[Pharmaceutical system of fecal microbiota transplantation: Heterogeneous practices]. / Circuit pharmaceutique, transplantation de microbiote fécal : Des pratiques hétérogènes.

OBJECTIVE: To describe current pharmaceutical practice in French hospitals regarding fecal microbiota transplantation in terms of prescription, preparation and compounding, as well as local legislation. MATERIAL AND METHODS: A national survey was conducted at 28 French university hospital centers followed by the sending of a GoogleForm® questionnaire from June to August 2018 in the 16 respondent centers either performing or subcontracting fecal microbiota transplant. RESULTS: All hospitals performing or subcontracting fecal transplant (n=16,%57) report prescription indication of recurrent Clostridium difficile infection treatment, and 6 of them also as part of a clinical trial protocol. In hospitals performing fecal transplant themselves (n=11), the number of pre-donation consultations with donors varies from one (n=6) to two (n=5). Fecal sample is collected at the donor's home in 45% of cases. Route of administration for transplant is either naso-gastric administration (n=4), rectal (n=4) or both (n=5). Fecal samples for transplant are compounded either in the hospital pharmacy (n=73%) or in the laboratory (27%). Thawing methods include refrigeration between 2-8°C (50%), room temperature (25%) and water bath (25%). Billing system and reporting to health authorities are highly heterogeneous from one hospital to another. CONCLUSION: This survey shows significant pharmaceutical practice heterogeneity within French hospitals regarding fecal microbiota transplantation despite the existence of national and European recommendations.

Hypochlorous acid is antipruritic and anti-inflammatory in a mouse model of atopic dermatitis.

BACKGROUND: It has been reported that topical hypochlorous acid (HOCl) formulations lead to relief of itch in human patients with atopic dermatitis; however, the specific antipruritic mechanism of action remains unclear. OBJECTIVE: To confirm itch relief and reduction of lesions in a mouse model of atopic dermatitis and to elucidate possible HOCl's mode of action. METHODS: In this study, the effects of topical administration of HOCl hydrogel (0.05%) on atopic dermatitis-like lesions in NC/Nga mice model as well as in vitro effects of HOCl on dorsal root ganglia neurons and mouse bone marrow-derived dendritic cells (mBMDCs) were investigated. NC/Nga mice were sensitized with house dust mite allergen and treated topically with HOCl hydrogel both preventively and therapeutically against established lesions. Allergen challenge was continued during HOCl hydrogel application. RESULTS: Treatment with HOCl hydrogel prevented the development of lesions and scratching bouts during the whole observation period. When administered after full development of lesions, HOCl reduced lesions and scratching behaviour to a similar extent as a positive control 0.1% betamethasone dipropionate ointment. The reduced inflammatory response by HOCl treatment was demonstrated by reduced secretion of inflammatory cytokines in affected skin tissue from NC/Nga mice. In addition, HOCl significantly reduced IL-12 production in mBMDC. The diminished scratching behaviour was confirmed by impaired response to several pruritogens in dorsal root ganglia neurons excised from NC/Nga mice after termination of the studies. The response to the stimuli was also reduced by pre-incubation of sensory neurons from untreated BALB/c mice with 0.0001% HOCl. CONCLUSIONS AND CLINICAL RELEVANCE: These data indicate a direct reduction in sensory response by HOCl, leading to significantly reduced itch and inflammation in vivo.

The immunoglobulin superfamily member CD200R identifies cells involved in type 2 immune responses.

BACKGROUND: The pathology of allergic diseases involves type 2 immune cells, such as Th2, ILC2, and basophils exerting their effect by production of IL-4, IL-5, and IL-13. However, surface receptors that are specifically expressed on type 2 immune cells are less well documented. The aim of this investigation was to identify surface markers associated with type 2 inflammation. METHODS: Naïve human CD4+ T cells were short-term activated in the presence or absence of IL-4 and analyzed for expression of >300 cell-surface proteins. Ex vivo-isolated peripheral blood mononuclear cells (PBMCs) from peanut-allergic (PA) and nonallergic subjects were stimulated (14-16 h) with peanut extract to detect peanut-specific CD4+ CD154+ T cells. Biopsies were obtained for transcriptomic analysis from healthy controls and patients with extrinsic or intrinsic atopic dermatitis (AD) and psoriasis. RESULTS: Expression analysis of >300 surface proteins enabled identification of IL-4-upregulated surface proteins, such as CD90, CD108, CD109, and CD200R (CD200R1). Additional analysis of in vitro-differentiated Th0, Th1, and Th2 cultures identified CD200R as upregulated on Th2 cells. From ex vivo-isolated PBMCs, we found high expression of CD200R on Th2 and ILC2 cells and basophils. In PA subjects, the peanut-specific Th2 (CD154+ CRTh2+ ) cells expressed more CD200R than the non-allergen-specific Th2 (CD154- CRTh2+ ) cells. Moreover, costaining of CD161 and CD200R identified peanut-specific highly differentiated IL-4+ IL-5+ Th2 cells. Finally, transcriptomic analysis revealed upregulation of CD200R in lesional skin from subjects with an extrinsic AD phenotype compared to healthy skin. CONCLUSION: These results indicate that CD200R expression strongly correlates with Th2 pathology; though, the mechanism is as yet elusive.

Human Atopic Dermatitis Skin-derived T Cells can Induce a Reaction in Mouse Keratinocytes in vivo.

In atopic dermatitis (AD), the inflammatory response between skin-infiltrating T cells and keratinocytes is fundamental to the development of chronic lesional eczema. The aim of this study was to investigate whether skin-derived T cells from AD patients could induce an inflammatory response in mice through keratinocyte activation and consequently cause the development of eczematous lesions. Punch biopsies of the lesional skin from AD patients were used to establish skin-derived T cell cultures, which were transferred to NOD.Cg-Prkd(scid) Il2rg(tm1Sug) /JicTac (NOG) mice. We found that the subcutaneous injection of the human AD skin-derived T cells resulted in the migration of the human T cells from subcutis to the papillary dermis followed by the development of erythema and oedema in the mouse skin. Furthermore, the human T cells induced a transient proliferative response in the mouse keratinocytes shown as increased numbers of Ki-67(+) keratinocytes and increased epidermal thickness. Out of six established AD skin-derived T cell cultures, two were superior at inducing a skin reaction in the mice, and these cultures were found to contain >10% CCR10(+) T cells compared to <2% for the other cultures. In comparison, blood-derived in vitro-differentiated Th2 cells only induced a weak response in a few of the mice. Thus, we conclude that human AD skin-derived T cells can induce a reaction in the mouse skin through the induction of a proliferative response in the mouse keratinocytes.

Secular trends of hip fractures in Québec, Canada.

UNLABELLED: This study examined the secular trends of hip fracture incidence among individuals 50 years and older in Québec between 1993 and 2004. Age-standardized rates decreased at both the provincial and regional levels. The largest relative decrease was observed among younger females, and rates declined more slowly in the elderly. INTRODUCTION: The population of the province of Québec is among the oldest in North America. Before the trend rupture reported in the late 1990s in several countries, hip fracture (HF) incidence rates did not show a secular trend (between 1981 and 1992). This study examined the secular trends of HF incidence at the provincial level and in two of the most important urban areas of the province, Montréal and Québec City, between 1993 and 2004. METHODS: All hospitalisations of individuals 50 years and older living in the province of Québec between 1993 and 2004 with a main diagnosis of HF were included. Standardized rates of HF incidence were calculated for females and males, 50-74 years and 75 years and older. RESULTS: The Québec City area showed a strong decreasing trend in HF rates for younger females, but the other groups did not show an obvious trend. Although our models did not support the existence of significant differences in trends between both areas, the rates of HF of younger males and, to a lesser extent, of older women in the Montréal area were significantly higher than in the Québec City area. CONCLUSIONS: Differences observed in hip fracture rates as well as in secular trends between age groups and gender emphasise the need for decision makers to rely on results based on age-specific and sex-specific analyses.

Safety, healing, and efficacy of vascular prostheses coated with hydroxypropyl-ß-cyclodextrin polymer: experimental in vitro and animal studies.

OBJECTIVES: Polyester vascular prostheses (PVPs) coated with a polymer of hydroxypropyl-ß-cyclodextrin (HPßCD) have been designed to provide an in situ reservoir for the sustained delivery of one or more bioactive molecules. The goal of this study was to assess the efficacy, the safety and the healing properties of these prostheses. METHODS: Collagen-sealed PVPs were coated with the HPßCD-based-polymer (PVP-CD) using the pad-dry-cure textile finishing method and loaded with one or two antibiotics. Appropriate control and PVP-CD samples were tested in several in vitro and animal model conditions. The study end points included haemolysis, platelet aggregation, antibacterial efficacy, polymer biodegradation, acute toxicity and chronic tolerance. RESULTS: PVP-CD proved to be compatible with human blood, since it did not induce haemolysis nor influenced ADP-mediated platelet aggregation. Sustained antimicrobial efficacy was achieved up to 7 days against susceptible bacteria when PVP-CDs were loaded with the appropriate drugs. Analysis of harvested PVP-CD from the animal model revealed that the HPßCD-based coating was still present at 1 month but had completely disappeared 6 months after implantation. All grafts were patent, well encapsulated without healing abnormalities. Clinical data, blood-sample analysis and histological examination did not evidence any signs of acute or chronic, local or systemic toxicity in the animal models. CONCLUSION: PVP-CD was proved safe and demonstrated excellent biocompatibility, healing and degradation properties. Effective antimicrobial activity was achieved with PVP-CD in conditions consistent with a sustained-release mechanism.

Designed sponges based on chitosan and cyclodextrin polymer for a local release of ciprofloxacin in diabetic foot infections.

Diabetic foot infections are the most common complications requiring hospitalisation of patients with diabetes. They often result in amputation to extremities and are associated with high morbi-mortality rates, especially when bone is infected. Treatment of these complications is based on surgical procedures, nursing care and systemic antibiotic therapy for several weeks, with a significant risk of relapse. Due to low blood flow and damage caused by diabetic foot infection, blood supply is decreased, causing low antibiotic diffusion in the infected site and an increase of possible bacterial resistance, making this type of infection particularly difficult to treat. In this context, the aim of this work was to develop a medical device for local antibiotic release. The device is a lyophilized physical hydrogel, i.e a sponge based on two oppositely charged polyelectrolytes (chitosan and poly(cyclodextrin citrate)). Cyclodextrins, via inclusion complexes, increase drug bioavailability and allow an extended release. Using local release administration increases concentrations in the wound without risk of toxicity to the body and prevents the emergence of resistant bacteria. The hydrogel was characterised by rheology. After freeze-drying, a curing process was implemented. The swelling rate and cell viability were evaluated, and finally, the sponge was impregnated with a ciprofloxacin solution to evaluate its drug release profile and its antibacterial activity.

Chemical, biological and microbiological evaluation of cyclodextrin finished polyamide inguinal meshes.

This study describes the use of cyclodextrins (CDs) as a finishing agent of polyamide (PA) fibers used in order to obtain inguinal meshes with improved antibiotic delivery properties. The finishing process involved polymerization between citric acid and CDs, which yielded a cross-linked polymer that physically adhered to the surface of PA fibers. This permanent functionalization was characterized by evaluating the damping property with a polar liquid (glycerol) via the drop contact angle method for various rates of modification of the fabrics. The biological and microbiological effects of the PA, which were functionalized with hydroxypropylated derivate of gamma-CD (HP-gamma-CDs) and charged with ciprofloxacin (CFX), were evaluated by cell culture assays. We observed a good adhesion and proliferation of fibroblastic cells (NIH3T3) after 3 and 6 days and no detectable toxicity of the modified substrate. The in vitro antibacterial activity of the HP-gamma-CD grafted PA fabrics charged with CFX against the bacteria Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli was greatly superior to that of the virgin sample within a 24h batch experiment in human blood plasma medium. In conclusion, these results from our study offer an insight into the efficient performance of CDs as drug delivery systems for multiple applications in the fields of biomaterials and medical textiles.

Computational Study of the Binding Modes of Diverse DPN Analogues on Estrogen Receptors (ER) and the Biological Evaluation of a New Potential Antiestrogenic Ligand.

Estrogen (17ß-estradiol) is essential for normal growth and differentiation in the mammary gland. In the last three decades, previous investigations have revealed that Estrogen Receptor Alpha (ERα) plays a critical role in breast cancer. More recently, observations regarding the widespread expression of ERß-like proteins in normal and neoplastic mammary tissues have suggested that ERß is also involved in the mentioned pathology. Design of new drugs both steroidal and nonsteroidal that target any of these receptors represents a promise to treat breast cancer although it remains a challenge due to the sequence similarity between their catalytic domains. In this work, we propose a new set of compounds that could effectively target the estrogen receptors ERα and ERß. These ligands were designed based on the chemical structure of the ERß-selective agonist Diarylpropionitrile (DPN). The designed ligands were submitted to in silico ADMET studies, yielding in a filtered list of ligands that showed better drug-like properties. Molecular dynamics simulations of both estrogen receptors and docking analysis were carried-out employing the designed compounds, from which two were chosen due to their promising characteristics retrieved from theoretical results (docking analysis or targeting receptor predictions). They were chemically synthetized and during the process, two precursor ligands were also obtained. These four ligands were subjected to biological studies from which it could be detected that compound mol60b dislplayed inhibitory activity and its ability to activate the transcription via an estrogenic mechanism of action was also determined. Interestinly, this observation can be related to theoretical binding free energy calculations, where the complex: ERß-mol60b showed the highest energy ΔGbind value in comparison to others.

Respiratory rhythms generated in the lamprey rhombencephalon.

Brainstem networks generating the respiratory rhythm in lampreys are still not fully characterized. In this study, we described the patterns of respiratory activities and we identified the general location of underlying neural networks. In a semi-intact preparation including the brain and gills, rhythmic discharges were recorded bilaterally with surface electrodes placed over the vagal motoneurons. The main respiratory output driving rhythmic gill movements consisted of short bursts (40.9+/-15.6 ms) of discharge occurring at a frequency of 1.0+/-0.3 Hz. This fast pattern was interrupted by long bursts (506.3+/-174.6 ms) recurring with an average period of 37.4+/-24.9 s. After isolating the brainstem by cutting all cranial nerves, the frequency of the short respiratory bursts did not change significantly, but the slow pattern was less frequent. Local injections of a glutamate agonist (AMPA) and antagonists (6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or D,L-amino-5-phosphonopentanoic acid (AP5)) were made over different brainstem regions to influence respiratory output. The results were similar in the semi-intact and isolated-brainstem preparations. Unilateral injection of AP5 or CNQX over a rostral rhombencephalic region, lateral to the rostral pole of the trigeminal motor nucleus, decreased the frequency of the fast respiratory rhythm bilaterally or stopped it altogether. Injection of AMPA at the same site increased the rate of the fast respiratory rhythm and decreased the frequency of the slow pattern. The activity recorded in this area was synchronous with that recorded over the vagal motoneurons. After a complete transverse lesion of the brainstem caudal to the trigeminal motor nucleus, the fast rhythm was confined to the rostral area, while only the slow activity persisted in the vagal motoneurons. Our results support the hypothesis that normal breathing depends on the activity of neurons located in the rostral rhombencephalon in lampreys, whereas the caudal rhombencephalon generates the slow pattern.

Vascular prostheses with controlled release of antibiotics Part 2. In vitro biological evaluation of vascular prostheses treated by cyclodextrins.

Viability tests by the colony forming method show no toxicity for all CDs (beta-CD, gamma-CD, HPbeta-CD and HPgamma-CD) and their associated polymer. A survival rate of 100% is observed for all CDs at high concentration 400 ppm. Proliferation tests revealed a low proliferation of L132 cells on grafted vascular prostheses and untreated prostheses and good proliferation on Melinex (film form of PET). A proliferation of 17% is observed after 3 days of incubation and decrease at 4% after 6 days on prostheses. Melinex exhibits a proliferation rate as the controls. Vitality tests confirm proliferation tests and show a good vitality of cells even for low cell amounts. From these experiments it becomes obvious that the decreasing proliferation rate is not a cytotoxic effect but is due to the chemical and/or physical surface characteristics. A similar result is obtained for cell adhesion kinetics between grafted vascular prostheses and control. After 2 h adhesion, a lower adhesion is observed on untreated prostheses. Theses results were confirmed by immunochemistry and morphology tests. This cell adhesion inhibiting effect of the PET prostheses contributes to a better "survival" of vascular prostheses without secondary obstruction or stenosis.

Vascular prostheses with controlled release of antibiotics Part 1: Surface modification with cyclodextrins of PET prostheses.

Vascular prostheses were functionalised with the aim to obtain a slow release of antibiotics in order to reduce postoperative infections. The original process that we present in this paper is based on the use of a family of cage molecules named cyclodextrins (CD). These compounds have the ability to form reversible inclusion complexes with drugs such as antibiotics. The aim of this work was to graft CD onto the prosthesis, so that an antibiotic can be bound on it by this inclusion phenomenon, and then be progressively released over a prolonged period by a complex dissociation mechanism. This paper presents the first part of this research program and concerns mainly the study of the functionalization parameters. It presents surface characterization results of the modified prostheses. The PET prostheses were immersed into a solution containing a cross linking agent, cyclodextrins (beta-CD, gamma-CD, HP-beta-CD and HP-gamma-CD) and a catalyst and were padded. Grafting occurred by the mean of a thermofixation step at a temperature comprised between 140 and 180 degrees C. It was observed that the support was permanently modified when the CD polymer that coated the fibres resisted to the final washing process. Grafting rates of 12 wt% in CD polymer could be reached. It was also observed that the fibre coating reaction induced an increase of the permeability of the grafts.

Functionalization of PVDF membranes with carbohydrate derivates for the controlled delivery of chlorhexidin.

Maltodextrin (MX) was fixed onto PVDF membranes in order to create a drug delivery Guided Tissue Regeneration (GTR) device with controlled drug delivery properties. PVDF microporous membranes were treated by a mixture of MX and citric acid, resulting to an 18 wt% increase of the supports. MX grafted membrane could capture 103 mg/g chlorhexidin digluconate (DigCHX) instead of 1mg/g for a virgin membrane. A neutralization step was performed before the biological tests. Viability tests confirmed the non-toxicity of the MX polymer coating after neutralisation. In vitro release test in human plasma, and microbiological tests showed that membranes grafted with MX were more performing compared to virgin and beta-CD grafted membranes. The antimicrobial activity was effective during more than 72 h.

Cyclodextrin modified PLLA parietal reinforcement implant with prolonged antibacterial activity.

The use of textile meshes in hernia repair is widespread in visceral surgery. Though, mesh infection is a complication that may prolong the patient recovery period and consequently presents an impact on public health economy. Such concern can be avoided thanks to a local and extended antibiotic release on the operative site. In recent developments, poly-l-lactic acid (PLLA) has been used in complement of polyethyleneterephthalate (Dacron®) (PET) or polypropylene (PP) yarns in the manufacture of semi-resorbable parietal implants. The goal of the present study consisted in assigning drug reservoir properties and prolonged antibacterial effect to a 100% PLLA knit through its functionalization with a cyclodextrin polymer (polyCD) and activation with ciprofloxacin. The study focused i) on the control of degree of polyCD functionalization of the PLLA support and on its physical and biological characterization by Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC) and cell viability, ii) on the understanding of drug/meshes interaction using mathematic model and iii) on the correlation between drug release studies in phosphate buffer saline (PBS) and microbiological evaluation of meshes and release medium against E. coli and S. aureus. All above mentioned tests highlighted the contribution of polyCD on the improved performances of the resulting antibacterial implantable material. STATEMENT OF SIGNIFICANCE: 1. We managed for the first time, with well-defined parameters in terms of temperature and time of treatment, to functionalize a bio-absorbable synthetic material to improve drug sorption and drug release properties without affecting its mechanical properties. 2. We analyzed for the first time the degradation of our coating products by mass spectroscopy to show that only citrate and cyclodextrin residues (and glucose units) without any cytotoxicity are formed. 3. We managed to improve the mechanical properties of the PLA with the cyclodextrin polymer to form a composite. The assembly (cyclodextrin polymer and PLLA) remains biodegradable.

Improved drug delivery properties of PVDF membranes functionalized with beta-cyclodextrin--application to guided tissue regeneration in periodontology.

The purpose of this study was to develop a membrane for guided tissue regeneration applicable in periodontology that could release antimicrobial agent during the healing period. Our strategy consisted to graft beta-cyclodextrin (beta-CD), a molecule that is known to form inclusion complexes with a large variety of drugs, onto PVDF membranes. Grafting occurred by using citric acid that provoked a crosslinking reaction of beta-CD, and the resulting polymer was imprisoned into the porous structure of the PVDF membrane. The reaction produced a weight increase of the membrane, the range of which depended on the temperature and on the time of curing applied in the process. The biological behavior of the membranes evaluated by proliferation and vitality tests showed good proliferation and improved activity of L132 epithelial cells on the raw and on the grafted membranes. Doxycyclin (DOX) and chlorhexidine (CHX) were used as antimicrobial agents. Their inclusion into the beta-CD cavity in aqueous solutions was confirmed by NMR spectroscopy. After the impregnation of the membranes with DOX and CHX, their release was studied in vitro in batch type experiments and measured by UV spectrophotometry. Low amounts of DOX and CHX were delivered from the raw membranes within the first few hours of tests. Grafted membranes, however, delivered DOX and CHX in larger quantities within 24 h and 10 days respectively.

Effect of different carboxylic acids in cyclodextrin functionalization of cellulose nanocrystals for prolonged release of carvacrol.

Current investigations deal with new surface functionalization strategy of nanocrystalline cellulose-based substrates to impart active molecule release properties. In this study, cellulose nanocrystals (CNC) were surface-functionalized with ß-cyclodextrin (ß-CD) using succinic acid (SA) and fumaric acid (FA) as bridging agents. The main objective of this surface modification performed only in aqueous media was to obtain new active materials able to release antibacterial molecules over a prolonged period of time. The reactions were conducted by immersing the CNC film into a solution composed of ß-CD, SA and FA, leading to CNC grafting. The materials were characterized by infrared spectroscopy (FT-IR), Quartz crystal microbalance-dissipation (QCM-D), AFM and phenolphthalein (PhP) was used to determine the efficiency of CNC grafting with ß-CD. The results indicated that ß-CD was successfully attached to the CNC backbone through the formation of ester bonds. Furthermore, carvacrol was entrapped by the attached ß-CD and a prolonged release was confirmed. In particular, CNC grafted to ß-CD in the presence of FA was selected as the best solution. The antibacterial activity and the controlled release were studied for this sample. Considerably longer bacterial activity against B. subtilis was observed for CNC grafted to ß-CD compared to CNC and CNC-FA, confirming the promising impact of the present strategy.

Andrews thoracoplasty as a treatment of post-pneumonectomy empyema: experience in 23 cases.

BACKGROUND: Andrew's thoracopleuroplasty has been described for treating tuberculous empyemas with bronchopleural fistulas. We report on its utilization for treating postpneumonectomy empyemas. METHODS: During a 25 year period, 23 patients underwent thoracopleuroplasty for treating postpneumonectomy empyemas, after a period of drainage-irrigation of the cavity. Seven patients presented with persistent bronchial fistula at operation. After resection of the costal arches surrounding the infected cavity, the cavity was cleaned, and the external parietal plane was sutured to the mediastinal plane. Only drainage of the subscapular space was left in place. RESULTS: Postoperative mortality was 4.3%. Postoperative recovery was simple in 17 cases, whereas a superficial abscess was evacuated in 3 cases. The procedure failed in 3 cases, which were treated by open thoracostomy (2), and by reenlargment of the thoracopleuroplasty (1). The sequelae were mainly a diminution of the shoulder mobility, especially when the first rib was resected. CONCLUSIONS: Thoracopleuroplasty may safely treat postpneumonectomy empyemas, even those with bronchial fistulas. Most patients are definitively and rapidly cured with limited sequelae.

[Acute carotid occlusion: thrombolytic treatment]. / Occlusion carotidienne aiguë: traitement par thrombolyse.

The occurrence of a neurologic deficit at the time of an acute obstruction of the internal carotid does not equate with neurons death. The size of the residual infarct depend on the duration and the depth of ischemia. The goal of fibrinolytic therapy is to obtain a fast reperfusin of the ischemic areas to limit the size of the residual infarct. The risk of reperfusion depend on the depth of the blood-brain barrier ischemia. The indications of reperfusion in emergency settings are based on pretherapeutic CTscan and angiographic assessment with cerebral digitalized parenchymography. Between 1984 and 1994, 100 ischemic strokes have been treated on emergency by local intra-arterial thrombolysis. The results depend on the condition of lenticulostriate arteries: --when the lenticulostriate arteries are not involved in the occlusion, arterial thrombolysis is very efficient (75% good results; 0% bad results) and has been performed up to the 12th hour. --when the lenticulostriate arteries are involved, the results are not as good (58% good results; 23% bad results); the hemorrhagic risk has dramatically dropped in this group when the decision was taken to do not treat the patients after the 5th hour (16.7% to 2.3%). There has been 7 deaths, 6 were due to non efficient revascularization of the parenchyma with vasogenic oedema. In conclusion, we think that ischemic stroke is an emergency; the cerebral digitalized parenchymography appears to be a major diagnostic and prognostic tool; intra-arterial thrombolysis is a very efficient technique when used at the right site and time.

[HBME-1 immunostaining in thyroid pathology]. / Intérêt de l'HBME-1 en pathologie thyroïdienne.

The aim of this study was to evaluate wether HBME-1 immunohistochemical analysis can reliably differentiate benign thyroid lesions from thyroid carcinomas. Fifty benign and 87 malignant lesions were analyzed. All papillary carcinomas (67/67) were HBME-1 positive, as well as 14 of 20 follicular well-differentiated carcinomas and 13 of 29 atypical follicular adenomas and 4 out of 21 goiters were weakly and focally positive. HBME-1 highlighted micronests of papillary carcinomas. The reactivity of HBME-1 in the tall-cell variant of papillary carcinomas was apical and stronger than in classical papillary carcinomas. Positive HBME-1 immunostaining is in support of the diagnosis of the follicular variant of papillary carcinoma and highlights micropapillary carcinomas. HBME-1 may be of additional value in the diagnosis of thyroid malignancy.