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1.
Ann Surg ; 275(4): 735-742, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32740249

RESUMO

OBJECTIVE: The aim of this study was to assess the effectiveness of sacral nerve modulation (SNM) in a large cohort of patients implanted for at least 10 years, quantify adverse event rates, and identify predictive factors of long-term success. SUMMARY BACKGROUND DATA: Few studies have evaluated the long-term success of SNM. METHODS: Data collected prospectively from patients implanted for fecal incontinence (FI) in 7 French centers between January 1998 and December 2008 were retrospectively analyzed. Patient FI severity scores were assessed before and 10 years after implantation. The main evaluation criterion was the success of SNM defined by the continuation of the treatment without additional therapies. The secondary evaluation criteria were the rate of device revisions and explantations. Preoperative predictors of success at 10 years were sought. RESULTS: Of the 360 patients (27 males, mean age: 59 ± 12 years) implanted for FI, 162 (45%) had a favorable outcome 10 years post-implantation, 115 (31.9%) failed, and 83 (23.1%) were lost to follow-up. The favorable outcome derived from the time-to-event Kaplan-Meier curve at 10 years was 0.64 (95% CI 0.58-0.69). FI severity scores were significantly better 10 years post-implantation compared to preimplantation (7.4 ± 4.3 vs 14.0 ± 3.2; P < 0.0001). During the 10-year follow-up, 233 patients (64.7%) had a surgical revision and 94 (26.1%) were explanted. A history of surgery for FI and sex (male) were associated with an increased risk of an unfavorable outcome. CONCLUSIONS: Long-term efficacy was maintained in approximately half of the FI patients treated by SNM at least 10 years post-implantation.


Assuntos
Terapia por Estimulação Elétrica , Incontinência Fecal , Idoso , Terapia por Estimulação Elétrica/efeitos adversos , Terapia por Estimulação Elétrica/métodos , Incontinência Fecal/cirurgia , Feminino , França , Humanos , Plexo Lombossacral , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
2.
Colorectal Dis ; 23(9): 2228-2285, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34060715

RESUMO

This is a comprehensive and rigorous review of currently available data on the use of mesh in the pelvis in colorectal surgery. This guideline outlines the limitations of available data and the challenges of interpretation, followed by best possible recommendations.


Assuntos
Cirurgia Colorretal , Procedimentos Cirúrgicos do Sistema Digestório , Humanos , Pelve/cirurgia , Próteses e Implantes , Telas Cirúrgicas
3.
Int J Pediatr Otorhinolaryngol ; 146: 110764, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33992972

RESUMO

OBJECTIVE: Microtia is a congenital auricular malformation, often part of a syndromic form (35%-55% of cases). The accurate prevalence of associated malformations remains to be determined with regard to the heterogeneous results of the previous studies. This study aims to describe in a large population cohort the abnormalities associated with microtia and to determine the most suitable assessment for these children. METHODS: This is a retrospective and observational cohort study collecting data from the medical records of children affected by microtia, diagnosed or followed-up between 2007 and 2017. Data were collected via a computer database. Clinical data, as well as imaging or genetic results, were noted. RESULTS: Six hundred ninety four children were included, 587 (84.6%) with unilateral and 107 (15.4%) with bilateral microtia. Inner ear malformations were observed in 14.1% of the ears. The main associated anomalies were hemifacial microsomia (29%), velopharyngeal insufficiency (9%), ophthalmologic (6.2%), vertebral (5.9%), cardiac (5.5%) and kidney (3%) abnormalities. Main identified entities were Goldenhar, Treacher-Collins and Guion-Almeida syndromes. CONCLUSION: A comprehensive clinical assessment must be completed when microtia is diagnosed. Besides screening well-known oculo-auriculo-vertebral spectrum malformations, velopharyngeal insufficiency should be systematically sought. Specialized care must be provided to the very frequently associated hemifacial macrosomia. Mild forms of this last malformation may correspond to Guion-Almeida syndrome, especially in cases of learning disability.


Assuntos
Anormalidades Congênitas , Microtia Congênita , Síndrome de Goldenhar , Criança , Anormalidades Congênitas/diagnóstico , Anormalidades Congênitas/epidemiologia , Microtia Congênita/epidemiologia , Orelha , Síndrome de Goldenhar/diagnóstico , Síndrome de Goldenhar/epidemiologia , Humanos , Estudos Retrospectivos , Coluna Vertebral
4.
Cell Rep ; 35(6): 109121, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33979625

RESUMO

The vascular endothelial growth factor (VEGF) pathway regulates key processes in synapse function, which are disrupted in early stages of Alzheimer's disease (AD) by toxic-soluble amyloid-beta oligomers (Aßo). Here, we show that VEGF accumulates in and around Aß plaques in postmortem brains of patients with AD and in APP/PS1 mice, an AD mouse model. We uncover specific binding domains involved in direct interaction between Aßo and VEGF and reveal that this interaction jeopardizes VEGFR2 activation in neurons. Notably, we demonstrate that VEGF gain of function rescues basal synaptic transmission, long-term potentiation (LTP), and dendritic spine alterations, and blocks long-term depression (LTD) facilitation triggered by Aßo. We further decipher underlying mechanisms and find that VEGF inhibits the caspase-3-calcineurin pathway responsible for postsynaptic glutamate receptor loss due to Aßo. These findings provide evidence for alterations of the VEGF pathway in AD models and suggest that restoring VEGF action on neurons may rescue synaptic dysfunction in AD.


Assuntos
Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Sinapses/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Humanos , Camundongos
5.
Viruses ; 12(9)2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32839386

RESUMO

Group-B enteroviruses (EV-B) are ubiquitous naked single-stranded positive RNA viral pathogens that are responsible for common acute or persistent human infections. Their genome is composed in the 5' end by a non-coding region, which is crucial for the initiation of the viral replication and translation processes. RNA domain-I secondary structures can interact with viral or cellular proteins to form viral ribonucleoprotein (RNP) complexes regulating viral genomic replication, whereas RNA domains-II to -VII (internal ribosome entry site, IRES) are known to interact with cellular ribosomal subunits to initiate the viral translation process. Natural 5' terminally deleted viral forms lacking some genomic RNA domain-I secondary structures have been described in EV-B induced murine or human infections. Recent in vitro studies have evidenced that the loss of some viral RNP complexes in the RNA domain-I can modulate the viral replication and infectivity levels in EV-B infections. Moreover, the disruption of secondary structures of RNA domain-I could impair viral RNA sensing by RIG-I (Retinoic acid inducible gene I) or MDA5 (melanoma differentiation-associated protein 5) receptors, a way to overcome antiviral innate immune response. Overall, natural 5' terminally deleted viral genomes resulting in the loss of various structures in the RNA domain-I could be major key players of host-cell interactions driving the development of acute or persistent EV-B infections.


Assuntos
Enterovirus Humano B/genética , Infecções por Enterovirus/virologia , RNA não Traduzido/genética , RNA Viral/química , RNA Viral/genética , Animais , Enterovirus Humano B/fisiologia , Genoma Viral , Interações Hospedeiro-Patógeno , Humanos , Interferons/metabolismo , Conformação de Ácido Nucleico , Biossíntese de Proteínas , RNA não Traduzido/química , RNA não Traduzido/metabolismo , RNA Viral/metabolismo , Transdução de Sinais , Proteínas Virais/química , Proteínas Virais/genética , Proteínas Virais/metabolismo , Replicação Viral
6.
Radiother Oncol ; 146: 167-171, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32171944

RESUMO

OBJECTIVE: To assess the efficacy and safety of sacral nerve modulation (SNM) in patients with faecal incontinence (FI) after pelvic radiotherapy in comparison with results of SNM for FI related to other conditions. METHODS: Prospectively collected data from patients who underwent SNM therapy between January 2010 and December 2015 at 7 tertiary colorectal units were reviewed retrospectively. Patients with FI following pelvic radiotherapy were identified and matched (1:2) for age and sex with 38 patients implanted over the same period for FI without previous radiotherapy. The treatment was considered favourable if the patient reported any therapeutic benefit from SNM, had no further complaints or interventions and did not consider stopping the treatment. Long-term results, surgical revision and definitive explantation rates were compared. RESULTS: Among 352 patients who received a permanent SNM implant, 19 (5.4%) had FI following pelvic radiotherapy. After a mean follow-up of 3.5 ± 1.9 years, the cumulative successful treatment rates were similar between the groups (p = 0.60). For patients with FI following pelvic radiotherapy, the cumulative success rates were 99.4% [85.4-99.8], 96.7% [78.1-99.6], 91.7% [70.4-98.1] and 74.6% [48.4-94.8] at 1, 2, 3 and 5 years respectively. The revision and definitive explantation rates for infection did not differ significantly. CONCLUSION: The long-term success rate of SNM for FI after pelvic radiotherapy is similar to that of SNM for FI related to other more frequent conditions. Our study suggests that FI after pelvic radiotherapy could be improved with SNM without an increased risk of complication.


Assuntos
Terapia por Estimulação Elétrica , Incontinência Fecal , Eletrodos Implantados , Incontinência Fecal/etiologia , Humanos , Estudos Retrospectivos , Resultado do Tratamento
7.
Int J Pediatr Otorhinolaryngol ; 123: 33-37, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31059930

RESUMO

INTRODUCTION: Desmoid-type fibromatosis (DF) is a rare benign lesion known for its local aggressiveness. The tumor management still remains under debate. Primary head and neck (HN), represents the second most prevalently affected sitein children with DF. This study aims to analyze the specificity of HN-DF in children, focusing on long-term effects of the tumor and therapies. METHODS: This retrospective multicenter study analyzed children treated for a HN-DF between 1993 and 2013. All medical files were reviewed and their outcomes analyzed according to the initial therapies provided. RESULTS: Sixteen children were selected. Mandibular and submandibular areas were the main locations (11 cases). Eight children underwent chemotherapy as first-line therapy with tumor control in 3 cases and 5 cases needing additional treatment. Six children underwent primary surgery: isolated in 3 cases and with additional treatment after tumor progression in 3 cases. A wait-and-see attitude was adopted for 2 children without any additional treatment in 1 case, and followed by additional chemotherapy in the other case. Total burden of treatment to control the disease was a biopsy (1 case), surgery (3 unique cases, 1 multiple case), surgery with chemotherapy (6 cases), and exclusive medical therapies (5 cases). Surgical postoperative sequelae were facial palsy (cases of parotid gland affection), XIth cranial nerve sacrifice or sensory impairment. CONCLUSION: HN-DF is a local and extensive disease that is difficult to control with surgery alone. Sequelae are frequent due to the initial tumor location or therapies. Initial conservative strategies need to be discussed in a multidisciplinary way in order to try to control the disease with the minimal morbidity.


Assuntos
Fibromatose Agressiva/tratamento farmacológico , Fibromatose Agressiva/cirurgia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias Mandibulares/tratamento farmacológico , Neoplasias Mandibulares/cirurgia , Adolescente , Antineoplásicos/uso terapêutico , Paralisia de Bell/etiologia , Criança , Pré-Escolar , Terapia Combinada , Progressão da Doença , Feminino , Fibromatose Agressiva/terapia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Lactente , Masculino , Neoplasias Mandibulares/terapia , Glândula Parótida/patologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Conduta Expectante
8.
Circulation ; 139(20): 2326-2338, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-30755025

RESUMO

BACKGROUND: Group B enteroviruses are common causes of acute myocarditis, which can be a precursor of chronic myocarditis and dilated cardiomyopathy, leading causes of heart transplantation. To date, the specific viral functions involved in the development of dilated cardiomyopathy remain unclear. METHODS: Total RNA from cardiac tissue of patients with dilated cardiomyopathy was extracted, and sequences corresponding to the 5' termini of enterovirus RNAs were identified. After next-generation RNA sequencing, viral cDNA clones mimicking the enterovirus RNA sequences found in patient tissues were generated in vitro, and their replication and impact on host cell functions were assessed on primary human cardiac cells in culture. RESULTS: Major enterovirus B populations characterized by 5' terminal genomic RNA deletions ranging from 17 to 50 nucleotides were identified either alone or associated with low proportions of intact 5' genomic termini. In situ hybridization and immunohistological assays detected these persistent genomes in clusters of cardiomyocytes. Transfection of viral RNA into primary human cardiomyocytes demonstrated that deleted forms of genomic RNAs displayed early replication activities in the absence of detectable viral plaque formation, whereas mixed deleted and complete forms generated particles capable of inducing cytopathic effects at levels distinct from those observed with full-length forms alone. Moreover, deleted or full-length and mixed forms of viral RNA were capable of directing translation and production of proteolytically active viral proteinase 2A in human cardiomyocytes. CONCLUSIONS: We demonstrate that persistent viral forms are composed of B-type enteroviruses harboring a 5' terminal deletion in their genomic RNAs and that these viruses alone or associated with full-length populations of helper RNAs could impair cardiomyocyte functions by the proteolytic activity of viral proteinase 2A in cases of unexplained dilated cardiomyopathy. These results provide a better understanding of the molecular mechanisms that underlie the persistence of EV forms in human cardiac tissues and should stimulate the development of new therapeutic strategies based on specific inhibitors of the coxsackievirus B proteinase 2A activity for acute and chronic cardiac infections.


Assuntos
Regiões 5' não Traduzidas/genética , Cardiomiopatia Dilatada/virologia , Cisteína Endopeptidases/genética , Enterovirus Humano B/isolamento & purificação , Miócitos Cardíacos/virologia , RNA Viral/genética , Proteínas Virais/genética , Cardiomiopatia Dilatada/etiologia , Cardiomiopatia Dilatada/patologia , Células Cultivadas , Cisteína Endopeptidases/biossíntese , Efeito Citopatogênico Viral , DNA Complementar/genética , Enterovirus Humano B/genética , Enterovirus Humano B/fisiologia , Infecções por Enterovirus/complicações , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Miocardite/complicações , Miocardite/virologia , Deleção de Sequência , Transfecção , Proteínas Virais/biossíntese , Latência Viral , Replicação Viral
9.
Ann Surg ; 269(2): 310-314, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-28902668

RESUMO

OBJECTIVE: Magnetic anal sphincter augmentation is a novel surgical option in the treatment of severe fecal incontinence. This study aimed to analyze functional results, quality of life, and satisfaction after implantation in the mid-term, and to identify factors associated with success of this new treatment. METHODS: All patients, who underwent magnetic anal sphincter augmentation procedure at a single center between December 2008 and January 2016, were consecutively included. Symptom severity [Cleveland Clinic Incontinence Score (CCIS)], quality of life [Fecal-Incontinence Quality of Life Questionnaire (FIQL)], bowel diary data, and patients' satisfaction were assessed before and after implantation. RESULTS: Forty-five patients (43 female), mean (s.d.) age 66.82 (±10.07), were followed for a median of 36 months (range 6-84). Two patients were explanted and 1 lost to follow-up. On a 3-week diary, major leakage rate significantly improved as did CCIS and FIQL. No significant difference was seen for flatus and minor leaks. Postoperative decrease of CCIS by ≥5.5 points correlated best with satisfaction, expressed by 22 patients (48% in intention-to-treat analysis). An independent predictive factor for success after implantation was no previous fecal incontinence surgical treatment. CONCLUSIONS: Satisfaction, functional, and quality of life outcomes improve significantly following magnetic anal sphincter augmentation.


Assuntos
Canal Anal/cirurgia , Incontinência Fecal/cirurgia , Qualidade de Vida , Idoso , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Feminino , Humanos , Masculino , Satisfação do Paciente , Recuperação de Função Fisiológica , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
10.
Obes Surg ; 29(2): 609-616, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30448982

RESUMO

BACKGROUND: Obesity is a well-known risk factor for female pelvic floor disorders (PFD). This study assessed the effects of bariatric surgery (BS) on pelvic organ prolapse symptoms (POPs) and urinary (UI) and anal incontinence (AI) in morbidly obese women undergoing either sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). METHODS: Morbidly obese women undergoing BS from June 2016 to May 2017 were prospectively included. POPs, UI, and AI were compared at baseline and at 1 year after surgery using validated questionnaires. RESULTS: Seventy-two consecutive women were enrolled, 54 (75%) (30 (56%) RYBP and 24 (44%) SG) completed the study at 1 year and were considered for the final analysis. The mean age and mean preoperative BMI were 43 ± 11.8 years (range, 20-65) and 41 ± 5.4 kg/m2 (range, 35-56), respectively. At baseline, 30 (56%), 32 (59%), and 27 (50%) patients, respectively, had AI (flatus only 72%), UI, and POPs. The mean TBWL% at 1 year was 33%. In the whole study population, weight loss was associated with a significant improvement in UI (p < 0.001) but there was no significant difference in terms of AI and POPs. In the subgroups analysis, AI increased significantly 1 year after the RYGB (p = 0.02) due to an increase in flatus incontinence (p = 0.04). No significant difference in AI was found 1 year after the SG. CONCLUSION: BS is associated with a significant improvement in UI but not in POPs. RYBP seems to increase AI, mainly flatus incontinence, compared to SG.


Assuntos
Incontinência Fecal/cirurgia , Gastrectomia , Derivação Gástrica , Prolapso de Órgão Pélvico/cirurgia , Incontinência Urinária/cirurgia , Adulto , Idoso , Incontinência Fecal/etiologia , Feminino , Flatulência , Humanos , Laparoscopia , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Prolapso de Órgão Pélvico/etiologia , Projetos Piloto , Estudos Prospectivos , Incontinência Urinária/etiologia , Adulto Jovem
11.
Int J Pediatr Otorhinolaryngol ; 110: 61-66, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29859590

RESUMO

OBJECTIVES: To investigate the outcomes of rigid endoscope-assisted orotracheal intubation (REI) in neonates and young infants with difficult airway conditions as an alternative intubation technique when more specific airway instruments are not available in most developing countries, and to evaluate the safety and advantages of this method. METHODS: Neonatal and young infantile patients undergoing vallecular cyst surgery with a Cormack-Lehane Grade 3 or 4 glottic view between June 2013 and June 2015 were studied. Fifteen patients were intubated using rigid endoscopic assistance. Fifteen other patients who were intubated using the conventional technique were selected from the previous consecutive cases and used as a matched control group. RESULTS: REI was successfully performed in all 15 patients in one intubation attempt. The anesthetic preparation duration for the REI group was 6 min (interquartile range 5-7 min), which was shorter than the anesthetic preparation duration for patients intubated using the conventional technique (15 min [interquartile range 10-20 min], p < 0.001). The time required for intubation with a rigid endoscope was 66.5 s (interquartile range 58-74 s). No volume reduction of cysts or tracheotomies was needed in the REI group, and no cysts were ruptured nor did laryngeal mucosa damage occur with this technique. Among patients of conventional group, one required a tracheotomy, and four required cyst volume reduction by needle aspiration. No residual lesions or recurrence were observed during one year of postoperative follow-up in the REI group, and two recurrences were observed in the conventional group. CONCLUSION: REI, which used common pieces of equipment in an otolaryngology operating room, may be a safe and feasible alternative for intubation in neonatal and young infantile patients with vallecular cysts or other difficult airway conditions.


Assuntos
Cistos/cirurgia , Endoscópios , Intubação Intratraqueal/instrumentação , Doenças da Laringe/cirurgia , Feminino , Gastroenteropatias/cirurgia , Humanos , Lactente , Recém-Nascido , Intubação Intratraqueal/efeitos adversos , Intubação Intratraqueal/métodos , Masculino , Recidiva , Fatores de Tempo , Traqueotomia
12.
J Zoo Wildl Med ; 49(2): 291-296, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29900770

RESUMO

To define a protocol of anesthesia for long-duration invasive surgery in a lizard, eight young adult Argentine tegus ( Salvator merianae) of mean body weight 3.0 kg (interquartile range [IQR] 3.40-2.65) were anesthetized with a mixture of ketamine (K) and medetomidine (M) at 19°C, injected intramuscularly and equally distributed in the four limbs. As the experimental surgery procedure required a prolonged deep anesthesia with a good myorelaxation (between 16 and 21 hr), reinjections were required and reflexes were checked during surgery. Times for anesthetic induction, anesthetic reinjection, and recovery periods were recorded for five different combinations of ketamine-medetomidine: 1) 66 mg/kg K + 100 µg/kg M; 2) 80 mg/kg K + 100 µg/kg M; 3) 100 mg/kg K + 130 µg/kg M; 4) 125 mg/kg K + 200 µg/kg M; and 5) 150 mg/kg K + 200 µg/kg M. The effect on the recovery speed of the postoperative atipamezole injection was also evaluated. The median induction time was 30 (IQR 35-27.5) min with no statistical difference between all the concentrations tested. The first reinjection of half a dose was administered after a mean of 5 hr (5.64 hr, IQR 5.95-4.84) as were the subsequent reinjections of a quarter dose (3.99 hr, IQR 5.98-3.23). Intramuscular administration of the ketamine-medetomidine combination is a simple, rapid, and efficient anesthesia for long-term surgery (>12 hr). A mix of 100 mg/kg ketamine and 200 µg/kg medetomidine, with reinjections every 4 hr of half a dose of the previous injection can maintain a good quality of anesthesia for at least 16 hr. The injection of atipamezole after the surgery reverses the effects of medetomidine and permits a reduction of the recovery period.


Assuntos
Anestesia/veterinária , Anestésicos Dissociativos/farmacologia , Hipnóticos e Sedativos/farmacologia , Ketamina/farmacologia , Lagartos/fisiologia , Medetomidina/farmacologia , Anestésicos Dissociativos/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Feminino , Hipnóticos e Sedativos/administração & dosagem , Injeções Intramusculares/veterinária , Ketamina/administração & dosagem , Masculino , Medetomidina/administração & dosagem
13.
Nat Commun ; 9(1): 504, 2018 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-29402935

RESUMO

Despite decades of research, there is a persistent debate regarding the localization of GABA/glycine neurons responsible for hyperpolarizing somatic motoneurons during paradoxical (or REM) sleep (PS), resulting in the loss of muscle tone during this sleep state. Combining complementary neuroanatomical approaches in rats, we first show that these inhibitory neurons are localized within the ventromedial medulla (vmM) rather than within the spinal cord. We then demonstrate their functional role in PS expression through local injections of adeno-associated virus carrying specific short-hairpin RNA in order to chronically impair inhibitory neurotransmission from vmM. After such selective genetic inactivation, rats display PS without atonia associated with abnormal and violent motor activity, concomitant with a small reduction of daily PS quantity. These symptoms closely mimic human REM sleep behavior disorder (RBD), a prodromal parasomnia of synucleinopathies. Our findings demonstrate the crucial role of GABA/glycine inhibitory vmM neurons in muscle atonia during PS and highlight a candidate brain region that can be susceptible to α-synuclein-dependent degeneration in RBD patients.


Assuntos
Bulbo/fisiologia , Neurônios/fisiologia , Sono REM/fisiologia , Animais , Técnicas de Silenciamento de Genes , Glicina/metabolismo , Masculino , Bulbo/citologia , Hipotonia Muscular/fisiopatologia , Polissonografia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Transtorno do Comportamento do Sono REM/fisiopatologia , Ratos Sprague-Dawley , Transmissão Sináptica/genética , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/genética , Ácido gama-Aminobutírico/metabolismo
14.
Am J Hum Genet ; 101(6): 1006-1012, 2017 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-29198720

RESUMO

Leber congenital amaurosis (LCA) is a neurodegenerative disease of photoreceptor cells that causes blindness within the first year of life. It occasionally occurs in syndromic metabolic diseases and plurisystemic ciliopathies. Using exome sequencing in a multiplex family and three simplex case subjects with an atypical association of LCA with early-onset hearing loss, we identified two heterozygous mutations affecting Arg391 in ß-tubulin 4B isotype-encoding (TUBB4B). Inspection of the atomic structure of the microtubule (MT) protofilament reveals that the ß-tubulin Arg391 residue contributes to a binding pocket that interacts with α-tubulin contained in the longitudinally adjacent αß-heterodimer, consistent with a role in maintaining MT stability. Functional analysis in cultured cells overexpressing FLAG-tagged wild-type or mutant TUBB4B as well as in primary skin-derived fibroblasts showed that the mutant TUBB4B is able to fold, form αß-heterodimers, and co-assemble into the endogenous MT lattice. However, the dynamics of growing MTs were consistently altered, showing that the mutations have a significant dampening impact on normal MT growth. Our findings provide a link between sensorineural disease and anomalies in MT behavior and describe a syndromic LCA unrelated to ciliary dysfunction.


Assuntos
Amaurose Congênita de Leber/genética , Microtúbulos/genética , Tubulina (Proteína)/genética , Adulto , Sítios de Ligação/genética , Células Cultivadas , Criança , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Microtúbulos/metabolismo , Pessoa de Meia-Idade , Mutação de Sentido Incorreto/genética , Células Fotorreceptoras/metabolismo , Tubulina (Proteína)/metabolismo , Sequenciamento do Exoma
15.
Dis Colon Rectum ; 60(9): 965-970, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28796735

RESUMO

BACKGROUND: Laparoscopic peritoneal lavage is an alternative to sigmoid resection in Hinchey III diverticulitis (generalized purulent peritonitis). The main limitation of laparoscopic peritoneal lavage is the higher rate of reoperation for persistent sepsis in comparison with sigmoid resection. OBJECTIVE: The purpose of the current study was to identify risk factors for laparoscopic peritoneal lavage failure in patients who have Hinchey III diverticulitis. DESIGN: This was a retrospective multicenter study. SETTINGS: The study was conducted in 3 clinical sites in France. PATIENTS: From 2006 to 2015, all consecutive patients undergoing emergent surgery for diverticulitis were reviewed. All patients operated on with laparoscopic peritoneal lavage for laparoscopically confirmed Hinchey III diverticulitis were included. MAIN OUTCOME MEASURES: The main outcome was laparoscopic peritoneal lavage failure, defined as reoperation or death at 30 postoperative days. RESULTS: A series of 71 patients (43 men, mean age 58 ± 15 years) were operated on with laparoscopic peritoneal lavage for Hinchey III diverticulitis. Laparoscopic peritoneal lavage failed in 14 (20%) of them: 1 died and 13 underwent reoperations. No major complication (Dindo-Clavien score ≥3) occurred after reoperation. Immunosuppressive drugs (p = 0.01) and ASA grade ≥3 (p = 0.02) were associated with laparoscopic peritoneal lavage failure after univariate analysis. Multivariate analysis identified only immunosuppressive drug intake (steroids or chemotherapy for cancer) as an independent predictive factor. Mean length of stay was 14.9 days (5-67). At the end of the 30 first postoperative days, 12 (17%) patients had a stoma. LIMITATIONS: The study was limited by its retrospective nature and the small size of the cohort. CONCLUSION: Our results highlight immunosuppressive drug intake as a major risk factor for laparoscopic peritoneal lavage failure in patients who have Hinchey III diverticulitis. Immunosuppression and severe comorbidities (ASA ≥3) should be considered when selecting a surgical option in patients with Hinchey III diverticulitis. See Video Abstract at http://links.lww.com/DCR/A423.


Assuntos
Doença Diverticular do Colo , Laparoscopia , Lavagem Peritoneal , Peritonite , Complicações Pós-Operatórias , Adulto , Idoso , Colo Sigmoide/patologia , Colo Sigmoide/cirurgia , Comorbidade , Doença Diverticular do Colo/complicações , Doença Diverticular do Colo/diagnóstico , Doença Diverticular do Colo/epidemiologia , Doença Diverticular do Colo/cirurgia , Tratamento de Emergência/métodos , Feminino , França/epidemiologia , Humanos , Imunossupressores/uso terapêutico , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Lavagem Peritoneal/efeitos adversos , Lavagem Peritoneal/métodos , Peritonite/diagnóstico , Peritonite/etiologia , Peritonite/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Reoperação/efeitos adversos , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Falha de Tratamento
16.
Brain ; 140(2): 414-428, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28007991

RESUMO

SEE SCHENCK AND MAHOWALD DOI101093/AWW329 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Idiopathic REM sleep behaviour disorder is characterized by the enactment of violent dreams during paradoxical (REM) sleep in the absence of normal muscle atonia. Accumulating clinical and experimental data suggest that REM sleep behaviour disorder might be due to the neurodegeneration of glutamate neurons involved in paradoxical sleep and located within the pontine sublaterodorsal tegmental nucleus. The purpose of the present work was thus to functionally determine first, the role of glutamate sublaterodorsal tegmental nucleus neurons in paradoxical sleep and second, whether their genetic inactivation is sufficient for recapitulating REM sleep behaviour disorder in rats. For this goal, we first injected two retrograde tracers in the intralaminar thalamus and ventral medulla to disentangle neuronal circuits in which sublaterodorsal tegmental nucleus is involved; second we infused bilaterally in sublaterodorsal tegmental nucleus adeno-associated viruses carrying short hairpin RNAs targeting Slc17a6 mRNA [which encodes vesicular glutamate transporter 2 (vGluT2)] to chronically impair glutamate synaptic transmission in sublaterodorsal tegmental nucleus neurons. At the neuroanatomical level, sublaterodorsal tegmental nucleus neurons specifically activated during paradoxical sleep hypersomnia send descending efferents to glycine/GABA neurons within the ventral medulla, but not ascending projections to the intralaminar thalamus. These data suggest a crucial role of sublaterodorsal tegmental nucleus neurons rather in muscle atonia than in paradoxical sleep generation. In line with this hypothesis, 30 days after adeno-associated virus injections into sublaterodorsal tegmental nucleus rats display a decrease of 30% of paradoxical sleep daily quantities, and a significant increase of muscle tone during paradoxical sleep concomitant to a tremendous increase of abnormal motor dream-enacting behaviours. These animals display symptoms and behaviours during paradoxical sleep that closely mimic human REM sleep behaviour disorder. Altogether, our data demonstrate that glutamate sublaterodorsal tegmental nucleus neurons generate muscle atonia during paradoxical sleep likely through descending projections to glycine/GABA premotor neurons in the ventral medulla. Although playing a role in paradoxical sleep regulation, they are, however, not necessary for inducing the state itself. The present work further validates a potent new preclinical REM sleep behaviour disorder model that opens avenues for studying and treating this disabling sleep disorder, and advances potential regions implicated in prodromal stages of synucleinopathies such as Parkinson's disease.


Assuntos
Ácido Glutâmico/metabolismo , Neurônios/fisiologia , Área Pré-Tectal/patologia , Transtorno do Comportamento do Sono REM/patologia , Animais , Contagem de Células , Toxina da Cólera/farmacocinética , Dependovirus/genética , Modelos Animais de Doenças , Transportador 5 de Aminoácido Excitatório/genética , Transportador 5 de Aminoácido Excitatório/metabolismo , Regulação da Expressão Gênica/genética , Proteínas da Membrana Plasmática de Transporte de Glicina/genética , Proteínas da Membrana Plasmática de Transporte de Glicina/metabolismo , Masculino , Área Pré-Tectal/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Transtorno do Comportamento do Sono REM/etiologia , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Privação do Sono/complicações , Análise Espectral , Estilbamidinas/farmacocinética
18.
PLoS One ; 10(11): e0142065, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26528714

RESUMO

How does the brain discriminate essential information aimed to be stored permanently from information required only temporarily, and that needs to be cleared away for not saturating our precious memory space? Reference Memory (RM) refers to the long-term storage of invariable information whereas Working Memory (WM) depends on the short-term storage of trial-unique information. Previous work has revealed that WM tasks are very sensitive to proactive interference. In order to prevent such interference, irrelevant old memories must be forgotten to give new ones the opportunity to be stabilized. However, unlike memory, physiological processes underlying this adaptive form of forgetting are still poorly understood. Here, we precisely ask what specific brain structure(s) could be responsible for such process to occur. To answer this question, we trained rats in a radial maze using three paradigms, a RM task and two WM tasks involving or not the processing of interference but strictly identical in terms of locomotion or motivation. We showed that an inhibition of the expression of Zif268 and c-Fos, two indirect markers of neuronal activity and synaptic plasticity, was observed in the dentate gyrus of the dorsal hippocampus when processing such interfering previously stored information. Conversely, we showed that inactivating the dentate gyrus impairs both RM and WM, but improves the processing of interference. Altogether, these results strongly suggest for the first time that the dentate gyrus could be a key structure involved in adaptive forgetting.


Assuntos
Adaptação Psicológica/fisiologia , Giro Denteado/fisiologia , Memória de Curto Prazo/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/metabolismo , Animais , Proteína 1 de Resposta de Crescimento Precoce/biossíntese , Regulação da Expressão Gênica/fisiologia , Proteínas Proto-Oncogênicas c-fos/biossíntese , Ratos
19.
Surg Endosc ; 29(3): 620-6, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25030476

RESUMO

BACKGROUND: The percutaneous endoscopic ceacostomy (PEC) for antegrade colonic enemas (ACE) has recently been proposed as a less invasive alternative to the Malone procedure in chronic constipated patients. Although the feasibility and safety of this innovative approach has been demonstrated, its functional results remain unknown. The aim of this study was to evaluate constipation symptoms and quality of life 1 year after the PEC placement. METHOD: From Oct 2007 to Apr 2011, 21 severely constipated patients who required ACE were prospectively included. They underwent endoscopic placement of Chait caecostomy catheter (Cook Medical). Patients completed standardized questionnaires to assess constipation (KESS) and quality of life (GIQLI) scores pre PEC placement and at 1 year. Adverse events and caecostomy use data were also documented. RESULTS: The caecostomy catheter was successfully placed in 19 patients. Complications were all minor, including chronic wound pain (n = 9), serous leakage (n = 7), superficial wound infection (n = 2) and accidental catheter removal (n = 2). Chronic wound pain led to definitive catheter removal in 5 (26 %) patients. One patient died from unrelated cause before the end of the follow-up. At 1 year, 11 (61 %) of the alive patients still performed ACE. During the period of ACE administration, 14 (74 %) patients suspended use of laxatives and retrograde irrigations. Constipation and quality of life scores were available in 15 patients. Median KESS score improved from 25 (12-39) before PEC to 17 (6-34) 1 year after PEC (p < 0.05). Median GIQLI score increased from 69 (25-108) to 95 (48-119) (p < 0.05). CONCLUSION: PEC placement achieves satisfying functional and quality of life results, and allows approximately 3/4 of patients to suspend laxatives and retrograde enemas. Nevertheless, 1/4 of the patients ask for the PEC removal because of chronic wound pain. In order to improve long-term durability of the device, a better prevention of pain is required.


Assuntos
Cecostomia/métodos , Ceco/cirurgia , Constipação Intestinal/cirurgia , Defecação/fisiologia , Endoscopia do Sistema Digestório/métodos , Qualidade de Vida , Adulto , Idoso , Ceco/fisiopatologia , Constipação Intestinal/fisiopatologia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
Artigo em Inglês | MEDLINE | ID: mdl-25122397

RESUMO

We develop a semirelativistic quantum fluid theory based on the expansion of the Dirac Hamiltonian to second order in 1/c. By making use of the Madelung representation of the wave function, we derive a set of hydrodynamic equations that comprises a continuity equation, an Euler equation for the mean velocity, and an evolution equation for the electron spin density. This hydrodynamic model is then applied to study the dynamics of a dense and weakly relativistic electron plasma. In particular, we investigate the impact of the quantum-relativistic spin effects on the Faraday rotation in a one-dimensional plasma slab irradiated by an x-ray laser source.


Assuntos
Elétrons , Gases , Hidrodinâmica , Luz , Modelos Teóricos , Teoria Quântica , Lasers , Temperatura
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