RESUMO
Viruses represent a driving force in the evolution of microorganisms including those thriving in extreme environments. However, our knowledge of the viral diversity associated to microorganisms inhabiting the deep-sea hydrothermal vents remains limited. The phylum of Thermotogae, including thermophilic bacteria, is well represented in this environment. Only one virus was described in this phylum, MPV1 carried by Marinitoga piezophila. In this study, we report on the functional and genomic characterization of two new bacterioviruses that infect bacteria from the Marinitoga genus. Marinitoga camini virus 1 and 2 (MCV1 and MCV2) are temperate siphoviruses with a linear dsDNA genome of 53.4 kb and 50.5 kb respectively. Here, we present a comparative genomic analysis of the MCV1 and MCV2 viral genomes with that of MPV1. The results indicate that even if the host strains come from geographically distant sites, their genomes share numerous similarities. Interestingly, heavy metals did not induce viral production, instead the host of MCV1 produced membrane vesicles. This study highlights interaction of mobile genetic elements (MGE) with their hosts and the importance of including hosts-MGEs' relationships in ecological studies.
Assuntos
Bactérias Anaeróbias/virologia , Bacteriófagos/isolamento & purificação , Microbiologia da Água , Archaea , Bacteriófagos/classificação , Bacteriófagos/genética , Genoma Viral , Fontes Hidrotermais/microbiologia , Filogenia , Água do Mar/microbiologiaRESUMO
PURPOSE: Sentinel-lymph-node (SLN) resection seems to minimize systematic axillary-lymph-node dissection (sALND) side effects in operated breast cancer patients. We explored whether SLN resection achieves similar therapeutic outcomes as sALND but with fewer side effects. METHODS: A randomized, controlled, open-label trial with parallel-group design compared sALND restricted to cases with positive SLN biopsy (test arm, n = 774) versus SLN biopsy followed by sALND (control arm, n = 770). RESULTS: The five-year overall survivals in control and test arms were 96.42 and 95.64% (P = 0.2925). The estimated difference was nearly zero (precisely, - 0.79%, one-tailed 95% confidence interval (CI) limit - 2.44%). In a multivariate Cox model, the adjusted hazard ratio in the test arm was HR 0.81 (upper 95% CI limit 1.17). Advanced age (HR 1.05 per additional year, CI [1.03-1.08]), negative progesterone receptor (HR 2.17 [1.35-3.45]), SLN metastasis (HR 1.69 [1.03-2.79]), and only one SLN identification technique (HR 4.14 [1.21-14.18]) were associated with lower survival. Patients with ≥ 1 severe side effect at 1 month in control and test arms were 173/703 = 24.6% [21.5-28.0%] and 91/693 = 13.1% [10.7-15.9%] (P < 0.001). The estimated sensitivity of SLN biopsy (control arm) was 145/178 = 81.5% [74.8-86.7%]. CONCLUSIONS: Restricting ALND to cases with positive SLN biopsy does not affect the overall survival but reduces by 11.5% [7.5-15.6%] (P < 0.001) the risk of severe short-time side effects of sALND.
Assuntos
Axila/patologia , Neoplasias da Mama/diagnóstico , Linfonodo Sentinela/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Feminino , Humanos , Metástase Linfática , Mastectomia/efeitos adversos , Mastectomia/métodos , Complicações Pós-Operatórias , Prognóstico , Modelos de Riscos Proporcionais , Biópsia de Linfonodo SentinelaRESUMO
Closely related sympatric species commonly develop different ecological strategies to avoid competition. Ctenomys minutus and C. flamarioni are subterranean rodents parapatrically distributed in the southern Brazilian coastal plain, showing a narrow sympatric zone. To gain understanding on food preferences and possible competition for food resources, we evaluated their diet composition performing DNA metabarcoding analyzes of 67 C. minutus and 100 C. flamarioni scat samples, collected along the species geographical ranges. Thirteen plant families, mainly represented by Poaceae, Araliaceae, Asteraceae and Fabaceae, were identified in the diet of C. minutus. For C. flamarioni, 10 families were recovered, with a predominance of Poaceae, Araliaceae and Asteraceae. A significant correlation between diet composition and geographical distance was detected in C. minutus, whereas the diet of C. flamarioni was quite homogeneous throughout its geographical distribution. No significant differences were observed between males and females of each species. However, differences in diet composition between species were evident according to multivariate analysis. Our results suggest some level of diet partitioning between C. flamarioni and C. minutus in the sympatric region. While the first species is more specialized on few plant items, the second showed a more varied and heterogeneous diet pattern among individuals. These differences might have been developed to avoid competition in the region of co-occurrence. Resource availability in the environment also seems to influence food choices. Our data indicate that C. minutus and C. flamarioni are generalist species, but that some preference for Poaceae, Asteraceae and Araliaceae families can be suggested for both rodents.
Assuntos
Código de Barras de DNA Taxonômico/métodos , Dieta/veterinária , Roedores/fisiologia , Simpatria , Animais , Brasil , Ecossistema , Feminino , Geografia , Masculino , Plantas/genética , Especificidade da EspécieRESUMO
STUDY DESIGN: Interventions using virtual feedback (VF) impact on motor functions and pain and may be relevant for neurorehabilitation after spinal cord injury (SCI) in which motor dysfunctions and (concomitant) pain are frequently observed. Potential mechanisms underlying VF include a modulation of cortical sensorimotor integration, increased therapy engagement and distraction from effort and pain. Still, the optimal parameters for VF and their technical implementation are currently unknown. OBJECTIVES: To provide an overview of interventions that have used VF to improve motor functions or to reduce pain after SCI. METHODS: Literature review. RESULTS: A total number of 17 studies were identified. VF interventions commonly focused on improving motor functions (n=12) or reducing pain (n=4). Only one study assessed both motor functions and pain. Studies generally report beneficial effects. However, the evidence is of low-level quality and many practical as well as theoretical issues remain unclear. Remaining knowledge gaps include: (1) optimal VF system characteristics, (2) the impact of different VF modalities and tasks, (3) dose-response relationships and (4) the identification of patients that are likely to benefit from VF. Future work should start by closing these knowledge gaps using systematic and controlled multi-session interventions and by assessing the underlying mechanisms involved. CONCLUSION: These results provide an important incentive to further assess the potential of VF interventions to simultaneously improve motor functions and reduce pain after SCI, which could contribute to better neurorehabilitation outcomes after SCI.
Assuntos
Biorretroalimentação Psicológica/métodos , Transtornos dos Movimentos/reabilitação , Dor/reabilitação , Traumatismos da Medula Espinal/reabilitação , Interface Usuário-Computador , Humanos , Transtornos dos Movimentos/etiologia , Dor/etiologia , Manejo da Dor , Traumatismos da Medula Espinal/complicações , Resultado do TratamentoRESUMO
Voice and speech impairments are frequent in Parkinson's disease, particularly when the disease is at an advanced stage. These impairments affect spoken communication and may become a serious disability for someone with Parkinson's disease. Many studies based on auditory-perceptual or acoustic methods have been carried out to characterize dysarthria. The heterogeneity of evaluation methods and experimental bias however make results difficult to understand. For instance, in terms of phonatory impairments and with regard to F0, results are contradictory: PD speech may be characterized by either higher F0 or lower F0 compared to control subjects, or there may be no difference at all between the two population. In this study, we aim to provide a conceptual and methodological framework which allows for interpreting the results obtained from 44 speakers (29 PD and 15 control subjects) in relation to physiological (gender, age, PD subjects' pharmacologic state) and linguistic (speech production tasks) constraints. For the present corpus, we did not observe any F0 mean difference between the two groups. Our results however reveal a significant increase in F0 mean in PD subjects under L-dopa. We assume a double and opposite effect on F0 mean during drug withdrawal: low sub-glottal pressure, due to PD, results in a decrease in F0, while laryngeal rigidity leads to an increase in F0. These two effects thus mutually annihilate. Under L-Dopa, however, the drug effect increases sub-glottal pressure, which combined with an increase in F0 due to rigidity, leads to a global increase in F0.
Assuntos
Dopaminérgicos/uso terapêutico , Levodopa/uso terapêutico , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Fonação/efeitos dos fármacos , Distúrbios da Fala/tratamento farmacológico , Distúrbios da Fala/etiologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Doença de Parkinson/fisiopatologia , Acústica da Fala , Distúrbios da Fala/fisiopatologia , Resultado do TratamentoRESUMO
AIMS: Escherichia coli is able to reduce azo compounds such as methyl red (MR) and nitro compounds such as 7-nitrocoumarin-3-carboxylic acid (7NCCA). The aim of this study was to clarify the specificity of the major E. coli reductases. METHODS AND RESULTS: Enzymatic assays with pure enzymes obtained after cloning, overproduction and purification under native or denaturing conditions were performed on three enzymes: AzoR, NfsA and NfsB. Their dependence on putative cofactors such as flavin mononucleotide (FMN), NADH and NADPH was studied as well as the reductase capacity of E. coli mutants depleted for one, two or three of the corresponding genes. CONCLUSIONS: AzoR was able to reduce both MR and 7NCCA, whereas NfsA and NfsB could only reduce the nitro compound. AzoR and NfsB were strictly FMN dependent in contrast to NfsA. At a low oxygen concentration, the three proteins were not mandatory for azo reduction and nitro reduction, but in optimal aerobic conditions, azoR was essential for MR reduction, and an nfsA/nfsB combination was important for 7NCCA reduction. Overexpression of azoR gene was able to compensate for the loss of nfsA and nfsB under aerobic conditions. SIGNIFICANCE AND IMPACT OF STUDY: These data provide new insights into the substrate specificity of major E. coli nitroreductases and demonstrate that oxygen is an important parameter to take into account in studies of nitroreductase activity.
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Proteínas de Escherichia coli/metabolismo , Escherichia coli/enzimologia , NADH NADPH Oxirredutases/metabolismo , Nitrorredutases/metabolismo , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Proteínas de Escherichia coli/genética , Mononucleotídeo de Flavina/metabolismo , NADH NADPH Oxirredutases/genética , Nitrorredutases/genética , Especificidade por SubstratoAssuntos
ADP-Ribosil Ciclase 1 , Antígenos CD34 , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/metabolismo , Antígenos Comuns de Leucócito , Glicoproteínas de Membrana , Mieloma Múltiplo , Adulto , Autoenxertos , Feminino , Células-Tronco Hematopoéticas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapiaRESUMO
Many situations can be considered as a crisis in radiotherapy (failure of equipment, absenteeism, excessive workload, errors, urgent care, pandemic, etc.). Such events are defined as difficult situations in the course of daily activity, they can at any time escape the vigilance of the concerned actors when they are not prepared for it. The crisis can induce a disruption of balance between the normal course of the radiation therapy and the obligation for the manipulators to reconcile the consequences of the ongoing crisis with the objective of taking charge of all patients scheduled for the program. The crisis and its management will inexorably cause stress, fatigue and, as a consequence, impact patient safety. Management has an essential role to play in maintaining team dynamics when a crisis occurs, the work environment may no longer be the same. The aim of this article is to describe these situations in order to highlight the needs of the teams and more specifically the needs of the radiation therapist. It highlights the organization of patient care in the event of crisis management (Covid-19), during palliative radiotherapy with an opportunity to develop advanced practice. The reflection on the ethical concern of the radiation therapist in the prioritization of patients leads us to analyze the knowledge of medical ethics provided during initial training. When they perform their duties, manipulators seem to be confronted with situations that give rise to ethical dilemmas. It is then a question of understanding how they reflect on their practice in order to make it evolve. Is the radiation therapist confronted with ethical issues in the course of his practice? What solutions can be implemented to deal with these issues?
Assuntos
COVID-19 , Radioterapia (Especialidade) , Pessoal Técnico de Saúde , Humanos , Cuidados Paliativos , PandemiasRESUMO
Toxoplasma gondii proliferates and organizes within a parasitophorous vacuole in rosettes around a residual body and is surrounded by a membranous nanotubular network whose function remains unclear. Here, we characterized structure and function of the residual body in intracellular tachyzoites of the RH strain. Our data showed the residual body as a body limited by a membrane formed during proliferation of tachyzoites probably through the secretion of components and a pinching event of the membrane at the posterior end. It contributes in the intravacuolar parasite organization by the membrane connection between the tachyzoites posterior end and the residual body membrane to give place to the rosette conformation. Radial distribution of parasites in rosettes favors an efficient exteriorization. Absence of the network and presence of atypical residual bodies in a ΔGRA2-HXGPRT knock-out mutant affected the intravacuolar organization of tachyzoites and their exteriorization.
Assuntos
Membrana Celular/ultraestrutura , Proliferação de Células , Estágios do Ciclo de Vida , Toxoplasma/ultraestrutura , Toxoplasmose/patologia , Vacúolos , Animais , Linhagem Celular , Cães , Camundongos , Camundongos Endogâmicos BALB C , Toxoplasma/crescimento & desenvolvimento , Toxoplasmose/metabolismo , Vacúolos/parasitologia , Vacúolos/ultraestruturaRESUMO
BACKGROUND: The association between poverty and intellectual disability (ID) has been well documented. However, little is known about persons with ID who face circumstances of extreme poverty, such as homelessness. This paper describes the situation of persons with ID who were or are homeless in Montreal and are currently receiving services from a team dedicated to homeless persons. AIMS: (1) To describe the characteristics, history and current situation of these persons; and (2) to report within-group differences as a function of gender and current residential status. METHODS: The data were collected from files using an anonymous chart summary. Descriptive statistics on the whole sample (n = 68) and inferential statistics on cross-tabulations by gender and residential status were performed. RESULTS: Persons with ID exhibited several related problems. Some of these persons, primarily women, experienced relatively short periods of homelessness and their situations stabilised once they were identified and followed up. Other persons with ID experienced chronic homelessness that appeared to parallel the number and severity of their other problems. When compared with a previous epidemiological study of the homeless in Montreal, the population of homeless persons with ID differed from the overall homeless population in a number of respects. CONCLUSION: The results suggest prevention and intervention targets. The need for epidemiological research appears particularly clear in light of the fact that below-average intellectual functioning has been identified as a risk factor for homelessness and a predisposing factor for vulnerability among street people.
Assuntos
Pessoas com Deficiência/estatística & dados numéricos , Pessoas Mal Alojadas/estatística & dados numéricos , Deficiência Intelectual/psicologia , Adulto , Idoso , Pessoas com Deficiência/psicologia , Feminino , Pessoas Mal Alojadas/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Apoio Social , Adulto JovemRESUMO
OBJECTIVE: To determine, in serial fixed-flexion (FF) radiographs of subjects with knee osteoarthritis (KOA), the importance of, and basis for, the effect of alignment of the medial tibial plateau (MTP), as determined by the inter-margin distance (IMD), on joint space narrowing (JSN). METHODS: Baseline and 12-month X-rays of 590 knees with Kellgren and Lawrence grade (KLG) 2/3 OA from the public-release dataset of the Osteoarthritis Initiative (OAI) were assigned to subgroups based upon IMD at baseline (IMD(BL)) and the difference between IMD(BL) and IMD(12 mos). Relationships of JSN to IMD(BL) and to the difference between IMD(BL and) IMD(12 mos) were evaluated. RESULTS: In all 590 knees, mean JSN was 0.13 ± 0.51 mm (P<0.0001) and MTP alignment and replication of IMD(BL) in the 12-month film were, in general, poor. JSN was significantly (P=0.012) more rapid in Subgroup A (IMD≤1.70 mm at both time points) than in Subgroup B (both IMDs>1.70 mm): 0.15 ± 0.43; 0.08 ± 0.47. Within Subgroup B we identified a subset, Subgroup B1, in which, although alignment was poor at both time points, the large IMD(BL) was, by chance, highly reproduced by IMD(12 mos) (difference between the two IMDs=0.01 ± 0.27 mm, NS). JSN in Subgroup B1 was 0.06 ± 0.41 mm and did not differ from that in other knees of Subgroup B (P=0.87). The standardized response mean (SRM) in all 590 knees and Subgroups A, B and B1 was 0.25, 0.34, 0.17 and 0.06, respectively. Independent of IMD(BL), JSN correlated significantly with the difference between the IMDs in the two radiographs (r=0.17, P=0.0001). CONCLUSION: Skewed MTP alignment in serial films and poor replication of IMD(BL) in the follow-up exam affect JSN measurement. The magnitude of change in joint space width (JSW) related to the poor quality of alignment that is common with the FF view jeopardizes accurate evaluation of JSN.
Assuntos
Articulação do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/diagnóstico por imagem , Tíbia/diagnóstico por imagem , Idoso , Progressão da Doença , Métodos Epidemiológicos , Feminino , Humanos , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/patologia , RadiografiaRESUMO
AIMS: The CAPTIM (Comparison of primary Angioplasty and Pre-hospital fibrinolysis In acute Myocardial infarction) study found no evidence that a strategy of primary angioplasty was superior in terms of 30-day outcomes to a strategy of pre-hospital fibrinolysis with transfer to an interventional facility in patients managed early at the acute phase of an acute myocardial infarction. The present analysis was designed to compare both strategies at 5 years. METHODS AND RESULTS: The CAPTIM study included 840 patients managed in a pre-hospital setting within 6 h of an acute ST-segment elevation myocardial infarction. Patients were randomized to either a primary angioplasty (n = 421) or a pre-hospital fibrinolysis (rt-PA) with immediate transfer to a centre with interventional facilities (n = 419). Long-term follow-up was obtained in blinded fashion from 795 patients (94.6%). Using an intent-to-treat analysis, all-cause mortality at 5 years was 9.7% in the pre-hospital fibrinolysis group when compared with 12.6% in the primary angioplasty group [HR 0.75 (95% CI, 0.50-1.14); P = 0.18]. For patients included within 2 h, 5 year mortality was 5.8% in the pre-hospital fibrinolysis group when compared with 11.1% in the primary angioplasty group [HR 0.50 (95% CI, 0.25-0.97); P = 0.04], whereas it was, respectively, 14.5 and 14.4% in patients included after 2 h [HR 1.02, (95% CI 0.59-1.75), P = 0.92]. CONCLUSION: The 5-year follow-up is consistent with the 30-day outcomes of the trial, showing similar mortality for primary percutaneous coronary intervention and a policy of pre-hospital lysis followed by transfer to an interventional center. In addition, for patients treated within 2 h of symptom onset, 5-year mortality was lower with pre-hospital lysis.
Assuntos
Angioplastia Coronária com Balão , Infarto do Miocárdio/terapia , Terapia Trombolítica/métodos , Idoso , Angiopatias Diabéticas/tratamento farmacológico , Angiopatias Diabéticas/terapia , Serviços Médicos de Emergência/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Transferência de Pacientes , Análise de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
Diffusion MRI fiber tracking datasets can contain millions of 3D streamlines, and their representation can weight tens of gigabytes of memory. These sets of streamlines are called tractograms and are often used for clinical operations or research. Their size makes them difficult to store, visualize, process or exchange over the network. We propose a new compression algorithm well-suited for tractograms, by taking advantage of the way streamlines are obtained with usual tracking algorithms. Our approach is based on unit vector quantization methods combined with a spatial transformation which results in low compression and decompression times, as well as a high compression ratio. For instance, a 11.5GB tractogram can be compressed to a 1.02GB file and decompressed in 11.3 seconds. Moreover, our method allows for the compression and decompression of individual streamlines, reducing the need for a costly out-of-core algorithm with heavy datasets. Last, we open a way toward on-the-fly compression and decompression for handling larger datasets without needing a load of RAM (i.e. in-core handling), faster network exchanges and faster loading times for visualization or processing.
Assuntos
Algoritmos , Encéfalo , Imagem de Tensor de Difusão/métodos , Processamento de Imagem Assistida por Computador/métodos , HumanosRESUMO
BACKGROUND: We explored the feasibility and the histologic assessment of treatment effect of preoperative chemoradiation in patients presenting with resectable pancreatic adenocarcinoma. PATIENTS AND METHODS: Treatment consisted of concurrent radiotherapy (50 Gy within 5 weeks) and chemotherapy with 5-fluorouracil (300 mg/m(2)/day, 5 days/week, weeks 1-5) and cisplatin (20 mg/m(2)/day, days 1-5 and 29-33), followed by surgical resection of the pancreatic tumor in patients without progression. RESULTS: In all, 41 patients were enrolled; 38 (93%) received >or=47 Gy; 30 patients (73%) received >or=75% of the prescribed doses of chemotherapy. Among 40 assessable patients, 27 (67.5%; 95% confidence interval 50.9% to 81.4%) were successfully treated (entire dose of radiation, >or=75% of the chemotherapy dose, no grade 4 non-hematologic toxicity). In all, 26 patients (63%) underwent surgical resection with curative intent and 21 (80.7%) had R0 resection. A total of 13 of 26 specimens (50%) presented a major pathologic response (>or=80% of severely degenerative cancer cells), with one complete pathologic response. Operative mortality was 2.8%. The local recurrence and 2-year survival rates were 4% and 32%, respectively, for the 26 operated patients. CONCLUSIONS: This proposed preoperative scheme is feasible, does not prevent successful surgery, and provides antitumoral effect associated with major histopathological response in 50% of patients and a high R0 resection rate.
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Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/cirurgia , Taxa de SobrevidaRESUMO
Several studies have shown a cortico-spinal facilitation during motor imagery. This facilitation effect is weaker when the actual hand posture is incompatible with the imagined movement. To determine whether the source of this interference effect arises from online proprioceptive information, we examined transcranial magnetic stimulation (TMS)-induced motor-evoked potentials during motor imagery in the deafferented subject G.L. The patient and 7 control subjects were asked to close their eyes and imagine joining the tips of the thumb and the little finger while maintaining a hand posture compatible or incompatible with the imagined movement. Contrary to control subjects' performance, G.L.'s results show that the facilitation observed during motor imagery was independent of the hand posture. To examine how vision of the hand interacts with the imagery process, G.L. and control subjects performed the same task with the eyes open. Like control subjects, when G.L. looked at her hand, a greater facilitation was observed when her hand posture was compatible with the imagined movement than when it was incompatible. These results suggest that in the absence of proprioception, vision may facilitate or inhibit motor representations and support the idea that limb position in the brain is organized around multisensory representations.
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Córtex Cerebral/fisiologia , Potenciais Evocados/fisiologia , Mãos/fisiologia , Imaginação/fisiologia , Córtex Motor/fisiologia , Movimento/fisiologia , Propriocepção/fisiologia , Medula Espinal/fisiologia , Percepção Visual/fisiologia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Orientação/fisiologia , Análise e Desempenho de TarefasRESUMO
Vagal nerve stimulation (VNS) has shown promising results in various cohorts of non-surgical refractory epilepsy in adults and children. However studies report a significant delay between implantation and clinical response. We describe a cohort of 28 children and adolescents prospectively followed, classified by epileptic syndromes and treated with VNS using a 6-week rapid ramping protocol between January 2000 and March 2005. Our cohort showed favorable outcome within 6 months which was sustained at 24 months: 68% (19/28) showing >or=50% reduction in seizure frequency, including 14% (4/28) who became seizure-free. VNS was particularly efficacious in children with cryptogenic generalized and partial epilepsies. Although adverse events occurred in 68% (19/28) of patients, most were transient. In conclusion, rapid ramping is associated with an early and lasting response in most children but with a slightly higher side-effect rate.
Assuntos
Terapia por Estimulação Elétrica , Epilepsia/terapia , Pediatria , Nervo Vago/fisiologia , Adolescente , Anticonvulsivantes/uso terapêutico , Criança , Comportamento Infantil , Pré-Escolar , Transtornos Cognitivos/etiologia , Estudos de Coortes , Terapia por Estimulação Elétrica/efeitos adversos , Epilepsia/psicologia , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Qualidade de Vida , Estudos Retrospectivos , Fatores de TempoRESUMO
INTRODUCTION: The international consensus conferences concerning schizophrenia and the authorization to market (French AMM) reserve this molecule for the treatment of resistant schizophrenia. Resistant schizophrenia, as defined by the marketing authorisation, corresponds to the absence of improvement in a patient's state despite two successive treatments with antipsychotics, or at least an atypical drug at an adequate dose for a sufficient length of time. OBJECTIVES: Our investigation compares hospital practices to the marketing authorisation and guidelines regarding resistant schizophrenia. METHODS: All clozapine prescriptions delivered by the pharmacists at the Charles Perrens Hospital were recorded during the month of February 2007. General information concerning the patient and his or her treatment were collected, based on different support teams set up in the hospital. First, the hospital administrative program was used to manage the patients. Then, the treatment establishment form, filled out by psychiatrists before the beginning of the treatment, listed all previous treatments given to the patient and indicated any inefficacy or intolerances to prior treatments. Then, a program monitored the delivery of this molecule and finally, prescriptions were recorded to describe present treatment. RESULTS: Our study consisted of 61 patients, mostly male subjects averaging 40 years of age, single, who had been under psychiatric care for about 15 years, and were, for the most part, professionally inactive. Clozapine was prescribed for schizophrenic (90%) and for bipolar patients (10%). Clozapine was also often prescribed for patients whose illness had not improved with prior treatments. The average dose was of 489 mg/day for patients considered stable, i.e., those for whom clozapine was prescribed with efficacy observed for a sufficiently long time. It was associated in 88% of all cases with another psychotropic: anxiolytic (68% of cases), normothymic (26% of cases), antidepressant (16%) and antipsychotic (42%). DISCUSSION: In practice, clozapine seems to be efficient in bipolar disorders, although the marketing authorisation does not envisage this indication. It is never prescribed first, as some recommendations indicate, even though the follow-up of certain treatments does not always seem adequate to appreciate their non-effectiveness. Seldom prescribed alone, clozapine is often associated with another antipsychotic, a practice not favoured by many experts. Our investigation thus confirms the increase in co-prescriptions, particularly in hospital, for patients who have not improved with clozapine alone, a case that is barely taken into consideration in consensus conferences. With the lack of innovative molecules, psychiatrists are prompted to associate several antipsychotics, with the risk of supporting iatrogenic medication, whereas the experts reserve the relevance of such associations because of a lack of randomised studies.
Assuntos
Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adulto , Antipsicóticos/efeitos adversos , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Clozapina/efeitos adversos , Resistência a Medicamentos , Quimioterapia Combinada , França , Humanos , Masculino , Vigilância de Produtos Comercializados , Psicotrópicos/efeitos adversos , Psicotrópicos/uso terapêutico , Esquizofrenia/diagnóstico , Resultado do TratamentoRESUMO
The assessment of fetal well-being at the beginning of labor must lead to an appropriate monitoring, adapted to the present risks. Even if some medical events are unforeseeable, three ways of reflexions get clear: abnormal maternofetal signs at the admission indicate the need for an increased monitoring (NP5); the reading of the medical file could reveal a high-risk pregnancy; at least, the realization of electronic fetal heart rate monitoring for any woman at the beginning of the labor is recommended: in case of normality, it remains a good criterion of a fetal good health. In this context of admission, there is no evidence supporting that other techniques (amnioscopy, acoustic test, echography, Doppler, etc.) could be beneficial in low-risk women and be recommended (NP5). Research is to be continued in this field.
Assuntos
Testes Diagnósticos de Rotina , Monitorização Fetal/métodos , Trabalho de Parto , Feminino , Fetoscopia , Frequência Cardíaca Fetal , Humanos , Gravidez , Fatores de Risco , Ultrassonografia Pré-NatalRESUMO
The aim of this work is to answer constructively to C. Le Ray and F. Audibert who were surprised that the French guidelines recommended an assisted delivery after 30 min pushing, even if the fetal heart rate is reassuring. We first resumed the definition of "second stage of labor", this word including the first phase with no pushing efforts and the second phase with active pushing of the mother. With that definition, the length of the second stage is around 60 min for the primipara and 20 min for the multipara, this length being modified by the use of peridural. We then specified the physiological mechanisms influencing the acidobasic equilibrium during the pushing time. Those mechanisms are difficult to consider because foetal heart rate monitoring is often "lost" during that phase. Altogether, these factors bring incertitude about progressive foetal acidosis and incapacity to diagnose it. Finally, the literature analysis teaches us that increasing the second stage of labor (inactive plus active phases) during the normal pregnancy seems to be at low risk for the foetus within the primiparas, but display a risk for the mother and so might be limited. Comparing the delayed pushing with the immediate pushing only lead us to conclude that delayed pushing is dangerous, as is prolonged second stage. In conclusion, we think that prolonging the second stage of labor is possible but must be by increasing the inactive first phase of the second stage, especially as long as we will not get a noninvasive and reliable method allowing assessing the well-being of the foetus.