RESUMO
Epilepsy is one of the leading neurological diseases in both adults and children and in spite of advancement in medical treatment, 20 to 30% of patients remain refractory to current medical treatment. Medically intractable epilepsy has a real impact on a patient's quality of life, neurologic morbidity and even mortality. Actual therapy options are an increase in drug dosage, radiosurgery, resective surgery and non-resective neuromodulatory treatments (deep brain stimulation, vagus nerve stimulation). Resective, thermoablative or neuromodulatory surgery in the treatment of epilepsy are invasive procedures, sometimes requiring long stay-in for the patients, risks of permanent neurological deficit, general anesthesia and other potential surgery-related complications such as a hemorrhage or an infection. Radiosurgical approaches can trigger radiation necrosis, brain oedema and transient worsening of epilepsy. With technology-driven developments and pursuit of minimally invasive neurosurgery, transcranial MR-guided focused ultrasound has become a valuable treatment for neurological diseases. In this critical review, we aim to give the reader a better understanding of current advancement for ultrasound in the treatment of epilepsy. By outlining the current understanding gained from both preclinical and clinical studies, this article explores the different mechanisms and potential applications (thermoablation, blood brain barrier disruption for drug delivery, neuromodulation and cortical stimulation) of high and low intensity ultrasound and compares the various possibilities available to patients with intractable epilepsy. Technical limitations of therapeutic ultrasound for epilepsy surgery are also detailed and discussed.
Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Radiocirurgia , Terapia por Ultrassom , Adulto , Criança , Humanos , Qualidade de Vida , Epilepsia/cirurgiaRESUMO
Medulloblastoma is a cerebellar grade IV tumour according to the WHO classification, mainly seen in children under the age of 15. This cancer can nevertheless occur in adults. We report the case of a 22-year-old patient with a medulloblastoma disseminated in the spine. The patient had a type 1 Arnold-Chiari malformation causing hydrocephalus treated by ventriculoperitoneal shunt. The current condition began with perineal and lower limb hypoesthesia, ataxic gait, erectile dysfunction and urinary incontinence. Subsequently, a predominant paraparesis of the right lower limb appeared. The patient was treated according to the PNET HR+5 protocol combining two courses of conventional chemotherapy followed by two courses of high-dose chemotherapy with autograft recovery. Given the excellent response, a proton therapy was then delivered to the whole cerebrospinal axis with boosts to the primary tumour sites. The case of this young adult patient shows on the one hand an atypical presentation, and on the other hand underlines, in the absence of a specific therapeutic strategy established for adults, the importance of collaboration between the adult and pediatric oncology departments, with management integrating innovations such as proton therapy and molecular typing.
Le médulloblastome est une tumeur cérébelleuse de grade IV selon l'Organisation Mondiale de la Santé, principalement observée chez les enfants de moins de 15 ans. Ce cancer peut néanmoins survenir chez l'adulte. Nous rapportons le cas d'un patient de 22 ans présentant un médulloblastome disséminé au niveau du rachis. Le patient est porteur d'une malformation d'Arnold-Chiari de type 1 provoquant une hydrocéphalie traitée par dérivation ventriculo-péritonéale. L'affection actuelle a débuté par une hypoesthésie du périnée et des membres inférieurs, une démarche ataxique, un trouble érectile et des troubles vésico-sphinctériens. Par la suite est apparue une paraparésie prédominant au membre inférieur droit. Le patient a été traité selon le protocole pédiatrique PNET HR+5 combinant deux cures de chimiothérapie conventionnelle suivies de deux cures de chimiothérapie à haute dose avec rattrapage par autogreffe. Vu l'excellente réponse, une protonthérapie a été administrée sur l'axe cérébrospinal avec surdosages sur les sites primaires de la tumeur. Le cas de ce jeune adulte illustre, d'une part, une présentation atypique et d'autre part, souligne, en l'absence de stratégie thérapeutique spécifique établie pour l'adulte, l'importance de la collaboration entre les services d'Oncologie adulte et pédiatrique, la prise en charge intégrant les innovations telles que la protonthérapie et le typage moléculaire.
Assuntos
Neoplasias Cerebelares , Meduloblastoma , Adulto , Neoplasias Cerebelares/tratamento farmacológico , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/cirurgia , Criança , Humanos , Masculino , Meduloblastoma/tratamento farmacológico , Meduloblastoma/terapia , Adulto JovemRESUMO
INTRODUCTION: Moulds and mite allergens present in indoor environments are well known for their effects on respiratory health. METHODS: From 2011 to 2015, the Paris Service for Environmental Health (SPSE) conducted investigations in 293 dwellings following medical referral. These audits included fungal analysis of air (in 12% of dwellings), in mattress surface and floor dust (24%), and mite allergen quantifications in mattresses and carpets (18%). RESULTS: Indoor air fungal concentrations are not significantly different from those in outdoor air. When there is no ventilation or when the system is malfunctioning, an increase in indoor/outdoor air ratios is observed, indicating mould enrichment in the dwelling's indoor air. With regard to house dust samples, fungal spore concentrations vary according to the media from which samples were collected. Mattress fungal contamination is higher in dwellings where observed surface moulds exceed 1 per square meter. In the same way Der p1 mite allergens levels are greater in mattress dust in dwellings where mould contamination is visible. CONCLUSIONS: This study describes the levels of contamination in the dwellings of Parisian patients.
Assuntos
Poluição do Ar em Ambientes Fechados/análise , Alérgenos/análise , Exposição Ambiental/análise , Fungos/isolamento & purificação , Ácaros , Poluição do Ar em Ambientes Fechados/estatística & dados numéricos , Alérgenos/efeitos adversos , Animais , Antígenos de Dermatophagoides/análise , Poeira/análise , Exposição Ambiental/estatística & dados numéricos , Fungos/classificação , Fungos/imunologia , Humanos , Ácaros/citologia , Ácaros/imunologia , Paris/epidemiologia , Características de Residência/estatística & dados numéricosRESUMO
Mutations in the DAX1 gene cause X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HHG). In affected boys, primary adrenal insufficiency occurs soon after birth or during early childhood; HHG is recognized at the expected time of puberty. In this report, we describe the novel phenotype of a man who presented with apparently isolated adrenal insufficiency at 28 years of age. Examination revealed partial pubertal development and undiagnosed incomplete HHG. Gonadotropin therapy did not improve his marked oligospermia, suggesting a concomitant primary testicular abnormality. Genomic analysis revealed a novel missense mutation, I439S, in DAX1. The mutant DAX-1 protein was studied for its ability to function as a transcriptional repressor of target genes. Consistent with the patient's mild clinical phenotype, the I439S mutation conferred intermediate levels of repressor activity of DAX-1 when compared with mutations associated with classic AHC. This unique case extends the clinical spectrum of AHC to include delayed-onset primary adrenal insufficiency in adulthood and milder forms of HHG. Furthermore, in accordance with findings in Ahch (Dax1) knockout mice, the clinical features in this patient suggest that DAX-1 function is required for spermatogenesis in humans, independent of its known effects on gonadotropin production.
Assuntos
Glândulas Suprarrenais/fisiopatologia , Proteínas de Ligação a DNA/genética , Hipogonadismo/genética , Mutação , Receptores do Ácido Retinoico/genética , Proteínas Repressoras , Fatores de Transcrição/genética , Adulto , Idade de Início , Animais , Receptor Nuclear Órfão DAX-1 , Humanos , Hipogonadismo/fisiopatologia , Masculino , Camundongos , Camundongos KnockoutRESUMO
INTRODUCTION: To study the impact of the constant and inevitable inhalation of moulds, it is necessary to sample, identify and count the spores. BACKGROUND: Environmental sampling methods can be separated into three categories: surface sampling is easy to perform but non quantitative, air sampling is easy to calibrate but provides time limited information, and dust sampling which is more representative of long term exposure to moulds. The sampling strategy depends on the objectives (evaluation of the risk of exposure for individuals; quantification of the household contamination; evaluation of the efficacy of remediation). The mould colonies obtained in culture are identified using microscopy, Maldi-TOF, and/or DNA sequencing. VIEWPOINTS: Electrostatic dust collectors are an alternative to older methods for identifying and quantifying household mould spores. They are easy to use and relatively cheap. Colony counting should be progressively replaced by quantitative real-time PCR, which is already validated, while waiting for more standardised high throughput sequencing methods for assessment of mould contamination without technical bias. CONCLUSION: Despite some technical recommendations for obtaining reliable and comparable results, the huge diversity of environmental moulds, the variable quantity of spores inhaled and the association with other allergens (mites, plants) make the evaluation of their impact on human health difficult. Hence there is a need for reliable and generally applicable quantitative methods.
Assuntos
Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental/métodos , Fungos/isolamento & purificação , Tipagem Molecular/métodos , Técnicas de Tipagem Micológica/métodos , Alérgenos/análise , Animais , Poeira/análise , Fungos/classificação , Fungos/genética , HumanosRESUMO
Vertebral angiomas are frequent and often asymptomatic. Sometimes although they do not seem invasive radiologically, they are responsible for local pain. If there is concordance between pain and vertebral angioma localisation, surgery such as vertebroplasty or cyphoplasty can be proposed. These techniques lead to a quick and complete removal of symptoms.
Assuntos
Hemangioma/cirurgia , Procedimentos Ortopédicos/métodos , Neoplasias da Coluna Vertebral/cirurgia , Vértebras Torácicas/cirurgia , Feminino , Hemangioma/diagnóstico , Humanos , Pessoa de Meia-Idade , Dor/etiologia , Dor/cirurgia , Neoplasias da Coluna Vertebral/diagnósticoRESUMO
We have shown previously that two flavonoids, apigenin and tangeretin, enhance gap junctional intercellular communication (GJIC) in rat liver epithelial cells, named REL cells. Here, we show that these two flavones also antagonize the inhibition of GJIC induced by tumor promoters like 12-O-tetradecanoyl-phorbol-acetate (TPA) and 3,5,di-tertio-butyl-4-hydroxytoluene (BHT). Their preventive effect is rapid. It does not seem to involve any change of the amount of the connexin expressed in REL cells, connexin 43 (Cx 43), and in its phosphorylation state. Other flavonoids tested including naringenin, myricetin, catechin and chrysin did not enhance GJIC nor counteract TPA-induced inhibition of GJIC.
Assuntos
Carcinógenos/antagonistas & inibidores , Flavonas , Flavonoides/farmacologia , Fígado/efeitos dos fármacos , Óleos Voláteis/farmacologia , Animais , Western Blotting , Hidroxitolueno Butilado/farmacologia , Células Cultivadas , Camomila , Conexina 43/metabolismo , Dimetil Sulfóxido/farmacologia , Epitélio/efeitos dos fármacos , Imunofluorescência , Junções Comunicantes/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Plantas Medicinais , Ratos , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
Recently, Panoutsakopoulos et al. (1999) reported 2 cases of aneurysmal bone cysts with a recurrent (16;17)(q22;p13) translocation. We present here two additional cases harboring the same translocation as well as additional chromosomal changes.
Assuntos
Cistos Ósseos Aneurismáticos/genética , Aberrações Cromossômicas/genética , Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 17/genética , Translocação Genética , Cistos Ósseos Aneurismáticos/diagnóstico , Criança , Pré-Escolar , Bandeamento Cromossômico , Transtornos Cromossômicos , Feminino , Humanos , CariotipagemRESUMO
Tuberculosis remains a health problem in many developed countries. After the development of a sedimentation method, a semi-quantitative approach for bioaerosol monitoring of Mycobacterium tuberculosis based on polymerase chain reaction (PCR) was adapted for direct detection in air. Bovine serum albumin was added to override airborne environmental particle PCR inhibitors. The method gave positive results in hospital rooms where tubercular pneumonia patients were hospitalized during the first days after their diagnosis.
Assuntos
Microbiologia do Ar , Monitoramento Ambiental/métodos , Controle de Infecções/métodos , Mycobacterium tuberculosis/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/prevenção & controleRESUMO
A 31-year-old overweight man, suffering from high-blood pressure, was hospitalized for transient fits and hemiparesis. MRI disclosed a large irregular mass affecting the vault, meninges and invading the parietal lobe. At neurosurgery, the lesion was necrotic, hemorrhagic and poorly demarcated from the surrounding brain. Histopathology revealed a benign Langerhans cell histiocytosis. No other systemic nor organic lesions could be discovered. After additional local radiotherapy, the patient recovered completely and regained normal activities 6 months later.
Assuntos
Encéfalo/patologia , Histiocitose de Células de Langerhans/patologia , Adulto , Seguimentos , Histiocitose de Células de Langerhans/cirurgia , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
Mould exposure in indoor environments can cause various health effects: infections, allergies, toxic effects and irritations. We have lead environmental audits (n = 32), at physician's request, in suspected mould allergic patient homes. A deep home visit allows the detection of potential indoor fungal and humidity sources, afterwards, a sample strategy is determinate. Results show that indoor airborne spores concentrations vary from some units (CFU) to more than thousands per m3. In dust samples, the number of spores per gram ranges from hundred to millions. A statistical analysis shows that "mouldy dwellings" are more contaminated than "non mouldy" ones and than outdoor air. Mould species relative presence is specific in each contaminated home, depending on various factors (mouldy support nature, competition between species...).
Assuntos
Monitoramento Ambiental , Hipersensibilidade Respiratória/epidemiologia , Ar , Poeira , Monitoramento Ambiental/estatística & dados numéricos , Monitoramento Epidemiológico , Fungos/isolamento & purificação , Habitação , Humanos , Umidade , Paris , Hipersensibilidade Respiratória/etiologia , Especificidade da Espécie , Esporos FúngicosRESUMO
During the 2003 season, a second pollen collector has been established in Paris city (Audubon site) to study the representativeness of the initial collector situated on the roof of the Pasteur Institute. The Hygiene Laboratory of Paris followed the pollen counts from the two collectors, during the period going from May to September. Both the samplers are Lanzoni model with a flow rate of 10 l x min(-1). The quantitative results show that no statistical difference exists between the pollen counts obtained from the 2 sites (Mann-Withney test, p > .05). The dominant species are Urticaceae, Poacae and Castenea species for the 2 collectors. Their counts are similar except for Poacae whose results are higher at the Audubon site. The collection period do not take into account the pollen production period of many trees species because of the late installation of the collector on the Audubon site. The results show that the two sites chosen for the study of pollen distribution are comparable. Nevertheless, the comparative study should be maintained on the next year to get more details about the observed differences and to collect the early trees pollen.
Assuntos
Ar/análise , Monitoramento Ambiental/estatística & dados numéricos , Pólen , Ambrosia , Artemisia , Monitoramento Ambiental/instrumentação , Geografia , Paris , Poaceae , Pólen/classificação , Árvores , Saúde da População Urbana , UrticaceaeAssuntos
Antiparkinsonianos/uso terapêutico , Hematoma Subdural Agudo/complicações , Levodopa/uso terapêutico , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/etiologia , Adulto , Feminino , Hematoma Subdural Agudo/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Transtornos Parkinsonianos/patologia , Tomografia Computadorizada por Raios X/métodosRESUMO
A 16-year old male presented with a mediastinal germ cell tumor (seminoma) treated by combined surgery, radiotherapy and chemotherapy. Nine years later, he presented with an intracerebral germ cell tumor affecting both the suprasellar ventricles and the pineal area. After partial removal of the intraventricular tumor, the patient received radiotherapy and chemotherapy. No metastases could be found. He died 8 months later, probably from secondary cardiovascular disturbances. This case seems to be the first one to illustrate the possibility of multifocal extragonadal seminoma.
Assuntos
Neoplasias Encefálicas/patologia , Neoplasias do Mediastino/patologia , Seminoma/patologia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Terapia Combinada , Evolução Fatal , Humanos , Masculino , Neoplasias do Mediastino/terapia , Seminoma/secundário , Seminoma/terapiaRESUMO
Two flavones, apigenin and tangeretin, were studied for their ability to modulate gap junctional intercellular communication (GJIC) in the rat liver epithelial cell line REL. Their cytotoxicity was first determined by cell density and neutral red uptake assays: neither apigenin nor tangeretin are cytotoxic at 10 and 25 microM, the concentrations used in our experiments. We then studied GJIC using the dye transfer assay and we observed that both apigenin and tangeretin enhance it, the maximum stimulation (x 1.7-1.8) being achieved at 25 microM for 24 h. When the dye transfer was enhanced, the amount of connexin 43 increased, which was demonstrated by Western blot and immunofluorescence analysis. For apigenin only, Northern blot analysis showed an accumulation of connexin 43 mRNA. In addition, the incubation of REL cells with the two compounds, for 1 or 24 h, prevented the inhibition of dye transfer by 12-O-tetradecanoylphorbol-13-acetate (1 or 10 ng/ml). The enhancement of GJIC by apigenin could be one of the major mechanisms responsible for apigenin's anti-tumour promoting action in vivo. As for tangeretin, its capacity to enhance GJIC completes its potential protective properties towards the post-initiation process.
Assuntos
Comunicação Celular/efeitos dos fármacos , Flavonas , Flavonoides/farmacologia , Junções Comunicantes/efeitos dos fármacos , Fígado/citologia , Fígado/efeitos dos fármacos , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Animais , Células Cultivadas , Camomila , Conexina 43/efeitos dos fármacos , Conexina 43/genética , Conexina 43/fisiologia , Células Epiteliais , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Fígado/metabolismo , Vermelho Neutro/farmacocinética , Plantas Medicinais , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , Ratos , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
Gap junction intercellular communication (GJIC) plays an essential role in the control of growth, differentiation, and functions of different tissues. The expression of connexins (Cxs), the structural proteins of gap junctions, is developmentally regulated and tissue-specific. In vivo hepatocytes express Cx32 and Cx26. Most currently available in vitro hepatic cell systems express Cx43 instead of the expected Cxs. This work analyzes the GJIC competence and Cx expression of the highly differentiated and polarized hepatoma-derived hybrid cell lines, WIF 12-1 and WIF-B. It shows (using two dye transfer assays) that both lines communicate efficiently and that the acquisition of GJIC competence precedes the formation of bile canaliculi. Interestingly, these cells communicate via Cx32 expression, whereas Cx26 and Cx43 are not expressed, as demonstrated by Western and Northern blotting, immunocytochemistry, and confocal microscopy. The human fibroblast W138 parent communicates via Cx43, whereas the rat hepatoma parent Fao and the subclone WIF 12-1 TGdelta, that has lost the human X chromosome, do not communicate, the expression of Cx32 being restricted to the mRNA in these two lines. The GJIC competence of WIF cells could thus result from the activation of the human X chromosome-linked Cx32 gene.
Assuntos
Comunicação Celular/fisiologia , Polaridade Celular/fisiologia , Conexinas/metabolismo , Junções Comunicantes/fisiologia , Células Híbridas/fisiologia , Fígado/citologia , Animais , Canalículos Biliares/fisiologia , Carcinoma Hepatocelular/patologia , Conexina 26 , Humanos , Ratos , Células Tumorais Cultivadas , Proteína beta-1 de Junções ComunicantesRESUMO
The mechanism by which all-trans retinoic acid (RA) stimulates gap junctional intercellular communication (GJIC) in the rat liver epithelial cell line. IAR203, was investigated. When RA, at 0.1 microM for 24-48 h, enhanced the dye transfer in IAR203 cells (x 1.4), it increased the amount of connexin43 (Cx43) in the cell-cell contact regions of the plasma membrane, as evidenced by analysis by Western blot and by immunofluorescence. It had no effect on the level of Cx43 mRNA. Freeze-fracture analysis of the size of gap junctions revealed an increase of the proportion of small gap junctions in RA-treated cells. We conclude that, in IAR203 cells, RA stimulates GJIC by acting at the post-transcriptional level of Cx43 regulation. The possibility that RA acts indirectly on the regulation of Cx43 expression, and increases the half-life of Cx43 by inducing adhesion molecules is discussed.
Assuntos
Conexina 43/biossíntese , Fígado/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Tretinoína/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Western Blotting , Linhagem Celular , Corantes , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Imunofluorescência , Técnica de Fratura por Congelamento , Junções Comunicantes/efeitos dos fármacos , Meia-Vida , Fígado/citologia , Fígado/metabolismo , Biossíntese de Proteínas/efeitos dos fármacos , RNA Mensageiro/metabolismo , RatosRESUMO
BACKGROUND: Activation of the p21ras and pp60c-src oncoproteins occurred at high incidence in the early stage of human colorectal carcinogenesis. Our study aimed to investigate the role of these signal-transduction pathways in the process of initiation and promotion of the malignant phenotype in intestinal cells. METHODS: The human Ha-ras and the polyoma middle T (Py-MT) viral oncogenes were transferred into large T oncogene of simian virus 40 immortalized rat intestinal epithelial SLC-44 cells and human colonic adenocarcinoma Caco-2 cells. RESULTS: These transfers conferred the tumorigenic and invasive phenotypes on immortalized SLC-44 cells and potentiated the tumorigenicity of Caco-2 cells and markedly repressed the terminal differentiation of this cell line. In SLC-44T cells, induction of the invasive phenotype by the activated Ha-ras oncogene correlated with weak expression of E-cadherin and reduced accumulation of the transcripts encoding the basement membrane components alpha 1 (IV) collagen, nidogen, and BM40, which might result partly from the inactivation of the transforming growth factor beta signaling pathway. The down-regulation of the alpha 1 (IV) collagen messenger RNA in SLC-44T cells was not due to the protein kinase C-dependent pathways or the secretion of autocrine factor(s). CONCLUSIONS: These results suggest that the activation of the p21ras and Py-MT/pp60c-src oncogenic pathways are critical effectors at different stages of colorectal carcinogenesis and in Caco-2 cells interferes with the program of enterocyte differentiation.