A mesenchymal glioma stem cell profile is related to clinical outcome.

Recent studies have demonstrated a relationship between the expression of stem cell-associated genes and relapses in glioblastoma (GBM), suggesting a key role for tumor stem cells in this process. Although there is increasing interest in this field, glioma stem cells (GSCs) are still poorly characterized, their 'stemness' state and factors maintaining these properties remain largely unknown. We performed an expression profiling analysis of pluripotency in gliomaspheres derived from 11 patients. Comparative analysis between GSCs and H1 and H9 human embryonic stem cells as well as H9-derived neural stem cells indicates major variations in gene expression of pluripotency factors Nanog and OCT4, but a stable pattern for SOX2 suggesting its important function in maintaining pluripotency in GSCs. Our results also showed that all GSC lines have the capacity to commit to neural differentiation and express mesenchymal or endothelial differentiation markers. In addition, hierarchical clustering analysis revealed two groups of GSCs reflecting their heterogeneity and identified COL1A1 and IFITM1 as the most discriminating genes. Similar patterns have been observed in tumors from which gliomaspheres have been established. To determine whether this heterogeneity could be clinically relevant, the expression of both genes was further analyzed in an independent cohort of 30 patients with GBM and revealed strong correlation with overall survival. In vitro silencing of COL1A1 and IFTM1 confirmed the effect of these mesenchymal-associated genes on cell invasion and gliomasphere initiation. Our results indicate that COL1A1 and IFITM1 genes could be considered for use in stratifying patients with GBM into subgroups for risk of recurrence at diagnosis, as well as for prognostic and therapeutic evolution.

Cell transplantation in the damaged adult brain.

Parkinson's disease (PD) is the most common movement disorder in Europe, affecting more than two million people between 50 and 70 years of age. The current therapeutic approaches are of symptomatic nature and fail to halt the progressive neurodegenerative course of the disease. The development of innovative and complementary approaches to promote cellular repair may pave the way for disease-modifying therapies which may lead to less suffering for the patients and their families and finally to more cost-effective therapies. To date, cell replacement trials in PD aiming at replacing lost dopamine neurons were mainly focused on placing the transplanted cells within the target site, the striatum, and not within the lesioned site, the substantia nigra (SN). This was based on the misconception that the adult brain constitutes a non-permissive barrier not allowing the outgrowth of long distance axons originating from transplanted embryonic neurons. A growing body of evidence is challenging this concept and proposing instead to place the graft within its ontogenic site. This has been performed in several lesional animal models for various traumatic or neurodegenerative pathologies of the brain. For instance, transplanted neurons within the lesioned motor cortex were shown to be able to send distant and appropriate projections to target areas including the spinal cord. Similarly, in an animal model of PD, mesencephalic embryonic cells transplanted within the lesioned SN send massive projections to the striatum and, to a lesser extent, the frontal cortex and the nucleus accumbens. This has lead to the proposal that homotopic transplantation may be an alternative in cell-based therapies as transplanted neurons can integrate within the host brain, send projections to target areas, restore the damaged circuitry, increase neurotransmitter levels and ameliorate behavior. We will discuss also the potential of replacing embryonic neuronal cells by stem cell derived neurons as the use of embryonic cells is not without an ethical and logistical burden; in this line many have thrived to derive neurons from embryonic stem cells (ESC) in order to use them for cell transplantation. These studies are already yielding important information for future approaches in the field of cell therapies in PD but also in other neurodegenerative disorders where cell transplantation therapy may be considered. While the field of cell replacement therapies has been recently called into question with contrasting results in transplanted PD patients, these new sets of findings are raising new hopes and opening new avenues in this rejuvenated field.

Flagellar radial spoke protein 3 is an A-kinase anchoring protein (AKAP).

Previous physiological and pharmacological experiments have demonstrated that the Chlamydomonas flagellar axoneme contains a cAMP-dependent protein kinase (PKA) that regulates axonemal motility and dynein activity. However, the mechanism for anchoring PKA in the axoneme is unknown. Here we test the hypothesis that the axoneme contains an A-kinase anchoring protein (AKAP). By performing RII blot overlays on motility mutants defective for specific axonemal structures, two axonemal AKAPs have been identified: a 240-kD AKAP associated with the central pair apparatus, and a 97-kD AKAP located in the radial spoke stalk. Based on a detailed analysis, we have shown that AKAP97 is radial spoke protein 3 (RSP3). By expressing truncated forms of RSP3, we have localized the RII-binding domain to a region between amino acids 144-180. Amino acids 161-180 are homologous with the RII-binding domains of other AKAPs and are predicted to form an amphipathic helix. Amino acid substitution of the central residues of this region (L to P or VL to AA) results in the complete loss of RII binding. RSP3 is located near the inner arm dyneins, where an anchored PKA would be in direct position to modify dynein activity and regulate flagellar motility.

High incidence of anti-heparin/platelet factor 4 antibodies after cardiopulmonary bypass surgery.

Fifty-one patients undergoing cardiopulmonary bypass (CPB) were studied on day 0 and day 8 for heparin-induced thrombocytopenia (HIT). The platelet aggregation test (PAT) and tests for anti-heparin-platelet factor 4 (anti-H.PF4), anti-IL8 and anti-neutrophil activating peptide 2 (anti-NAP2) antibodies (Ab) were performed by ELISA. On day 8, 27% of patients were positive for anti-H.PF4Ab. None of these results were found to influence thrombotic complications or platelet counts after CPB. Our results suggest that IgG to H.PF4 may be considered a risk factor, but that additional factors must be required for HIT to develop. We conclude that assays based on platelet activation would be more appropriate for the diagnosis of HIT after CPB.

Risk of early controlateral carotid endarterectomy.

Between January 1984 and January 1994, we performed early endarterectomy of the controlateral carotid on 94 patients within a delay of 1 to 8 days after the first endarterectomy. Lesions were symptomatic in 58 patients (62%) and asymptomatic in 36 patients (38%). Eighty-four operations were performed under cervical block anesthesia (89%), eight under general anesthesia, and two under local anesthesia (2%). Severe intraoperative hypertension occurred in seven patients (7%) including five under cervical block anesthesia (6%) and two under general anesthesia (25%). Two patients (2.1%) died of stroke secondary to carotid thrombosis in one case and hyperperfusion syndrome in one case. Morbidity included one transient ischemic attack (1%) and one myocardial infarction (1%). Postoperative control of patency revealed asymptomatic occlusion of the internal carotid artery in two patients, accounting for one of the two deaths. Our findings demonstrate that neurologic mortality/morbidity is not higher after early controlateral carotid endarterectomy than unilateral endarterectomy.

[Estimation of the treatment cost of cervical cancer]. / Estimation du coût du traitement du cancer du col de l'utérus.

BACKGROUND: The goal of this study was to estimate direct costs induced by the first year of treatment of cervix cancers according to the stage at diagnosis. METHODS: Fifteen patients of the Gynaecology Department of the Besançon hospital (Doubs, France) were involved in a prospective study to estimate the real cost of treatment of carcinomas in situ (CIS) by conization and of microinvasive carcinomas (MIC) by simple hysterectomy. Costs of invasive cancers were obtained from a retrospective analysis of 24 hospital records in the Radiotherapy Department. RESULTS: The average real cost of treatment for the CIS was 5023 FF (1995 French Francs). Real treatment cost of the MIC was 15,867 FF. The average cost of treatment for the IB and IIA cancers stage (FIGO classification) was 61,540 FF and 145,314 FF for the IIB to IV stage cancers. CONCLUSIONS: Cost-estimation of cervix cancer treatment according to the stage of diagnosis has to be done before starting a cost-effectiveness analysis of mass screening for cervix cancers. This study will allow us to take into account changes in the stages distribution following on a screening campaign.

[Mandibular metastasis of hepatocellular carcinoma. Apropos of 3 cases]. / Métastases mandibulaires des carcinomes hépato-cellulaires. A propos de 3 observations.

Three cases of mandibular metastasis of hepatocellular cancer are reported. The specific characteristics are described: rarity, discovery, localization, haemorrhagic biopsies and histological criteria. Prognosis is poor.

[Our experience using free vascularized bone flaps in mandibular reconstruction. The external brachial flap, the fibular flap, the para-scapular flap]. / Notre expérience des lambeaux libres vascularisés osseux dans les reconstructions mandibulaires. Le lambeau brachial externe, le lambeau fibulaire, le lambeau parascapulaire.

New techniques developed over the last decade use vascularized bone flaps for maxillofacial reconstructive surgery. Indications for use of three recently described flaps (external brachial, fibular, parascapular) are discussed as a function of the regions to be reconstructed. Three clinical cases are presented, each patient having received one type of flap.

[Carcinoma of the oral cavity independent of tobacco and alcoholic beverages. Apropos of 23 cases in elderly persons]. / Les carcinomes de la cavité buccale indépendants du tabac et des boissons alcooliques. A propos de 23 cas chez des personnes âgées.

Twenty-three cases of carcinomas of the buccal cavity have been observed and treated in persons aged more than 60 years, for whom tobacco and alcoholic drinks, the usual factors of these carcinomas, were not involved. The result of these treatments indicates that the vital and functional prognosis is relatively favorable in these persons, who are free from any alcohol- or tobacco-induced affections.

Cervical epidural anaesthesia for carotid artery surgery.

A series of 394 patients (251 men, 143 women; mean age 70.0 +/- 8.4 yr) selected for carotid artery surgery (CAS) performed under cervical epidural anaesthesia (CEA) was analysed retrospectively. Carotid endarterectomy was performed in 326 patients and saphenous vein bypass in 68. The cervical epidural administration of 15 ml 0.5 per cent bupivacaine or 0.37-0.40 per cent bupivacaine plus fentanyl (50-100 micrograms) resulted in an effective sensory blockade from C2 to T4-T8. Patients were maintained awake during the surgical procedure in comfortable condition. Serious complications included dural puncture in two patients, epidural venipuncture in six patients and respiratory muscle paralysis in three patients. Hypotension (10.9 per cent) and bradycardia (2.8 per cent) were the most frequent side-effects of CEA. Transient neurological events were noticed in 84 patients during the surgical procedure. A definite neurological deficit occurred postoperatively in 12 patients. Three patients suffered postoperative myocardial infarction. The mortality rate was 2.3 per cent (nine patients). Carotid artery surgery may be performed under CEA but haemodynamic variables should be monitored closely and managed closely during the procedure.

[Prognostic and therapeutic aspects of lympho-epithelial lesions of the parotid. Apropos of 8 cases]. / Aspects pronostiques et thérapeutiques des lésions lympho-épithéliales de la parotide. A propos de 8 observations.

The so-called benign lympho-epithelial lesion (BLEL) of the parotid is a rare condition. Its diagnosis is based on histology. For a long time there have been problems with its classification and prognosis: classification since certain cases may be classified as Sjögren's syndrome or as a precursor of the latter, prognosis there may be recurrence, contralateral involvement or progression to non-hodgkin's lymphoma. The authors discuss these factors in 8 cases and propose total parotidectomy with facial nerve preservation as the treatment of choice.

[Cervical epidural anesthesia in carotid artery surgery]. / Anesthésie péridurale cervicale dans la chirurgie carotidienne.

A series of 394 patients who underwent surgery of the carotid artery under cervical extradural anaesthesia is presented. With this technique the patient remains conscious throughout the operation, which facilitates neurological monitoring. Due to failure or complication, extradural anaesthesia was abandoned and replaced by general anaesthesia in 1.5 per cent of the cases. The mortality rate in this series was 2.3 per cent; in 2 out of 3 cases death was of neurological origin; 21 per cent of the patients had peroperative neurological accidents which, in 9 out of 10 cases, were due to a low cerebral blood flow rate during clamping. Thirty-five intra-arterial shunts (8.9 per cent) were installed, and none of these accidents was permanent. Twenty-five patients (6.3 per cent) had postoperative deficit which did not regress in 12 cases (3 per cent). The risk of peroperative neurological accident was significantly increased in patients with bilateral lesions of the vertebral arteries (x 3.5) or with occlusion of the contralateral carotid artery (x 4.5). Surgery of the carotid artery in conscious patients reveals a high incidence of ischaemic neurological events the reversibility of which is ensured by appropriate therapeutic procedures (arterial shunt, increase of brain perfusion pressure). Patients at risk of neurological accidents may benefit from cervical extradural anaesthesia.

[The use of free forearm flaps in oropharyngeal neoplastic surgery. Our experience with 52 cases]. / Utilisation du lambeau libre antébrachial dans la chirurgie carcinologique oro-pharyngée. Notre expérience à propos de 52 cas.

The authors report their experience in the management of a series of 52 patients treated in Nantes for repair of loss of substance in the bucco-pharyngeal cavity, using a free antebrachial flap. Its fundamental value is to provide a very fine, supple cutaneous sheet of large surface area, which is particularly adapted to bucco-pharyngeal cancer surgery by limiting as much as possible the anatomical and functional sequelae and thereby allowing much larger resections to be carried out. After a review of the anatomy, a study of the indications, precautions and results obtained in this series is presented.

[Lateral cysts and fistulae of the neck. Apropos 70 cases]. / Kystes et fistules latéraux du cou. A propos de 70 cas.

Anomalies of branchial origin, amygdaloid cysts and fistulae of 1st, 2nd and 3rd slits are not rare cervical affections. Their histology is characteristic: cylindrical epithelium for fistulae and malpighian epithelium with lymphoid masses for cysts. Excision must be completed by an approach route that is sufficiently wide to avoid recurrence and vascular-neural lesions of the neck.

[Angiolymphoid hyperplasia with eosinophilia or Kimura's disease]. / L'hyperplasie angiolymphoïde avec éosinophilie ou maladie de Kimura.

A rare affection of unknown etiology that is benign but frequently recurrent, Kimura's disease involves infiltration of the dermis and hypodermis usually of the face. Documented data exists describing clinical findings and results of histopathology that are analogous but are grouped under other names: angiolymphoid hyperplasia with eosinophilia, pyogenic pseudogranuloma, atypical pyogenic granuloma. A case followed up for 13 years is reported.

[Schwannoma of the pterygomaxillary fossa, excision by transmandibular approach]. / Schwannome de la fosse ptérygo-maxillaire, exérèse par voie transmandibulaire.

Primary tumors of the pterygomaxillary fossa are rare and difficult to approach surgically. A case of a schwannoma is reported, extirpation being through a transmandibular approach using an osteotomy-osteosynthesis procedure.

[Conservation of the mandible by osteotomy-osteosynthesis in "trans-mandibular" oropharyngectomy. 34 case reports]. / La conservation de la mandibule par ostéotomie-ostéosynthèse dans lóro-pharyngectomie "trans-mandibulaire". A propos de 34 observations.

Trans-mandibular oropharyngectomy was performed in 34 patients, as initial treatment in 20 cases and following tumoral recurrence after radiotherapy in the other 14 cases. Results indicate that mandibular conservation is possible when bone is not affected by the neoplastic process and when an oropharyngoplasty ensures perfect covering of the mandible. The site of choice for osteotomy-osteosynthesis appears to be the parasymphysial region, as this provides a very satisfactory route of approach, the mental nerve and innervation of the lip are respected, it is situated outside of the irradiation field (before or after surgery), and there are no dental articulation complications.