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1.
Hernia ; 28(2): 485-494, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38177404

RESUMO

PURPOSE: The width of the Linea alba, which is often gauged by inter-rectus distance, is a key risk factor for incisional hernia and recurrence. Previous studies provided limited descriptions with no consideration for width, location variability, or curvature. We aimed to offer a comprehensive 3D anatomical analysis of the Linea alba, emphasizing its variations across diverse demographics. METHODS: Using open source software, 2D sagittal plane and 3D reconstructions were performed on 117 patients' CT scans. Linea alba length, curvature assessed by the sagitta (the longest perpendicular segment between xipho-pubic line and the Linea alba), and continuous width along the height were measured. RESULTS: The Linea alba had a rhombus shape, with a maximum width at the umbilicus of 4.4 ± 1.9 cm and a larger width above the umbilicus than below. Its length was 37.5 ± 3.6 cm, which increased with body mass index (BMI) (p < 0.001), and was shorter in women (p < 0.001). The sagitta was 2.6 ± 2.2 cm, three times higher in the obese group (p < 0.001), majorated with age (p = 0.009), but was independent of gender (p = 0.212). Linea alba width increased with both age and BMI (p < 0.001-p = 0.002), being notably wider in women halfway between the umbilicus and pubis (p = 0.007). CONCLUSION: This study provides an exhaustive 3D description of Linea alba's anatomical variability, presenting new considerations for curvature. This method provides a patient-specific anatomy description of the Linea alba. Further studies are needed to determine whether 3D reconstruction correlates with pathologies, such as hernias and diastasis recti.


Assuntos
Parede Abdominal , Hérnia Incisional , Humanos , Feminino , Herniorrafia , Parede Abdominal/diagnóstico por imagem , Parede Abdominal/cirurgia , Índice de Massa Corporal , Hérnia Incisional/cirurgia , Obesidade
2.
AIDS Behav ; 25(3): 689-698, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32910354

RESUMO

Driving ability can be diminished amongst people with HIV with associated neurocognitive impairment (NCI). We explore the relationship between HIV status, NCI and driving ability in professional truck drivers. Forty male professional drivers (20 HIV-positive; mean age = 39.20 ± 7.05) completed a neuropsychological test battery, two driving simulator tasks that assessed driving ability, and a driving history and habits questionnaire. A higher proportion of HIV-positive drivers exhibited impaired overall cognitive performance (p ≤ 0.001). Overall, drivers with NCI (defined as z ≤ 1.00) were more likely than those without NCI to crash (p = 0.002). There were no significant between-group (HIV-positive versus HIV-negative) differences with regard to self-reported on-road driving events. Professional drivers with NCI, as measured on a driving simulator, are at increased risk of making driving errors under high-risk conditions compared to their neurocognitively normal counterparts. These data should inform driver health management with regard to annual medical screening and surveillance.


RESUMEN: La capacidad de conducción puede verse disminuida entre las personas con VIH con deterioro neurocognitivo asociado (neurocognitive impairment, NCI). Exploramos la relación entre la situación frente al VIH, el NCI y la capacidad de conducción en conductores profesionales de camiones. Cuarenta conductores profesionales masculinos (20 seropositivos, edad media = 39.20 ± 7.05) completaron una batería de pruebas neuropsicológicas, dos tareas de simulador de conducción que evaluaron la capacidad de conducción y un cuestionario de hábitos y antecedentes de conducción. Una mayor proporción de conductores VIH positivos exhibió un desempeño cognitivo general deficiente (p ≤ 0.001). En general, los conductores con NCI (definido como z ≤ 1.00) tenían más probabilidades de chocar que aquellos sin NCI (p = 0.002). No hubo diferencias significativas entre los grupos (VIH positivo frente a VIH negativo) con respecto a los eventos autoinformados de conducción en carretera. Los conductores profesionales con NCI, según lo medido en un simulador de conducción, tienen un mayor riesgo de cometer errores de conducción en condiciones de alto riesgo en comparación con sus homólogos neurocognitivamente normales. Estos datos deberían informar a la gestión de la salud del conductor en lo que respecta a la vigilancia y los exámenes médicos anuales.


Assuntos
Condução de Veículo/estatística & dados numéricos , Infecções por HIV/complicações , Saúde Ocupacional , Acidentes de Trânsito , Adulto , Condução de Veículo/psicologia , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Destreza Motora , Veículos Automotores , Testes Neuropsicológicos , Inquéritos e Questionários
3.
Morphologie ; 102(337): 69-77, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29530649

RESUMO

Most osteolytic tumors are in fact mixed and contain an osteoblastic component associated with the predominant osteolytic areas. This metaplastic woven bone is always evidenced by histological analysis even in the absence of radiological expression. Metaplastic bone formation reflects the activation of new osteoblasts coming from the stimulation of the dormant lining cells. Twelve patients with secondary metastases of the iliac crest evidenced by hot spots on a 99Tc-MBP san were diagnosed by histomorphometry on bone biopsies. Fourier Transformed InfraRed analysis and Imaging (FTIRI) was used on 4µm thick sections of undecalcified bone. The mineralization degree, carbonate substitution, crystallinity and the cross-links ratio of collagen (1660/1690cm-1 bands) were determined. The matrix characteristics were analyzed and imaged in the pre-existing residual bone and in the metaplastic woven bone in the vicinity of the tumor cells. FTIRI provided images of the phosphate, amide and combination of peak ratio after having selected the peaks of interest. In addition, the matrix properties can be measured and compared between the old and newly-formed bones. Woven bone appeared poorly calcified with a low phosphate/amide ratio (P=0.03) crystallinity (P<0.0001) and carbonate substitution (P=0.003). Collagen was less mature as evidenced by lower cross-links (P=0.01). Woven bone associated with bone metastasis appears poorly mineralized and rapidly elaborated by osteoblasts. The collagenous phase of the bone matrix has a low level of reticulation. FTIRI is a powerful tool to measure and visualize the various components of the bone matrix in human diseases.


Assuntos
Densidade Óssea , Neoplasias Ósseas/diagnóstico por imagem , Ílio/diagnóstico por imagem , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Biópsia , Matriz Óssea/diagnóstico por imagem , Matriz Óssea/patologia , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Estudos de Viabilidade , Feminino , Humanos , Ílio/patologia , Masculino , Osteogênese , Estudos Retrospectivos , Medronato de Tecnécio Tc 99m/administração & dosagem
4.
Clin Genet ; 91(6): 868-880, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28229453

RESUMO

The group of chondrodysplasia with multiple dislocations includes several entities, characterized by short stature, dislocation of large joints, hand and/or vertebral anomalies. Other features, such as epiphyseal or metaphyseal changes, cleft palate, intellectual disability are also often part of the phenotype. In addition, several conditions with overlapping features are related to this group and broaden the spectrum. The majority of these disorders have been linked to pathogenic variants in genes encoding proteins implicated in the synthesis or sulfation of proteoglycans (PG). In a series of 30 patients with multiple dislocations, we have performed exome sequencing and subsequent targeted analysis of 15 genes, implicated in chondrodysplasia with multiple dislocations, and related conditions. We have identified causative pathogenic variants in 60% of patients (18/30); when a clinical diagnosis was suspected, this was molecularly confirmed in 53% of cases. Forty percent of patients remain without molecular etiology. Pathogenic variants in genes implicated in PG synthesis are of major importance in chondrodysplasia with multiple dislocations and related conditions. The combination of hand features, growth failure severity, radiological aspects of long bones and of vertebrae allowed discrimination among the different conditions. We propose key diagnostic clues to the clinician.


Assuntos
Deficiência Intelectual/genética , Anormalidades Musculoesqueléticas/genética , Osteocondrodisplasias/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Estudos de Associação Genética , Humanos , Lactente , Recém-Nascido , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/diagnóstico por imagem , Deficiência Intelectual/fisiopatologia , Masculino , Anormalidades Musculoesqueléticas/diagnóstico , Anormalidades Musculoesqueléticas/diagnóstico por imagem , Anormalidades Musculoesqueléticas/fisiopatologia , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/fisiopatologia , Radiografia , Sequenciamento do Exoma
5.
Neuroscience ; 277: 859-71, 2014 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-25090924

RESUMO

Current evidence suggests that inflammation plays a role in the pathophysiology of seizures. In line with this view, selected pro-inflammatory arachidonic acid derivatives have been reported to facilitate seizures. Kainate-induced seizures are accompanied by leukotriene formation, and are reduced by inhibitors of LOX/COX pathway. Moreover, LTD4 receptor blockade and LTD4 synthesis inhibition suppress pentylenetetrazol (PTZ)-induced kindling and pilocarpine-induced recurrent seizures. Although there is convincing evidence supporting that blood-brain-barrier (BBB) dysfunction facilitates seizures, no study has investigated whether the anticonvulsant effect of montelukast is associated with its ability to maintain BBB integrity. In this study we investigated whether montelukast and other CysLT receptor antagonists decrease PTZ-induced seizures, as well as whether these antagonists preserve BBB during PTZ-induced seizures. Adult male albino Swiss mice were stereotaxically implanted with a cannula into the right lateral ventricle, and two electrodes were placed over the parietal cortex along with a ground lead positioned over the nasal sinus for electroencephalography (EEG) recording. The effects of montelukast (0.03 or 0.3 µmol/1 µL, i.c.v.), pranlukast (1 or 3 µmol/1 µL, i.c.v.), Bay u-9773 (0.3, 3 or 30 nmol/1 µL, i.c.v.), in the presence or absence of the agonist LTD4 (0.2, 2, 6 or 20 pmol/1 µL, i.c.v.), on PTZ (1.8 µmol/2 µL)-induced seizures and BBB permeability disruption were determined. The animals were injected with the antagonists, agonist or vehicle 30 min before PTZ, and monitored for additional 30 min for the appearance of seizures by electrographic and behavioral methods. BBB permeability was assessed by sodium fluorescein method and by confocal microscopy for CD45 and IgG immunoreactivity. Bay-u9973 (3 and 30 nmol), montelukast (0.03 and 0.3 µmol) and pranlukast (1 and 3 µmol), increased the latency to generalized seizures and decreased the mean amplitude of EEG recordings during seizures. LTD4 (0.2 and 2 pmol) reverted the anticonvulsant effect of montelukast (0.3 µmol). Montelukast (0.03 and 0.3 µmol) prevented PTZ-induced BBB disruption, an effect that was reversed by LTD4 at the dose of 6 pmol, but not at the doses 0.2 and 2 pmol. Moreover, the doses of LTD4 (0.2 and 2 pmol) that reverted the effect of montelukast on seizures did not alter montelukast-induced protection of BBB, dissociating BBB protection and anticonvulsant activity. Confocal microscopy analysis revealed that 1. PTZ increased the number of CD45+ and double-immunofluorescence staining for CD45 and IgG cells in the cerebral cortex, indicating BBB leakage with leukocyte infiltration; 2. while LTD4 (6 pmol) potentiated, montelukast decreased the effect of PTZ on leukocyte migration and BBB, assessed by double-immunofluorescence staining for CD45 and IgG cells in the cannulated hemisphere. Our data do not allow us ruling out that mechanisms unrelated and related to BBB protection may co-exist, resulting in decreased seizure susceptibility by montelukast. Notwithstanding, they suggest that CysLT1 receptors may be a suitable target for anticonvulsant development.


Assuntos
Anticonvulsivantes/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Antagonistas de Leucotrienos/farmacologia , Fármacos Neuroprotetores/farmacologia , Convulsões/tratamento farmacológico , Acetatos/farmacologia , Animais , Barreira Hematoencefálica/fisiopatologia , Encéfalo/fisiopatologia , Permeabilidade Capilar/efeitos dos fármacos , Permeabilidade Capilar/fisiologia , Cromonas/farmacologia , Ciclopropanos , Relação Dose-Resposta a Droga , Imunoglobulina G/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Leucócitos/efeitos dos fármacos , Leucócitos/fisiologia , Leucotrieno D4/farmacologia , Masculino , Camundongos , Pentilenotetrazol , Quinolinas/farmacologia , Receptores de Leucotrienos/agonistas , Receptores de Leucotrienos/metabolismo , SRS-A/análogos & derivados , SRS-A/farmacologia , Convulsões/fisiopatologia , Sulfetos
6.
Morphologie ; 96(313): 40-3, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23022200

RESUMO

A 93 year-old woman with Paget's disease of bone had been treated with etidronate without interruption during 20 years. The daily dose was usual (5mg/kg/day) but this prescription had never been stopped by her physicians. Two fractures had already occurred in pagetic (right tibia) and non pagetic bones (right fibula) within the last 2 years, and she presented rib fractures, another right tibia fracture and right femur fracture during hospitalization time. X-rays films showed major osteolysis of left ulna and right tibia. Blood samples and technetium bone scan brought no evidence for sarcoma or lytic evolution of the disease. A transiliac bone biopsy on non pagetic bone site confirmed the diagnosis of osteomalacia (increased osteoid parameters), with secondary hyperparathyroidism (hook resorption). In Paget's disease of bone, continuous treatment by etidronate may induce generalized osteomalacia, and increase the risk of fracture in both pagetic and non-pagetic bones. Whereas physicians and pharmaceutical industry try to improve the observance of those drugs, this striking observation also points out that a prescription always needs to be updated.


Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Ácido Etidrônico/efeitos adversos , Fraturas Espontâneas/etiologia , Osteíte Deformante/tratamento farmacológico , Osteomalacia/induzido quimicamente , Idoso de 80 Anos ou mais , Fosfatase Alcalina/sangue , Biópsia , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Calcificação Fisiológica/efeitos dos fármacos , Carbonato de Cálcio/uso terapêutico , Colecalciferol/uso terapêutico , Ácido Etidrônico/administração & dosagem , Ácido Etidrônico/farmacologia , Ácido Etidrônico/uso terapêutico , Feminino , Fraturas do Fêmur/etiologia , Fíbula , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/induzido quimicamente , Doença Iatrogênica , Osteíte Deformante/complicações , Osteólise/sangue , Osteólise/induzido quimicamente , Osteólise/diagnóstico por imagem , Osteomalacia/sangue , Osteomalacia/tratamento farmacológico , Hormônio Paratireóideo/sangue , Cintilografia , Fraturas das Costelas/etiologia , Fraturas da Tíbia/etiologia , Ulna/patologia , Vitamina D/análogos & derivados , Vitamina D/sangue
7.
Mol Vis ; 14: 1912-28, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18958307

RESUMO

PURPOSE: Choroidal melanoma is the most common primary malignant ocular tumor in human adults. Relevant mouse models of human uveal melanoma still remain to be developed. We have studied the transgenic mouse strain, Tyrp-1-TAg, to try to gain insight into possible molecular mechanisms common to pigmented ocular neoplasms occurring spontaneously in the eyes of these mice and human choroidal melanoma. The role of two members of the ETS (E26 avian leukemia oncogene) family of transcription factors, ETS-1 and ETS-2, has been investigated in many cancers but has not yet been studied in ocular tumors. METHODS: This is the first study describing the production and distribution of ETS-1 and ETS-2 mRNAs and proteins using in situ hybridization and immunohistochemistry in murine ocular tissue sections of normal control eyes and tumoral eyes from mice of the same age. Using semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) and western blots experiments, we compared changes in ETS-1 and ETS-2 expression, their protein levels, and the regulation of some of their target gene expressions at different stages of the ocular tumoral progression in the transgenic mouse model, Tyrp-1-TAg, with those in normal eyes from control mice of the same age. RESULTS: In normal control adult mouse eyes, ETS-1 was mostly present in the nuclei of all neuroretinal layers whereas ETS-2 was mostly localized in the cytosol of the cell bodies of these layers with a smaller amount present in the nuclei. Both were found in the retinal pigmentary epithelium (RPE). ETS-1 and ETS-2 mRNA and protein levels were much higher in the ocular tissues of Tyrp-1-TAg mice than in control ocular tissues from wild-type mice. This upregulation was correlated with tumor progression. We also demonstrated upregulation of ETS-1 and ETS-2 target expressions in Tyrp-1-TAg mice when comparing with the same target expressions in control mice. CONCLUSIONS: Our findings suggest that ETS-1 and ETS-2 are upregulated in ocular tumors derived from the retinal epithelium and may be involved in one or several signaling pathways that activate the expression of a set of genes involved in ocular tumor progression such as those encoding ICAM-1 (intercellular adhesion molecule-1), PAI-1 (Plasminogen activator inhibitor-1), MCP-1 (monocyte chemoattractant protein-1) and p16 (Cyclin dependent kinase inhibitor 2A).


Assuntos
Neoplasias Oculares/genética , Regulação Neoplásica da Expressão Gênica , Pigmentação/genética , Proteína Proto-Oncogênica c-ets-1/genética , Proteína Proto-Oncogênica c-ets-2/genética , Regulação para Cima/genética , Animais , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Modelos Animais de Doenças , Olho/metabolismo , Olho/patologia , Neoplasias Oculares/metabolismo , Neoplasias Oculares/patologia , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Camundongos , Camundongos Transgênicos , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Transporte Proteico , Proteína Proto-Oncogênica c-ets-1/metabolismo , Proteína Proto-Oncogênica c-ets-2/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
8.
Ann Biol Clin (Paris) ; 66(2): 157-64, 2008.
Artigo em Francês | MEDLINE | ID: mdl-18390426

RESUMO

OBJECTIVES: to evaluate specificity and sensibility of the rheumatoid factors (RF), the anti-cyclic citrullinated peptide antibodies (CCP) and the anti-keratin antibodies (AKA) according to the rheumatoid arthritis (RA) diagnosis; pathology other than RA with at least one of these marker positive; the significance of the flocculent fluorescence of the antibodies AKA by indirect immunofluorescence (IIF). METHOD: two hundred forty height patients were studied: 121 RA, 89 inflammatory rheumatisms, 23 non inflammatory rheumatisms, and 15 non rheumatic affections. The RF was investigated by nephelometry, the anti-CCP by immunofluorometry and the AKA by IIF on rat oesophagus. RESULTS: specificity and sensibility were respectively in a retrospective manner: 68% and 83% for the RF, 95% and 76% for the anti- CCP, 83% and 40% for the AKA during RA with evolution of less than one year. The rates of agreements were: RF versus CCP: 81%, RF versus AKA: 57%, CCP versus AKA: 73%. Twelve patients with pathologies different from RA have positive anti-CCP or AKA. Thirty three of the patients with anti-CCP level superior to 130 U/mL have flocculent AKA versus only 5% when the anti-CCP are lower than 130 U/mL. CONCLUSION: the RF and the anti-CCP are complementary in RA. Autoimmune and neoplasic pathologies are sometimes responsible for the positivity of the anti-CCP and the AKA. The flocculent aspect of AKA in IIF may be associated with raised concentrations of anti-CCP.


Assuntos
Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Queratinas/imunologia , Peptídeos Cíclicos/imunologia , Fator Reumatoide/sangue , Biomarcadores , Interpretação Estatística de Dados , Ensaio de Imunoadsorção Enzimática , Testes de Floculação , Técnica Indireta de Fluorescência para Anticorpo , Seguimentos , Humanos , Estudos Multicêntricos como Assunto , Nefelometria e Turbidimetria , Estudos Retrospectivos , Sensibilidade e Especificidade , Fatores de Tempo
9.
AIDS Care ; 19(9): 1166-70, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18058401

RESUMO

This study evaluates putative individual- and contextual-level social risk factors that may influence the likelihood that Filipina female sex workers (FSWs) attend and utilize health services for STI screening. Face-to-face interviews were conducted with 1004 FSWs and their 86 employers. Research staff also collected clinic appointment attendance data. Hierarchical linear modelling was used to estimate the simultaneous effects of individual- and workplace-level factors. Results showed that both individual- and contextual-level characteristics were associated with STI screening appointment attendance. Individual characteristics found to have significant effects on clinic attendance included occupation, income, length of work and commercial sex involvement. City of establishment was a workplace characteristic significantly associated with appointment attendance. In addition to cross-level interactions, the impact of individual-level occupation depended upon characteristics of the workplace. These findings suggest that individual health service utilization is contingent upon contextual-level risk factors in the workplace. Intervention implications aimed at increasing clinic attendance are discussed.


Assuntos
Instituições de Assistência Ambulatorial/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Trabalho Sexual , Infecções Sexualmente Transmissíveis/diagnóstico , Adolescente , Adulto , Feminino , Humanos , Filipinas , Fatores de Risco
10.
Toxicol Lett ; 159(3): 203-11, 2005 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-16188404

RESUMO

Psychostimulant drugs abuse is associated with an increased risk of stroke. Cytochromes P450 (CYP), especially the astrocytic members of the CYP2C subfamily may play an important role in the modulation of cerebrovascular functions, by generating vasodilatator metabolites from arachidonic acid (AA). Our study examined the regulation of CYP2C genes in response to cocaine or amphetamine in the human astrocyte-like U373 MG cells, using reverse transcription-polymerase chain reaction (RT-PCR) and western-blot analysis. A treatment for 48h with increasing concentrations of cocaine caused a significant down-regulation of CYP2C8 and CYP2C9 genes and decreased the protein level. These effects were not observed with amphetamine. One mechanism of the CYP2C mRNA regulation implicates various specific receptors including glucocorticoid receptor (GR) and constitutive androstane receptor (CAR). Effects of cocaine on CYP2C were accompanied by a decrease in the GR and CAR gene expression suggesting that these nuclear receptors could be involved in the CYP2C repression by cocaine in the U373 MG cell line. These findings represent a possible molecular mechanism involved in the cerebrovascular risk associated with cocaine abuse.


Assuntos
Astrócitos/efeitos dos fármacos , Cocaína/toxicidade , Sistema Enzimático do Citocromo P-450/genética , Expressão Gênica/efeitos dos fármacos , Receptores Citoplasmáticos e Nucleares/genética , Receptores de Glucocorticoides/genética , Fatores de Transcrição/genética , Astrócitos/enzimologia , Astrócitos/metabolismo , Astrocitoma , Linhagem Celular Tumoral , Receptor Constitutivo de Androstano , Regulação para Baixo , Humanos
11.
Ann Rheum Dis ; 64(6): 913-20, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15550531

RESUMO

OBJECTIVE: To assess the tolerance and efficacy of rituximab in patients with various autoimmune diseases seen in daily rheumatological practice. METHODS: 866 rheumatology and internal medicine practitioners were contacted by e-mail to obtain the files of patients treated with rituximab for systemic autoimmune diseases. Patients with lymphoma were analysed if the evolution of the autoimmune disease could be evaluated. RESULTS: In all, 43 of 49 cases could be analysed, including 14 with rheumatoid arthritis (RA), 13 with systemic lupus erythematosus (SLE), six with primary Sjogren's syndrome (pSS), five with systemic vasculitis, and five with other autoimmune diseases. Rituximab was prescribed for lymphoma in two patients with RA and two with pSS. In the 39 other cases, rituximab was given because of the refractory character of the autoimmune disease. The mean follow up period was 8.3 months (range 2 to 26). There were 11 adverse events in 10 patients and treatment had to be discontinued in six. Efficacy was observed in 30 patients (70%): RA 11, SLE 9, pSS 5, vasculitis 2, antisynthetase syndromes 2, sarcoidosis 1. The mean decrease in corticosteroid intake was 9.5 mg/d (range 0 to 50) in responders. Seven patients experienced relapse after mean 8.1 months (5 to 15). Three patients died because of refractory autoimmune disease. CONCLUSIONS: Despite absence of marketing authorisation, rituximab is used to treat various refractory autoimmune diseases in daily rheumatological practice. This study showed good tolerance and short term clinical efficacy, with marked corticosteroid reduction in patients with SLE, pSS, vasculitis, and polymyositis.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Doenças Reumáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Murinos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Esquema de Medicação , Quimioterapia Combinada , Feminino , Glucocorticoides/administração & dosagem , Humanos , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab , Síndrome de Sjogren/tratamento farmacológico , Resultado do Tratamento , Vasculite/tratamento farmacológico
12.
Toxicol Lett ; 138(3): 243-51, 2003 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-12565201

RESUMO

The present work aims to determine the relevance of an astrocytoma cell line U373 MG, for assessing the role of some astroglial cytochrome P450 in neurotoxicity and neuroprotection. CYP1B1, CYP2C8, CYP2C9, CYP2D6, CYP2J2, CYP2E1 and CYP4A11 mRNA were detected by reverse transcriptase-polymerase chain reaction in control U373 MG cell cultures. Among them we focused on CYP1B1 expression. After 48 h treatment with a range of concentrations of interleukin-1beta (1, 5, 10 ng/ml) used to simulate stress conditions, CYP1B1 mRNA expression was enhanced in a dose-dependent way. This increased expression was followed 24 h later by an increase in protein level, determined by Western-blot. N-acetylcysteine (NAC) partially inhibited this effect both on the mRNA and protein levels. As CYP1B1 activates procarcinogenic compounds to reactive metabolites, an increase in this P450 isoform will participate to toxic consequences of an inflammatory/oxidative stress. NAC will prevent this deleterious effect.


Assuntos
Acetilcisteína/farmacologia , Hidrocarboneto de Aril Hidroxilases/metabolismo , Astrócitos/enzimologia , Interleucina-1/toxicidade , Estresse Oxidativo/imunologia , Hidrocarboneto de Aril Hidroxilases/genética , Hidrocarboneto de Aril Hidroxilases/imunologia , Astrócitos/efeitos dos fármacos , Astrócitos/imunologia , Astrocitoma , Citocromo P-450 CYP1B1 , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/imunologia , Citocromo P-450 CYP2D6/metabolismo , Interações Medicamentosas , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/imunologia , Humanos , Interleucina-1/antagonistas & inibidores , Isoenzimas/genética , Isoenzimas/imunologia , Isoenzimas/metabolismo , Microssomos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Regulação para Cima/imunologia
13.
Rev Neurol (Paris) ; 158(6-7): 728-30, 2002 Jul.
Artigo em Francês | MEDLINE | ID: mdl-12486903

RESUMO

We report the case of a patient presenting a sudden bilateral hearing loss. Four years before, a bladder carcinoma was resected and a chemotherapy was started. Gadolinium-enhanced magnetic resonance images revealed enhancement of both acoustic nerves. Cerebrospinal fluid analysis showed malignant cells consistent with the initial bladder cancer. Meningeal metastases from bladder carcinoma are extremely rare. Systemic chemotherapy and its low meningeal diffusion may enhance the incidence of this complication. Bilateral hearing loss is a rare initial manifestation of meningeal carcinomatosis.


Assuntos
Carcinoma/complicações , Carcinoma/diagnóstico , Perda Auditiva Bilateral/etiologia , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/diagnóstico , Antineoplásicos/uso terapêutico , Carcinoma/secundário , Nervo Coclear/patologia , Perda Auditiva Bilateral/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Meníngeas/secundário , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/líquido cefalorraquidiano , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia
15.
Presse Med ; 31(6): 244-8, 2002 Feb 16.
Artigo em Francês | MEDLINE | ID: mdl-11883365

RESUMO

THE ROLE OF IONIC CHANNEL DYSFUNCTION: During various neurological diseases has been evoked for many years on electro-physiological data. Molecular biology has led to great progress in neurology, and can be considered "functional" since it is surpasses the classical anatomo-clinical methods. IONIC CHANNEL DYSFUNCTION: Can be determined genetically, resulting from the mutation of a gene code of a channel sub-unit. CHANNELOPATHIES ARE RESPONSIBLE: For muscular diseases (myotonia, familial periodic paralysis, malignant hyperthermia and congenital myasthenia), but also for central nervous system disorders such as familial hemiplegic migraine, hereditary paroxystic ataxia and certain forms of Mendel's law hereditary epilepsy. ACQUIRED IONIC CHANNEL DYSFUNCTION: Resulting from auto-immune aggression is implied in diseases such as Lambert-Eaton's myasthenic syndrome and Isaac's neuromyotonia syndrome. It probably plays a part in the clinical, and particularly the sensitive expression (paresthesia and pain) of some peripheral neuropathies and certain central nervous system affections, such as multiple sclerosis.


Assuntos
Canais Iônicos , Doenças do Sistema Nervoso/fisiopatologia , Humanos , Dor/etiologia , Dor/fisiopatologia , Parestesia/etiologia , Parestesia/fisiopatologia
16.
J Gene Med ; 3(5): 478-87, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11601761

RESUMO

BACKGROUND: Colloidal stability of lipid/DNA aggregates is a major requirement for cationic lipid-mediated transfection which is particularly difficult to fulfil at the high DNA concentrations used for in vivo gene delivery. Thus, we have investigated the potential of poly(ethyleneglycol) (PEG) conjugates for steric stabilization of lipoplexes formed by bis(guanidinium)-tren-cholesterol/dioleoyl phosphatidylethanolamine (BGTC/DOPE) liposomes, a class of cationic liposomes we have developed over the past few years. METHODS AND RESULTS: We demonstrate that adequate lipophilic PEG derivatives can stabilize BGTC/DOPE lipoplexes formed at high DNA concentration. We also report the results of cryotransmission electron microscopy studies indicating that PEG-stabilized lipoplexes form DNA-coated structures which assemble into clusters exhibiting various complex morphologies. Finally, we report data from in vivo transfection experiments suggesting that PEG-mediated colloidal stabilization of concentrated lipoplex solutions may allow enhanced transfection of the mouse airways via intranasal administration. CONCLUSION: Our results represent an important step towards the design of multimodular BGTC-based systems for improved in vivo gene transfection.


Assuntos
Cloranfenicol/análogos & derivados , Colesterol/análogos & derivados , Colesterol/genética , Glicerofosfolipídeos/genética , Pulmão/metabolismo , Fosfatidiletanolaminas , Transfecção , Animais , Sobrevivência Celular , Cloranfenicol/metabolismo , Colesterol/química , Colesterol/metabolismo , DNA/química , DNA/ultraestrutura , Feminino , Técnicas de Transferência de Genes , Vetores Genéticos , Glicerofosfolipídeos/química , Glicerofosfolipídeos/metabolismo , Guanidinas/química , Guanidinas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Polietilenoglicóis/química , Células Tumorais Cultivadas
17.
Radiat Res ; 156(5 Pt 1): 535-44, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11604067

RESUMO

Ionizing radiation elicits a genetic response in human cells that allows cell survival. The human KIN (also known as KIN17) gene encodes a 45-kDa nuclear DNA-binding protein that participates in the response to UVC radiation and is immunologically related to the bacterial RecA protein. We report for the first time that ionizing radiation and bleomycin, a radiomimetic drug, which produce single- and double-strand breaks, increased expression of KIN in human cells established from tumors, including MeWo melanoma, MCF7 breast adenocarcinoma, and ATM+ GM3657 lymphoblast cells. KIN expression increased rapidly in a dose-dependent manner after irradiation. Under the same conditions, several genes controlled by TP53 were induced with kinetics similar to that of KIN. Using the CDKN1A gene as a marker of TP53 responsiveness, we analyzed the up-regulation of KIN and showed that is independent of the status of TP53 and ATM. In contrast, the presence of a dominant mutant for activating transcription factor 2 (ATF2) completely abolished the up-regulation of KIN. Our results suggest a role for ATF2 in the TP53-independent increase in KIN expression after gamma irradiation.


Assuntos
Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Proteínas Nucleares , Proteína Supressora de Tumor p53/fisiologia , Fator 2 Ativador da Transcrição , Bleomicina/farmacologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/fisiologia , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/genética , Dano ao DNA , Raios gama , Humanos , Proteínas de Ligação a RNA , Fatores de Transcrição/fisiologia , Células Tumorais Cultivadas
18.
Rev Med Interne ; 22(8): 745-8, 2001 Aug.
Artigo em Francês | MEDLINE | ID: mdl-11534360

RESUMO

INTRODUCTION: Papillary fibroelastoma is a benign cardiac tumor which can be associated with serious embolic complications. EXEGESIS: We report on a 42-year-old man admitted for an ischemic stroke in the left middle cerebral artery region. Transesophageal echocardiography revealed a mitral valve tumor. Surgical excision and histological examination showed a papillary fibroelastoma. Clinical course was uneventful. CONCLUSION: We consider the high embolic potential of this tumor, which represents a surgically treatable cause of ischemic stroke.


Assuntos
Isquemia Encefálica/etiologia , Infarto Cerebral/etiologia , Fibroelastose Endocárdica/complicações , Valva Mitral/patologia , Adulto , Ecocardiografia , Esôfago/diagnóstico por imagem , Humanos , Masculino , Artéria Cerebral Média/patologia , Valva Mitral/diagnóstico por imagem
19.
Presse Med ; 30(9): 411-6, 2001 Mar 10.
Artigo em Francês | MEDLINE | ID: mdl-11285778

RESUMO

DEFINITION: Inflammatory cranial hypertrophic pachymeningitis (ICHP) is a fibrosing inflammatory process that thickens the dura mater. This condition is increasingly reported owing to the use of CT and MRI. CLINICAL ASPECTS: Chronic headache and cranial neuropathies are the main presentations. Generally the erythrocyte sedimentation rate is elevated and cerebrospinal fluid is inflammatory. DIAGNOSIS: Non-invasive imagery visualizes the thickening of the dura mater that may be focal or diffuse. On MRI diffuse intense enhancement due to intra cranial hypotension must not be confused with ICHP. Focal thickening of the dura may be tumoral. Biopsy of the thickened dura mater is useful for confirming the inflammatory nature of the process and for orienting the etiological diagnosis. "SECONDARY" ICHP: ICHP has many causes, infectious and noninfectious. It may be the presenting manifestation of systemic diseases as sarcoïdosis or Wegener's granulomatosis. "IDIOPATHIC" ICHP: A diagnosis of exclusion, ICHP might be an isolated intracranial localization of multifocal fibrosis, an ill-defined autoimmune disease. TREATMENT: A specific treatment is indicated in some cases of secondary ICHP. In most cases treatment relies on corticosteroids an/or immunosuppressive therapy.


Assuntos
Meningite/diagnóstico , Corticosteroides/uso terapêutico , Dura-Máter/patologia , Humanos , Hipertrofia , Imunossupressores/uso terapêutico , Imageamento por Ressonância Magnética , Meningite/tratamento farmacológico , Meningite/etiologia , Tomografia Computadorizada por Raios X
20.
J Subst Abuse Treat ; 20(2): 121-7, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11306214

RESUMO

We examined the occurrence of violent traumatic events, DSM-III-R diagnosis of posttraumatic stress disorder (PTSD), and PTSD symptoms, and the relationship of these variables to drug abuse severity. One-hundred fifty opioid-dependent drug abusers who were participants in a randomized trial of two methadone treatment interventions were interviewed using the Diagnostic Interview Schedule, the Addiction Severity Index, and the Beck Depression Inventory. Twenty-nine percent met diagnostic criteria for PTSD. With the exception of rape, no gender differences in the prevalence of violent traumatic events were observed. The occurrence of PTSD-related symptoms was associated with greater drug abuse severity after controlling for gender, depression, and lifetime diagnosis of PTSD. The high rate of PTSD among these methadone patients, the nature of the traumatic events to which they are exposed, and subsequent violence-related psychiatric sequelae have important implications for identification and treatment of PTSD among those seeking drug abuse treatment.


Assuntos
Dependência de Heroína/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Violência/psicologia , Adulto , Terapia Combinada , Comorbidade , Diagnóstico Duplo (Psiquiatria) , Feminino , Dependência de Heroína/diagnóstico , Dependência de Heroína/reabilitação , Humanos , Masculino , Metadona/uso terapêutico , Pessoa de Meia-Idade , Terapia Socioambiental , Transtornos de Estresse Pós-Traumáticos/diagnóstico
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