the first 3-6 months after the intervention, followed by additional yearly MRIs, a hearing test and a neurological examination. RESULT: The 5-year-probability of tumour control (defined as stabilization or decrease in size) was 95%. Five-year-probability of preservation of hearing and facial nerve function was 96% and 100%, respectively. Hearing was preserved in 10 out of 11 patients who had a normal or useful hearing at the time of treatment. Mild and transient trigeminal toxicity occurred in 2 (8%) patients. It appeared to be significantly correlated to the dose used (p=0.044). However, only a tendency to significance could be demonstrated in the relationship between the two factors when using the Cox analysis (hazard ratio=1.7; 95% CI: 0.7-3.9; p=0.23). CONCLUSIONS: With the doses used, our study demonstrates that SRS provides an equivalent tumour control rate when compared to surgery, as well as on a long-term basis, an excellent preservation of the facial and the acoustic nerves. Although no permanent trigeminal toxicity was observed, our data confirm that doses below 14 Gy can avoid transient dysesthesias.

Adult↗

PubMed2006

Chromosomal patterns of gene expression from microarray data: methodology, validation and clinical relevance in gliomas.

BACKGROUND: Expression microarrays represent a powerful technique for the simultaneous investigation of thousands of genes. The evidence that genes are not randomly distributed in the genome and that their coordinated expression depends on their position on chromosomes has highlighted the need for mathematical approaches to exploit this dependency for the analysis of expression data-sets. RESULTS: We have devised a novel mathematical technique (CHROMOWAVE) based on the Haar wavelet transform and applied it to a dataset obtained with the Affymetrix HG-U133_Plus_2 array in 27 gliomas. CHROMOWAVE generated multi-chromosomal pattern featuring low expression in chromosomes 1p, 4, 9q, 13, 18, and 19q. This pattern was not only statistically robust but also clinically relevant as it was predictive of favourable outcome. This finding was replicated on a data-set independently acquired by another laboratory. FISH analysis indicated that monosomy 1p and 19q was a frequent feature of tumours displaying the CHROMOWAVE pattern but that allelic loss on chromosomes 4, 9q, 13 and 18 was much less common. CONCLUSION: The ability to detect expression changes of spatially related genes and to map their position on chromosomes makes CHROMOWAVE a valuable screening method for the identification and display of regional gene expression changes of clinical relevance. In this study, FISH data showed that monosomy was frequently associated with diffuse low gene expression on chromosome 1p and 19q but not on chromosomes 4, 9q, 13 and 18. Comparative genomic hybridisation, allelic polymorphism analysis and methylation studies are in progress in order to identify the various mechanisms involved in this multi-chromosomal expression pattern.

Biomarkers, Tumor↗

PubMed2006

A phase 1-2, prospective, double blind, randomized study of the safety and efficacy of Sulfasalazine for the treatment of progressing malignant gliomas: study protocol of [ISRCTN45828668].

BACKGROUND: The prognosis of patients suffering from WHO grade 3 and 4 astrocytic glioma remains poor despite surgery, radiation therapy and the use of current chemotherapy regimen. Indeed, the median survival of glioblastoma multiforme (WHO grade 4) patients is at best 14.6 month with only 26.5 percent of the patients still alive after 2 years and the median survival of anaplastic astrocytomas (WHO grade 3) is 19.2 month. Recent evidence suggests that the transcription factor NF-kappaB is constitutively expressed in malignant gliomas and that its inhibition by drugs like Sulfasalazine may block the growth of astrocytic tumors in vitro and in experimental models of malignant gliomas. DESIGN: ULg_GBM_04/1 is a prospective, randomized, double blind single-center phase 1-2 study. A total of twenty patients with progressive malignant glioma despite surgery, radiation therapy and a first line of chemotherapy will be recruited and assigned to four dosage regimen of Sulfasalazine. This medication will be taken orally t.i.d. at a daily dose of 1.5-3-4 or 6 g, continuously until complete remission, evidence of progression or drug intolerance. Primary endpoints are drug safety in the setting of malignant gliomas and tumor response as measured according to MacDonald's criteria. An interim analysis of drug safety will be conducted after the inclusion of ten patients. The complete evaluation of primary endpoints will be conducted two years after the enrollment of the last patient or after the death of the last patient should this occur prematurely. DISCUSSION: The aim of this study is to evaluate the safety and efficacy of Sulfasalazine as a treatment for recurring malignant gliomas. The safety and efficacy of this drug are analyzed as primary endpoints. Overall survival and progression-free survival are secondary endpoint.

Administration, Oral↗

PubMed2006

Correlation of postmortem 9.4 tesla magnetic resonance imaging and immunohistopathology of the human thoracic spinal cord 7 months after traumatic cervical spine injury.

OBJECTIVE: To correlate high-resolution magnetic resonance imaging (MRI) with immunohistopathology in the injured human spinal cord. METHODS: Postmortem MRI scans at a field strength of 9.4 T, as well as standard histology and immunohistochemistry, were performed on an excised specimen of human high thoracic spinal cord, obtained 7 months after the initial trauma, several segments below a severe spinal cord lesion (C5). RESULTS: A precise correlation is described between MRI and immunohistochemistry of the long white matter tracts undergoing Wallerian degeneration and of an extension of the cervical lesion into the high thoracic cord. CONCLUSION: MRI, the only imaging technique that currently provides useful information on the spinal cord parenchyma after trauma, is rapidly evolving. High-field scanners of up to 9.4 T are being clinically tested. The present postmortem investigation of an isolated spinal cord specimen demonstrates the precise correlation that can be achieved between imaging and pathology. In future investigations, this type of technique can lead to a more precise description of spinal cord injuries and their consequences in remote tissue. Translation into the clinical setting will improve diagnosis and follow-up of spinal cord injured patients.

Adult↗

PubMed2004

Primary central nervous system lymphoma report of 32 cases and review of the literature.

We retrospectively analyzed 32 cases of primary central nervous system lymphoma (PCNSL). Five cases were diagnosed in the period 1987-1994, for 27 cases in the period 1995-2002. There were 17 men and 15 women whose median age was 69 years. Three patients were immunodeficient. The commonest symptoms were focal deficit (16 patients) and cognitive/behaviour disturbances (14 patients). Radiologically, a total of 47 contrast-enhancing lesions were observed in 32 patients; 18 patients had deep-seated lesions. All but two patients underwent histological diagnosis following craniotomy (11 patients) and/or stereotaxic biopsy (22 patients); diagnosis was obtained on CSF cytology in one patient with a third ventricle tumour. In the last patient, the diagnosis was based on the finding of marked tumour shrinkage under corticotherapy, despite two negative histological examinations. Treatment included surgical resection (10 patients), chemotherapy (25 patients) and/or radiotherapy (12 patients). According to the therapeutic recommendations of the GELA (Groupe d'Etude des Lymphomes de l'Adulte), 19 patients received at least two courses of high-dose methotrexate; intrathecal chemotherapy was used in 20 patients with methotrexate and/or cytosine arabinoside. Radiation therapy consisted of whole brain irradiation followed by a boost on tumour site. Nine patients received a combined treatment of chemotherapy and radiotherapy. Twelve patients showed rapid progression to death. At the time of last contact, 28/32 patients (88%) had died, all from PCNSL disease or from complications due to its treatment. The median survival time was 13.9 months. We conclude that PCNSL is an increasingly frequent tumour. The diagnosis is obtained by stereotactic biopsy in the majority of cases. The prognosis appears dismal despite an intensive multidisciplinary therapeutic approach.

Adult↗

PubMed2003

Retrograde reactions of Clarke's nucleus neurons after human spinal cord injury.

Successful axon regeneration depends on the expression of regeneration-associated genes by axotomized neurons. Here, we demonstrate, for the first time to our knowledge, the expression of regeneration-associated genes by axotomized human CNS neurons. In situ hybridization and immunohistochemistry showed a transient induction of GAP-43 and c-jun in Clarke's nucleus neurons caudal to traumatic human spinal cord injury. These results support experimental data that nonregenerating central nervous system neurons can temporarily upregulate regeneration-associated genes, reflecting a transient regenerative capacity that fails over time.

Caspase 3↗

PubMed2002

Acute traumatic central cord syndrome: magnetic resonance imaging and clinical observations.

OBJECT: Acute traumatic central cord syndrome has been classically thought to be caused by a hemorrhage that primarily affects the central part of the spinal cord and that destroys the axons of the inner part of the corticospinal tract devoted to the motor control of the hands. Some authors, however, have proposed that its pathogenesis is based on the destruction of the motor neurons supplying the muscles of the hand. To test the validity of these two theories, the authors retrospectively studied the magnetic resonance (MR) images obtained in 18 cases of acute traumatic central cord syndrome (ATCCS) to assess the presence of intramedullary blood and to define the distribution of the abnormal signal intensities in the cervical spinal cord. METHODS: The authors used the American Spinal Injury Association (ASIA) motor scale to assess upper- and lower-limb deficits and to evaluate its metameric distribution. The abnormal intramedullary signal was then compared with the distribution of the motor deficit. All MR imaging sessions performed in the acute stage revealed a hyperintense signal on T2-weighted sequences without any signal change suggesting the presence of intramedullary blood. The localization of this signal was distributed predominantly from the C3-4 to the C5-6 disc levels. The mean ASIA motor score was 74.3 of 100, with an unequal representation between the upper and lower limbs (32 of 50 compared with 42.3 of 50, respectively). The metameric distribution of the deficit was also unequal, with a major deficit in hand function (C8-T1) compared with the more proximal cord segments (5.2 of 10 compared with 7.8 of 10, respectively). This demonstrates the absence of any correlation between the hyperintense signal and the motor deficit distribution. CONCLUSIONS: Acute traumatic central cord syndrome cannot be explained by the injury to the gray matter at the level of motor neurons supplying the hand muscles. In agreement with recently published data, the results of this series confirm the absence of intramedullary hemorrhage and corroborate the hypothesis that ATCCS may be explained by the impairment of the corticospinal tract, which can be affected globally.

Acute Disease↗