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1.
BMC Oral Health ; 24(1): 142, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287339

RESUMO

PURPOSE: The purpose of this study was to evaluate the suitability, accuracy, and reliability of a non-invasive 3-Tesla magnetic resonance imaging technique (3 T-MRI) for the visualization of maxillary sinus grafts in comparison to conventional, X-ray-based, established standard imaging techniques. METHODS: A total of eight patients with alveolar bone atrophy who required surgical sinus floor augmentation in the course of dental implantation were included in this pilot study. Alongside pre-operative cone-beam computed tomography (CBCT), 3 T-MRI was performed before and 6 months after sinus floor augmentation. Two investigators measured the maxillary sinus volume preoperatively and after bone augmentation. RESULTS: In all cases, MRI demonstrated accurately the volumes of the maxillary sinus grafts. Following surgery, the bony structures suitable for an implant placement increased at an average of 4.89 cm3, corresponding with the decrease of the intrasinusidal volumes. In general, interexaminer discrepancies were low and without statistical significance. CONCLUSION: In this preliminary study, we could demonstrate the feasibility of MRI bone volume measurement as a radiation-free alternative with comparable accuracy to CT/CBCT before procedures like sinus floor augmentation. Nevertheless, costs and artifacts, also present in MRI, have to be taken into account. Larger studies will be necessary to justify the practicability of MRI bone volume evaluation.


Assuntos
Implantes Dentários , Levantamento do Assoalho do Seio Maxilar , Humanos , Implantação Dentária Endóssea/métodos , Levantamento do Assoalho do Seio Maxilar/métodos , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/cirurgia , Projetos Piloto , Reprodutibilidade dos Testes , Transplante Ósseo/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Imageamento por Ressonância Magnética , Maxila/cirurgia
2.
Gynecol Oncol ; 173: 58-67, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37086524

RESUMO

BACKGROUND: Despite evidence supporting its use, many Enhanced Recovery After Surgery (ERAS) recommendations remain poorly adhered to and barriers to ERAS implementation persist. In this second updated ERAS® Society guideline, a consensus for optimal perioperative care in gynecologic oncology surgery is presented, with a specific emphasis on implementation challenges. METHODS: Based on the gaps identified by clinician stakeholder groups, nine implementation challenge topics were prioritized for review. A database search of publications using Embase and PubMed was performed (2018-2023). Studies on each topic were selected with emphasis on meta-analyses, randomized controlled trials, and large prospective cohort studies. These studies were then reviewed and graded by an international panel according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. RESULTS: All recommendations on ERAS implementation challenge topics are based on best available evidence. The level of evidence for each item is presented accordingly. CONCLUSIONS: The updated evidence base and recommendations for stakeholder derived ERAS implementation challenges in gynecologic oncology are presented by the ERAS® Society in this consensus review.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Neoplasias dos Genitais Femininos , Feminino , Humanos , Neoplasias dos Genitais Femininos/cirurgia , Estudos Prospectivos , Assistência Perioperatória , Procedimentos Cirúrgicos em Ginecologia
3.
Rev. otorrinolaringol. cir. cabeza cuello ; 82(3): 366-370, sept. 2022. ilus
Artigo em Espanhol | LILACS | ID: biblio-1409948

RESUMO

Resumen El quiste epidérmico es una lesión benigna y común de la piel. Se desarrolla por un bloqueo de la unidad pilosebácea, con la consecuente proliferación de células epiteliales y secuestro de queratina. El 7% se desarrollan en cabeza y cuello, sin embargo, son infrecuentes en canal auditivo externo. Su patrón de crecimiento es lento y progresivo durante años, siendo asintomáticos. Al aumentar de tamaño causan sintomatología variable, acorde a su localización; en el canal auditivo tienen un comportamiento obstructivo que genera síntomas como otalgia e hipoacusia. Se presenta caso de una paciente de 69 años, con acúfeno e hipoacusia progresiva derecha. Durante la otoscopia se observó una neoformación obstructiva del 100% de la luz del conducto. Se realizaron estudios de imagen que reportaron tumoración de características quísticas de conducto auditivo derecho, bien circunscrita, sin erosión ósea. Para el diagnóstico definitivo, se realizó resección quirúrgica y biopsia reportando quiste epidérmico. Durante el seguimiento posoperatorio sin hallazgos de recidiva.


Abstract The epidermal cyst is a common and benign lesion of the skin. It develops due to a blockage of the pilosebaceous unit, with the consequent proliferation of epithelial cells and keratin sequestration. Seven percent develop in the head and neck; however, they are infrequent in the external auditory canal. Its growth pattern is slow and progressive over the years, being asymptomatic. As they increase in size, they cause variable symptoms, according to their location. In the ear canal they have an obstructive behavior that generates symptoms such as earache and hearing loss. A case of a 69-year-old female with tinnitus and progressive right hearing loss is presented. At otoscopy, a 100% obstructive neoformation of the canal lumen was observed. Imaging studies showed a well circumscribed, cystic tumor of the right ear canal, without bone erosion. For the definitive diagnosis, a resection and biopsy were performed, reporting an epidermal cyst. During follow up there was no recurrence of tumor.


Assuntos
Humanos , Feminino , Idoso , Meato Acústico Externo/diagnóstico por imagem , Otopatias/diagnóstico por imagem , Cisto Epidérmico/diagnóstico por imagem , Neoplasias da Orelha/diagnóstico por imagem , Meato Acústico Externo/cirurgia , Otopatias/cirurgia , Otopatias/patologia , Cisto Epidérmico/cirurgia , Cisto Epidérmico/patologia
5.
Gynecol Oncol ; 161(1): 46-55, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33388155

RESUMO

OBJECTIVE: To assess the benefit of Enhanced Recovery After Surgery (ERAS) on length of stay (LOS), postoperative complications, 30-day readmission, and cost in gynecologic oncology. METHODS: A systematic literature search was performed in MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science for all peer-reviewed cohort studies and controlled trials on ERAS involving gynecologic oncology patients. Abstracts, commentaries, non-controlled studies, and studies without specific data on gynecologic oncology patients were excluded. Meta-analysis was performed on the primary endpoint of LOS. Subgroup analyses were performed based on risk of bias of the studies included, number of ERAS elements, and ERAS compliance. Secondary endpoints were readmission rate, complications, and cost. RESULTS: A total of 31 studies (6703 patients) were included: 5 randomized controlled trials, and 26 cohort studies. Meta-analysis of 27 studies (6345 patients) demonstrated a decrease in LOS of 1.6 days (95% confidence interval, CI 1.2-2.1) with ERAS implementation. Meta-analysis of 21 studies (4974 patients) demonstrated a 32% reduction in complications (OR 0.68, 95% CI 0.55-0.83) and a 20% reduction in readmission (OR 0.80, 95% CI 0.64-0.99) for ERAS patients. There was no difference in 30-day postoperative mortality (OR 0.61, 95% CI 0.23-1.6) for ERAS patients compared to controls. No difference in the odds of complications or reduction in LOS was observed based on number of included ERAS elements or reported compliance with ERAS interventions. The mean cost savings for ERAS patients was $2129 USD (95% CI $712 - $3544). CONCLUSIONS: ERAS protocols decrease LOS, complications, and cost without increasing rates of readmission or mortality in gynecologic oncology surgery. This evidence supports implementation of ERAS as standard of care in gynecologic oncology.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Neoplasias dos Genitais Femininos/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Procedimentos Cirúrgicos de Citorredução/normas , Feminino , Procedimentos Cirúrgicos em Ginecologia/métodos , Procedimentos Cirúrgicos em Ginecologia/normas , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
6.
J Fr Ophtalmol ; 42(9): 951-958, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31248610

RESUMO

INTRODUCTION: While surgery for small macular holes (<400µm) is well-described, the results are not as clear-cut for larger holes (>400µm). Our purpose is to demonstrate the difference in terms of closure and final visual acuity between 3 techniques: the classical technique, the FLAP technique and internal limiting membrane (ILM) transfer. METHODS: This retrospective non-randomized study included consecutive patients with a macular hole greater than 400µm. Myopic eyes (>26.5mm or >6.50D) and eyes with other retinal comorbidities were excluded. All patients underwent pars plana vitrectomy in combination with one of the 3 techniques. RESULTS: We included 84 eyes of 77 patients between 2005 and 2018; 57 in the classic group (A), 13 in the FLAP group (B) and 14 in the ILM transfer group (C). The closure rate at 3 months was 70.18 % in group A, 100 % in group B and 92.86 % in group C. The closure rate was significantly higher in group B and C compared to group A. There was no significant improvement between pre- and post-operative best corrected visual acuity in any group. The gain in BCVA was 2.90 lines (±2.98) in group A, 3.40 lines (±2.40) in group B, and 1.07 lines (±1.04) in group C. The gain was significantly lower in group C compared to group A and B. CONCLUSION: ILM interposition appears to offer a true anatomical advantage for closing large holes, but the functional recovery does not appear to be better or worse.


Assuntos
Membrana Epirretiniana/cirurgia , Perfurações Retinianas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Oftalmológicos/métodos , Recuperação de Função Fisiológica , Perfurações Retinianas/patologia , Perfurações Retinianas/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual
7.
J Clin Virol ; 110: 36-41, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30530097

RESUMO

BACKGROUND: HIV-1 viral load testing is now recommended by the World Health Organization for every patient receiving antiretroviral therapy (ART). OBJECTIVES: The objective of this study is to evaluate the performance of commercial assays for their ability to quantify HIV-1 strains currently circulating in France. STUDY DESIGN: The performances of the Generic HIV-RNA assay from Biocentric were compared to those of the Roche CAP/CTM v1.5, Roche CAP/CTM v2.0 and Abbott m2000 RealTime HIV-1 assays. A total of 1885 HIV-1 plasma samples were tested, including 684 samples from patients included in the ANRS-Primo Cohort. RESULTS: We found a good concordance of quantification between the Roche v2.0 and the Biocentric assays, both of which were superior to the Roche v1.5 assay. We show moderate agreement between techniques; however, CRF02_AG strains and undetermined viruses were underestimated when quantified with the Roche CAP/CTM v2.0. In contrast, a comparison of the Biocentric and Abbott assay results showed strong agreement between assays, indicating that both are well suited for quantification of CRF02_AG strains. Moreover, a 2% underestimation of the B subtypes was observed with the Biocentric assay. CONCLUSIONS: These results have implications for viral load monitoring in Western Africa, where CRF02_AG strains are highly prevalent. Closer epidemiological surveillance and evaluation of commercial assays are still necessary to better evaluate the impact of the genetic evolution of circulating viruses on HIV-RNA quantification in the regions most affected by the HIV-1 epidemic.


Assuntos
Técnicas de Laboratório Clínico/métodos , Infecções por HIV/diagnóstico , HIV-1/classificação , RNA Viral/sangue , Carga Viral/métodos , Estudos de Coortes , França , Infecções por HIV/virologia , Soropositividade para HIV/diagnóstico , Humanos , Programas de Rastreamento , RNA Viral/genética , Sensibilidade e Especificidade
8.
Ophthalmologe ; 115(1): 12-20, 2018 01.
Artigo em Alemão | MEDLINE | ID: mdl-28289879

RESUMO

BACKGROUND: The objective of the study was to examine the predictability of residual astigmatism after cataract surgery and implantation of the posterior chamber aspheric toric lens TECNIS® ZCT, Abott Medical Optic (Ettlingen, Deutschland). MATERIAL AND METHODS: The retrospective study included a total of 88 patient eyes undergoing a cataract operation with a toric lens implantation between March 2014 and October 2015. The inclusion criteria were a regular astigmatism of at least 0.75 dpt. Posterior chamber toric lenses (model Tecnis ZCT) were exclusively implanted. Post-surgery check-ups were performed after 1 day, 1 month and 2 months. Main study outcome was best-corrected visual acuity (BCVA), spherical and astigmatic aberration and the difference between expected and actual residual astigmatism after cataract surgery. RESULTS: The median reduction of corneal astigmatism was from -2.50 dpt (±1.06 dpt) to -0.75 dpt (±0.51 dpt) (p ≤ 0.05). The median BCVA increased from 0.37 logMAR (±0.25 logMAR) before surgery to 0.09 logMAR (±0.10 logMAR) after surgery. The spherical equivalent was reduced from +3.50 dpt (±1.11 dpt) (presurgery) to -0.56 dpt (±0.51 dpt) (postsurgery) in hyperopic patients and from -2.44 dpt (±3.03 dpt) to -0.69 dpt (±0.81 dpt) in myopic patients. By using the power vector analysis no significant deviation from the expected target values was observed; however, the median discrepancy between the expected and actual residual astigmatism was -0.50 dpt despite a surgical orientation of the intraocular lens (IOL) within 5° of the desired axis. The IOL showed a median rotation of 3.00° (±4.46°). CONCLUSION: Implantation of the aspheric toric intraocular lens Tecnis ZCT is a predictable, effective and reproducible tool in cataract surgery to account for regular corneal astigmatis; however, despite an optimal surgical orientation of the toric IOL, a small and rarely a large discrepancy might occur between expected and actual residual astigmatism.


Assuntos
Astigmatismo , Catarata , Lentes Intraoculares , Facoemulsificação , Humanos , Implante de Lente Intraocular , Estudos Prospectivos , Refração Ocular , Estudos Retrospectivos , Acuidade Visual
9.
J Neuroendocrinol ; 30(2)2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29265686

RESUMO

The neurosteroid allopregnanolone (AP) modulates neuroendocrine/neurobiological processes, including hypothalamic-pituitary-adrenocortical activities, pain, anxiety, neurogenesis and neuroprotection. These observations raised the hope of developing AP-based therapies against neuroendocrine and/or neurodegenerative disorders. However, the pleiotropic actions of AP, particularly its cell-proliferation-promoting effects, hamper the development of selective/targeted therapies. For example, although AP-induced neurogenesis may serve to compensate neuronal loss in degenerative brains, AP-evoked cell-proliferation is contraindicated for steroid-sensitive cancer patients. To foster progress, we synthesised 4 novel AP analogues of neurosteroids (ANS) designated BR053 (12-oxo-epi-AP), BR297 (O-allyl-epi-AP), BR351 (O-allyl-AP) and BR338 (12-oxo-AP). First, because AP is well-known as allosteric modulator of GABAA receptors (GABAA-R), we used the electrophysiological patch-clamp technique to determine the structure-activity relationship of our ANS on GABAA-activated current in NCB20 cells expressing functional GABAA-R. We found that the addition of 12-oxo-group did not significantly change the respective positive or negative allosteric effects of 3α-AP or 3ß-(epi)-AP analogues. Importantly, substitution of the 3α-hydroxyl-group by 3α-O-allyl highly modified the ANS activities. Unlike AP, BR351 induced a long-lasting desensitisation/inhibition of GABAA-R. Interestingly, replacement of the 3ß-hydroxyl by 3ß-O-allyl (BR297) completely reversed the activity from negative to positive allosteric action. In a second step, we compared the actions of AP and ANS on SH-SY5Y neuronal cell viability/proliferation using MTT-reduction assays. Different dose-response curves were demonstrated for AP and the ANS. By contrast to AP, BR297 was totally devoid of cell-proliferative effect. Finally, we compared AP and ANS abilities to protect against oxidative stress-induced neuronal death pivotally involved in neurodegenerative diseases. Both BR351 and BR297 had notable advantages over AP in protecting SH-SY5Y cells against oxidative stress-induced death. Thus, BR297 appears to be a potent neuroprotective compound devoid of cell-proliferative activity. Altogether, our results suggest promising perspectives for the development of neurosteroid-based selective and effective strategies against neuroendocrine and/or neurodegenerative disorders.


Assuntos
Encéfalo/metabolismo , Neurônios/metabolismo , Neurotransmissores/metabolismo , Pregnanolona/metabolismo , Receptores de GABA-A/metabolismo , Animais , Linhagem Celular , Camundongos , Conformação Proteica
10.
Rev Epidemiol Sante Publique ; 66(1): 7-17, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29233572

RESUMO

BACKGROUND: In a context of the evolution of severe morbidities in patients living with HIV (PLWH), the aim of this study was to describe reasons for hospitalization and the mode of care for the patients requiring hospitalization. METHODS: All admissions (≥24h) of PLWH to 10 hospitals in the south of Paris (COREVIH Ile-de-France Sud) between 1/1/2011 and 12/31/2011 were identified. The hospital database and the file of patients followed in the HIV referral department of each hospital were matched. Detailed clinical and biological data were collected, by returning to the individual medical records, for a random sample (65% of hospitalized patients). RESULTS: A total of 3013 hospitalizations (1489 patients) were recorded in 2011. The estimated rate of hospitalized patients was about 8% among the 10105 PLWH routinely managed in COREVIH Ile-de-France Sud in 2011. The majority (58.5%) of these hospitalizations occurred in a unit other than the HIV referral unit. Non-AIDS-defining infections were the main reason for admission (16.4%), followed by HIV-related diseases (15.6%), hepatic/gastrointestinal diseases (12.0%), and cardiovascular diseases (10.3%). The median length of stay was 5 days overall (IQR: 2-11), it was longer among patients admitted to a referral HIV care unit than to another ward. HIV infection had been diagnosed >10 years previously in 61.4% of these hospitalized patients. They often had associated comorbidities (coinfection HCV/HVB 40.5%, smoking 45.8%; hypertension 33.4%, dyslipidemia 28.8%, diabetes 14.8%). Subjects over 60 years old accounted for 15% of hospitalized patients, most of them were virologically controlled under HIV treatment, and cardiovascular diseases were their leading reason for admission. CONCLUSION: Needs for hospitalization among PLWH remain important, with a wide variety in causes of admission, involving all hospital departments. It is essential to prevent comorbidities to reduce these hospitalizations, and to maintain a link between the management of PLWH, that becomes rightly, increasing ambulatory, and recourse to specialized inpatient services.


Assuntos
Atenção à Saúde/estatística & dados numéricos , Infecções por HIV/epidemiologia , Necessidades e Demandas de Serviços de Saúde , Hospitalização/estatística & dados numéricos , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Adulto , Comorbidade , Atenção à Saúde/normas , Feminino , Infecções por HIV/complicações , HIV-1 , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Necessidades e Demandas de Serviços de Saúde/tendências , Departamentos Hospitalares/estatística & dados numéricos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Paris/epidemiologia , Adulto Jovem
12.
Leukemia ; 31(12): 2568-2576, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28484265

RESUMO

While outcomes for children with T-cell acute lymphoblastic leukemia (T-ALL) have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid (GC) resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor (ETP) T-ALLs as well as in a subset of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 (IL7) stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Glucocorticoides/farmacologia , Interleucina-7/metabolismo , Janus Quinases/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Antineoplásicos/uso terapêutico , Proteína 11 Semelhante a Bcl-2/metabolismo , Linhagem Celular Tumoral , Dexametasona/farmacologia , Modelos Animais de Doenças , Humanos , Inibidores de Janus Quinases/farmacologia , Camundongos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Leukemia ; 31(11): 2365-2375, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28331226

RESUMO

Leukemias bearing CRLF2 and JAK2 gene alterations are characterized by aberrant JAK/STAT signaling and poor prognosis. The HDAC inhibitor givinostat/ITF2357 has been shown to exert anti-neoplastic activity against both systemic juvenile idiopathic arthritis and myeloproliferative neoplasms through inhibition of the JAK/STAT pathway. These findings led us to hypothesize that givinostat might also act against CRLF2-rearranged BCP-ALL, which lack effective therapies. Here, we found that givinostat inhibited proliferation and induced apoptosis of BCP-ALL CRLF2-rearranged cell lines, positive for exon 16 JAK2 mutations. Likewise, givinostat killed primary cells, but not their normal hematopoietic counterparts, from patients carrying CRLF2 rearrangements. At low doses, givinostat downregulated the expression of genes belonging to the JAK/STAT pathway and inhibited STAT5 phosphorylation. In vivo, givinostat significantly reduced engraftment of human blasts in patient-derived xenograft models of CRLF2-positive BCP-ALL. Importantly, givinostat killed ruxolitinib-resistant cells and potentiated the effect of current chemotherapy. Thus, givinostat in combination with conventional chemotherapy may represent an effective therapeutic option for these difficult-to-treat subsets of ALL. Lastly, the selective killing of cancer cells by givinostat may allow the design of reduced intensity regimens in CRLF2-rearranged Down syndrome-associated BCP-ALL patients with an overall benefit in terms of both toxicity and related complications.


Assuntos
Carbamatos/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Receptores de Citocinas/genética , Adolescente , Animais , Linhagem Celular Tumoral , Pré-Escolar , Feminino , Humanos , Masculino , Camundongos , Nitrilas , Fosforilação , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pirazóis/farmacologia , Pirimidinas , Fator de Transcrição STAT5/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Behav Brain Res ; 320: 440-449, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-27789344

RESUMO

The antineoplastic oxaliplatin (OXAL) is pivotal for metastatic cancer treatments. However, OXAL evokes sensory and motor side-effects including pain, muscle weakness, motor nerve fiber dysfunctions/neuropathies that significantly impact patients' lives. Therefore, preclinical investigations are struggling to characterize effective analgesics against OXAL-induced painful/sensory symptoms but surprisingly, OXAL-evoked motor dysfunctions received little attention although these neurological symptoms are also disabling for patients. Here, we validated a rat model of OXAL-induced motor neuropathy by using (i) behavioral methods as the wire suspension and balance beam tests to assess muscle weakness and (ii) electrophysiological techniques to record the gastrocnemius electromyography (EMG). The conductance velocity of motor fibers was reduced and compound muscle action potential (CMAP) duration increased in OXAL-treated rats, leading to CMAP dispersion with no modification of the area under the curve, reflecting a heterogeneous demyelination of motor fibers. Functional motor unit analysis revealed a 50 % decrease of their estimated number which was compensated by a motor unit size increase. OXAL-induced motor weakness appeared as a combined consequence of motor fiber demyelination and motor axonopathy. Because we previously observed that allopregnanolone (AP) counteracted OXAL-evoked painful/sensory symptoms, we evaluated its action against OXAL-induced motor neurological dysfunctions. AP treatment successfully corrected motor behaviors, conductance velocity, CMAP duration, motor unit number (MUN) and motor unit size altered by OXAL-chemotherapy. These results, which are the first to show that AP efficiently rescues OXAL-induced motor neuropathy, consolidate the idea that AP-based therapy may be relevant for the treatment of both sensory and motor peripheral neuropathies.


Assuntos
Anestésicos/uso terapêutico , Antineoplásicos/toxicidade , Potencial Evocado Motor/efeitos dos fármacos , Transtornos Motores , Compostos Organoplatínicos/toxicidade , Pregnanolona/uso terapêutico , Acetilcolinesterase/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Transtornos Motores/induzido quimicamente , Transtornos Motores/tratamento farmacológico , Transtornos Motores/fisiopatologia , Força Muscular/efeitos dos fármacos , Condução Nervosa/efeitos dos fármacos , Oxaliplatina , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
15.
Leukemia ; 30(6): 1246-54, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26847027

RESUMO

Precursor-B-cell receptor (pre-BCR) signaling and spleen tyrosine kinase (SYK) recently were introduced as therapeutic targets for patients with B-cell acute lymphoblastic leukemia (B-ALL), but the importance of this pathway in B-ALL subsets and mechanism of downstream signaling have not fully been elucidated. Here, we provide new detailed insight into the mechanism of pre-BCR signaling in B-ALL. We compared the effects of pharmacological and genetic disruption of pre-BCR signaling in vitro and in mouse models for B-ALL, demonstrating exquisite dependency of pre-BCR(+) B-ALL, but not other B-ALL subsets, on this signaling pathway. We demonstrate that SYK, PI3K/AKT, FOXO1 and MYC are important downstream mediators of pre-BCR signaling in B-ALL. Furthermore, we define a characteristic immune phenotype and gene expression signature of pre-BCR(+) ALL to distinguish them from other B-ALL subsets. These data provide comprehensive new insight into pre-BCR signaling in B-ALL and corroborate pre-BCR signaling and SYK as promising new therapeutic targets in pre-BCR(+) B-ALL.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Células Precursoras de Linfócitos B/química , Receptores de Antígenos de Linfócitos B/metabolismo , Transdução de Sinais , Animais , Linhagem Celular , Proteína Forkhead Box O1/metabolismo , Xenoenxertos , Humanos , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Quinase Syk/metabolismo
17.
Cell Death Dis ; 7: e2052, 2016 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-26775704

RESUMO

SMAC-mimetics represent a targeted therapy approach to overcome apoptosis resistance in many tumors. Here, we investigated the efficacy of the SMAC-mimetic BV6 in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In ALL cell lines, intrinsic apoptosis sensitivity was associated with rapid cIAP degradation, NF-κB activation, TNF-α secretion and induction of an autocrine TNF-α-dependent cell death loop. This pattern of responsiveness was also observed upon ex vivo analysis of 40 primograft BCP-ALL samples. Treatment with BV6 induced cell death in the majority of ALL primografts including leukemias with high-risk and poor-prognosis features. Inhibition of cell death by the TNF receptor fusion protein etanercept demonstrated that BV6 activity is dependent on TNF-α. In a preclinical NOD/SCID/huALL model of high-risk ALL, marked anti-leukemia effectivity and significantly prolonged survival were observed upon BV6 treatment. Interestingly, also in vivo, intrinsic SMAC-mimetic activity was mediated by TNF-α. Importantly, BV6 increased the effectivity of conventional induction therapy including vincristine, dexamethasone and asparaginase leading to prolonged remission induction. These data suggest SMAC-mimetics as an important addendum to efficient therapy of pediatric BCP-ALL.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Apoptose , Morte Celular , Linhagem Celular Tumoral , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Fatores de Risco , Transdução de Sinais
18.
Ann Oncol ; 27(2): 306-14, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26598546

RESUMO

BACKGROUND: ALK-negative anaplastic large cell lymphoma associated with breast implant (i-ALCL) has been recently recognized as a distinct entity. Among 43 830 lymphomas registered in the French Lymphopath network since 2010, 300 breast lymphomas comprising 25 peripheral T-cell lymphomas (PTCL) were reviewed. Among PTCL, ALK-negative ALCL was the most frequent and all of them were associated with breast implants. PATIENTS AND METHODS: Since 2010, all i-ALCL cases were collected from different institutions through Lymphopath. Immuno-morphologic features, molecular data and clinical outcome of 19 i-ALCLs have been retrospectively analyzed. RESULTS: The median age of the patients was 61 years and the median length between breast implant and i-ALCL was 9 years. Most implants were silicone-filled and textured. Implant removal was performed in 17 out of 19 patients with additional treatment based on mostly CHOP or CHOP-like chemotherapy regimens (n = 10/19) or irradiation (n = 1/19). CHOP alone or ABVD following radiation without implant removal have been given in two patients. The two clinical presentations, i.e. effusion and less frequently tumor mass correlated with distinct histopathologic features: in situ i-ALCL (anaplastic cell proliferation confined to the fibrous capsule) and infiltrative i-ALCL (pleomorphic cells massively infiltrating adjacent tissue with eosinophils and sometimes Reed-Sternberg-like cells mimicking Hodgkin lymphoma). Malignant cells were CD30-positive, showed a variable staining for EMA and were ALK negative. Most cases had a cytotoxic T-cell immunophenotype with variable T-cell antigen loss and pSTAT3 nuclear expression. T-cell receptor genes were clonally rearranged in 13 out of 13 tested cases. After 18 months of median follow-up, the 2-year overall survival for in situ and infiltrative i-ALCL was 100% and 52.5%, respectively. CONCLUSIONS: In situ i-ALCLs have an indolent clinical course and generally remain free of disease after implant removal. However, infiltrative i-ALCLs could have a more aggressive clinical course that might require additional therapy to implant removal.


Assuntos
Implantes de Mama/efeitos adversos , Linfoma Anaplásico de Células Grandes/patologia , Linfoma de Células T Periférico/patologia , Silicones/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico , Feminino , Doença de Hodgkin/patologia , Humanos , Imunofenotipagem , Antígeno Ki-1/metabolismo , Linfoma Anaplásico de Células Grandes/induzido quimicamente , Linfoma Anaplásico de Células Grandes/mortalidade , Linfoma de Células T Periférico/induzido quimicamente , Linfoma de Células T Periférico/mortalidade , Pessoa de Meia-Idade , Receptores Proteína Tirosina Quinases/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Estudos Retrospectivos , Fator de Transcrição STAT3/metabolismo , Linfócitos T Citotóxicos/imunologia
20.
Ann Dermatol Venereol ; 142(11): 664-9, 2015 Nov.
Artigo em Francês | MEDLINE | ID: mdl-26372545

RESUMO

BACKGROUND: The association of pyoderma gangrenosum (PG) with colonic diverticulitis infection (DI) is relatively unknown. Herein, we describe two cases of PG with full recovery after colonic surgery. PATIENTS AND METHODS: Case 1: an 83-year-old man presented with lesions on his legs that had been present for several weeks, and a diagnosis of PG was confirmed histologically. Abdominopelvic computed tomography (CT) performed on account of biological inflammatory syndrome revealed DI complicated by abscesses. Following the failure of two different antibiotic regimens, sigmoidectomy was performed. Postoperatively, the skin lesions healed without local or systemic corticosteroids. Case 2: a 63-year-old woman presented PG resistant to local and systemic corticosteroids and dapsone for several months. A particularly severe flare was accompanied by abdominal pain and inflammatory syndrome. CT revealed perforated sigmoid DI. Sigmoidectomy was performed after failure of drug therapy. The patient's PG subsequently improved and had disappeared without recurrence at 24months. DISCUSSION: Both of these cases of PG revealed DI. The hypothesis is that DI constituted a source of colonic inflammation, sending out bacterial antigenic stimuli that resulted in PG through deposition of circulating immune complexes. Removal of this inflammatory source appears to have enabled healing of PG. CONCLUSION: DI must be added to the list of systemic diseases associated with PG. In the case of isolated PG, CT may be used to detect asymptomatic DI. Early diagnosis could prevent serious gastrointestinal complications.


Assuntos
Doença Diverticular do Colo/complicações , Doença Diverticular do Colo/diagnóstico , Pioderma Gangrenoso/diagnóstico , Pioderma Gangrenoso/etiologia , Idoso de 80 Anos ou mais , Colectomia , Colo Sigmoide/patologia , Doença Diverticular do Colo/cirurgia , Feminino , Mãos/patologia , Humanos , Perna (Membro)/patologia , Masculino , Pessoa de Meia-Idade , Remissão Espontânea , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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