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1.
AJNR Am J Neuroradiol ; 44(6): 730-739, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37202114

RESUMO

BACKGROUND: Spontaneous intracranial hypotension is an important cause of treatable secondary headaches. Evidence on the efficacy of epidural blood patching and surgery for spontaneous intracranial hypotension has not been synthesized. PURPOSE: Our aim was to identify evidence clusters and knowledge gaps in the efficacy of treatments for spontaneous intracranial hypotension to prioritize future research. DATA SOURCES: We searched published English language articles on MEDLINE (Ovid), the Web of Science (Clarivate), and EMBASE (Elsevier) from inception until October 29, 2021. STUDY SELECTION: We reviewed experimental, observational, and systematic review studies assessing the efficacy of epidural blood patching or surgery in spontaneous intracranial hypotension. DATA ANALYSIS: One author performed data extraction, and a second verified it. Disagreements were resolved by consensus or adjudicated by a third author. DATA SYNTHESIS: One hundred thirty-nine studies were included (median, 14 participants; range, 3-298 participants). Most articles were published in the past decade. Most assessed epidural blood patching outcomes. No studies met level 1 evidence. Most were retrospective cohort or case series (92.1%, n = 128). A few compared the efficacy of different treatments (10.8%, n = 15). Most used objective methods for the diagnosis of spontaneous intracranial hypotension (62.3%, n = 86); however, 37.7% (n = 52) did not clearly meet the International Classification of Headache Disorders-3 criteria. CSF leak type was unclear in 77.7% (n = 108). Nearly all reported patient symptoms using unvalidated measures (84.9%, n = 118). Outcomes were rarely collected at uniform prespecified time points. LIMITATIONS: The investigation did not include transvenous embolization of CSF-to-venous fistulas. CONCLUSIONS: Evidence gaps demonstrate a need for prospective study designs, clinical trials, and comparative studies. We recommend using the International Classification of Headache Disorders-3 diagnostic criteria, explicit reporting of CSF leak subtype, inclusion of key procedural details, and using objective validated outcome measures collected at uniform time points.


Assuntos
Transtornos da Cefaleia , Hipotensão Intracraniana , Humanos , Hipotensão Intracraniana/complicações , Hipotensão Intracraniana/diagnóstico , Hipotensão Intracraniana/terapia , Estudos Retrospectivos , Estudos Prospectivos , Placa de Sangue Epidural/métodos , Cefaleia/etiologia , Transtornos da Cefaleia/complicações
2.
AJNR Am J Neuroradiol ; 44(5): 618-622, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37080723

RESUMO

BACKGROUND AND PURPOSE: Wrong-level spinal surgery, especially in the thoracic spine, remains a challenge for a variety of reasons related to visualization, such as osteopenia, large body habitus, severe kyphosis, radiographic misinterpretation, or anatomic variation. Preoperative fiducial marker placement performed in a dedicated imaging suite has been proposed to facilitate identification of thoracic spine vertebral levels. In this current study, we report our experience using image-guided percutaneous gold fiducial marker placement to enhance the accuracy and safety of thoracic spinal surgical procedures. MATERIALS AND METHODS: A retrospective review was performed of all fluoroscopy- or CT-guided gold fiducial markers placed at our institution between January 3, 2019, and March 16, 2022. A chart review of 179 patients was performed detailing the procedural approach and clinical information. In addition, the method of gold fiducial marker placement (fluoroscopy/CT), procedure duration, spinal level of the gold fiducial marker, radiation dose, fluoroscopy time, surgery date, and complications (including whether wrong-level surgery occurred) were recorded. RESULTS: A total of 179 patients (104 female) underwent gold fiducial marker placement. The mean age was 57 years (range, 12-96 years). Fiducial marker placement was performed by 13 different neuroradiologists. All placements were technically successful without complications. All 179 (100%) operations were performed at the correct level. Most fiducial markers (143) were placed with fluoroscopy with the most common location at T6-T8. The most common location for placement in CT was at T3 and T4. CONCLUSIONS: All operations guided with gold fiducial markers were performed at the correct level. There were no complications of fiducial marker placement.


Assuntos
Marcadores Fiduciais , Ouro , Humanos , Feminino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/cirurgia , Fluoroscopia/métodos
3.
Rhinology ; 61(2): 124-131, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36480330

RESUMO

BACKGROUND: Several studies have demonstrated the association between chronic rhinosinusitis (CRS) and autoimmune diseases. However, there are few long-term longitudinal studies on this relationship. Therefore, we investigated the association between CRS and the risk of a subgroup of autoimmune disease using a representative nationwide cohort sample. METHODOLOGY: We investigated the association between CRS and autoimmune diseases, including Sjogren's syndrome, systemic lupus erythematosus, and ankylosing spondylitis. A total of 15,130 CRS patients and 30,260 patients without CRS were enrolled after 1:2 propensity score matching. A Cox proportional hazards model was used to analyse the hazard ratio (HR) of CRS for autoimmune disease. RESULTS: The incidence of Sjogren's syndrome, systemic lupus erythematosus, and ankylosing spondylitis was 0.55, 0.10, and 0.48 per 1000 person-years, respectively. Among autoimmune diseases, the risk of Sjogren's syndrome in CRS patients was significantly increased to an adjusted HR (aHR) of 1.70, whereas we could not detect any significant risk of developing systemic lupus erythematosus or ankylosing spondylitis. In the subgroup analysis according to CRS phenotype, the adjusted HR of developing Sjogren's syndrome was greater in CRS patients without nasal polyps) than in CRS patients with nasal polyps. CONCLUSIONS: Our study suggests that CRS without nasal polyps is associated with an increased incidence of Sjogren's syndrome diagnosis compared to CRS without nasal polyps. Additionally, there was no association between CRS and systemic lupus erythematosus or ankylosing spondylitis, regardless of CRS phenotype.


Assuntos
Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Pólipos Nasais , Síndrome de Sjogren , Espondilite Anquilosante , Humanos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/epidemiologia , Síndrome de Sjogren/genética , Espondilite Anquilosante/complicações , Espondilite Anquilosante/epidemiologia , Pólipos Nasais/complicações , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/genética , Doenças Autoimunes/complicações , Doença Crônica
4.
AJNR Am J Neuroradiol ; 43(1): 117-124, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34887246

RESUMO

BACKGROUND AND PURPOSE: Percutaneous CT-guided core needle biopsies of head and neck lesions can be safely performed with vigilant planning. This largest-to-date single-center retrospective study evaluates multiple approaches with consideration of special techniques and examines the histopathologic yield. MATERIALS AND METHODS: Retrospective review of CT-guided core biopsies of head and neck lesions from January 1, 2010, to October 30, 2020, was performed. We recorded the following: patient demographics, sedation details, biopsy needle type and size, lesion location and size, approach, patient positioning, preprocedural intravenous contrast, proceduralists' years of experience, complications, and pathology results. RESULTS: One hundred eighty-four CT-guided core biopsies were evaluated. The initial diagnostic yield was 93% (171/184). However, of 43/184 (23%) originally "negative for malignancy" biopsies, 4 were eventually positive for malignancy via rebiopsy/excision, resulting in a 2% false-negative rate and an adjusted total diagnostic yield of 167/184 (91%). Biopsies were performed by 16 neuroradiologists with variable experience. The diagnostic yield was essentially the same: 91% (64/70) for proceduralists with ≤3 years' experience, and 90% (103/114) with >3 years' experience. The diagnostic yield was 93% (155/166) for lesions of >10 mm. The diagnostic yield per biopsy needle gauge was the following: 20 ga, 81% (13/16); 18 ga, 93% (70/75); 16 ga, 90% (64/71); and 14 ga, 91% (20/22). There were 4 asymptomatic hematomas, with none requiring intervention. CONCLUSIONS: Percutaneous CT-guided core needle biopsies are safe procedures for superficial and deep head and neck lesions with a high diagnostic yield. Careful planning and special techniques may increase the number of lesions accessible percutaneously while minimizing the risk of complications.


Assuntos
Biópsia Guiada por Imagem , Tomografia Computadorizada por Raios X , Biópsia com Agulha de Grande Calibre/efeitos adversos , Biópsia com Agulha de Grande Calibre/métodos , Humanos , Biópsia Guiada por Imagem/métodos , Pescoço , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
5.
Sci Rep ; 11(1): 3639, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574475

RESUMO

Myelomeningocele (MMC) affects one in 1000 newborns annually worldwide and each surviving child faces tremendous lifetime medical and caregiving burdens. Both genetic and environmental factors contribute to disease risk but the mechanism is unclear. This study examined 506 MMC subjects for ultra-rare deleterious variants (URDVs, absent in gnomAD v2.1.1 controls that have Combined Annotation Dependent Depletion score ≥ 20) in candidate genes either known to cause abnormal neural tube closure in animals or previously associated with human MMC in the current study cohort. Approximately 70% of the study subjects carried one to nine URDVs among 302 candidate genes. Half of the study subjects carried heterozygous URDVs in multiple genes involved in the structure and/or function of cilium, cytoskeleton, extracellular matrix, WNT signaling, and/or cell migration. Another 20% of the study subjects carried heterozygous URDVs in candidate genes associated with gene transcription regulation, folate metabolism, or glucose metabolism. Presence of URDVs in the candidate genes involving these biological function groups may elevate the risk of developing myelomeningocele in the study cohort.


Assuntos
Deleção de Genes , Predisposição Genética para Doença , Meningomielocele/genética , Defeitos do Tubo Neural/genética , Movimento Celular/genética , Cílios/genética , Citoesqueleto/genética , Matriz Extracelular/genética , Feminino , Estudos de Associação Genética , Humanos , Masculino , Meningomielocele/patologia , Fatores de Risco , Via de Sinalização Wnt/genética
6.
AJNR Am J Neuroradiol ; 42(2): 228-232, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33303524

RESUMO

Optic nerve choristomas are rare entities in which a developmental focus of histologically normal tissue is abnormally located within or along a segment of the optic nerve. Although benign, choristomas may demonstrate slow growth, ultimately resulting in visual field deficits due to compression of the adjacent nerve in the few cases reported in the anterior fossa. Choristomas may have cystic components, though this has not been described in such lesions along the optic nerve. Here, a predominantly cystic optic nerve choristoma is described, with radiologic features mimicking those of an anterior cranial fossa neurenteric cyst. The case highlights the radiology-pathology correlates of choristomas and reviews the surgical approach and management of patients with such lesions.


Assuntos
Coristoma/diagnóstico , Coristoma/patologia , Defeitos do Tubo Neural/diagnóstico , Nervo Óptico/patologia , Glândulas Salivares , Coristoma/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade
7.
Rhinology ; 59(2): 173-180, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33129200

RESUMO

BACKGROUND: Neutrophils present as major inflammatory cells in refractory chronic rhinosinusitis with nasal polyps (CRSwNP), regardless of the endotype. However, their role in the pathophysiology of CRSwNP remains poorly understood. We investigated factors predicting the surgical outcomes of CRSwNP patients with focus on neutrophilic localization. METHODS: We employed machine-learning methods such as the decision tree and random forest models to predict the surgical outcomes of CRSwNP. Immunofluorescence analysis was conducted to detect human neutrophil elastase (HNE), Bcl-2, and Ki-67 in NP tissues. We counted the immunofluorescence-positive cells and divided them into three groups based on the infiltrated area, namely, epithelial, subepithelial, and perivascular groups. RESULTS: On machine learning, the decision tree algorithm demonstrated that the number of subepithelial HNE-positive cells, Lund-Mackay (LM) scores, and endotype (eosinophilic or non-eosinophilic) were the most important predictors of surgical outcomes in CRSwNP patients. Additionally, the random forest algorithm showed that, after ranking the mean decrease in the Gini index or the accuracy of each factor, the top three ranking factors associated with surgical outcomes were the LM score, age, and number of subepithelial HNE-positive cells. In terms of cellular proliferation, immunofluorescence analysis revealed that Ki-67/HNE-double positive and Bcl-2/HNE-double positive cells were significantly increased in the subepithelial area in refractory CRSwNP. CONCLUSION: Our machine-learning approach and immunofluorescence analysis demonstrated that subepithelial neutrophils in NP tissues had a high expression of Ki-67 and could serve as a cellular biomarker for predicting surgical outcomes in CRSwNP patients.


Assuntos
Pólipos Nasais , Rinite , Doença Crônica , Humanos , Pólipos Nasais/complicações , Pólipos Nasais/cirurgia , Infiltração de Neutrófilos , Neutrófilos , Rinite/complicações , Rinite/cirurgia , Resultado do Tratamento
8.
AJNR Am J Neuroradiol ; 41(10): 1786-1790, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32819895

RESUMO

Chordomas are rare primary bone malignancies derived from notochord remnants. The tumors often are slow-growing and often present with indolent, nonspecific symptoms. Nevertheless, chordomas are locally aggressive and highly prone to local recurrence, necessitating precise planning before biopsy and/or surgical resection. Familiarity with the imaging features of chordomas is, therefore, essential. This case highlights the typical imaging and pathologic features of a spinal chordoma as well as the surgical approach and the patient's subsequent outcome.


Assuntos
Cordoma/patologia , Neoplasias da Coluna Vertebral/patologia , Idoso , Dor nas Costas/etiologia , Cordoma/complicações , Cordoma/cirurgia , Humanos , Vértebras Lombares/patologia , Masculino , Recidiva Local de Neoplasia/patologia , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/cirurgia , Corpo Vertebral/patologia
9.
Biophys Chem ; 264: 106410, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32574923

RESUMO

Osmolytes are naturally occurring organic compounds that protect cellular proteins and other macromolecules against various forms of stress including temperature extremes. While biological studies have correlated the accumulation of certain classes of osmolytes with specific forms of stress, including thermal stress, it remains unclear whether or not these observations reflect an intrinsic chemical class hierarchy amongst the osmolytes with respect to effects on protein stability. In addition, very little is known in regards to the molecular elements of the osmolytes themselves that are essential for their functions. In this study, we use differential scanning fluorimetry to quantify the thermal stabilizing effects of members from each of the three main classes of protecting osmolytes on two model protein systems, C-reactive protein and tumor necrosis factor alpha. Our data reveals the absence of a strict chemical class hierarchy amongst the osmolytes with respect to protein thermal stabilization, and indicates differential responses of these proteins to certain osmolytes. In the second part of this investigation we dissected the molecular elements of amino acid osmolytes required for thermal stabilization of myoglobin and C-reactive protein. We show that the complete amino acid zwitterion is required for thermal stabilization of myoglobin, whereas removal of the osmolyte amino group does not diminish stabilizing effects on C-reactive protein. These disparate responses of proteins to osmolytes and other small molecules are consistent with previous observations that osmolyte effects on protein stability are protein-specific. Moreover, the data reported in this study support the view that osmolyte effects cannot be fully explained by considering only the solvent accessibility of the polypeptide backbone in the native and denatured states, and corroborate the need for more complex models that take into account the entire protein fabric.


Assuntos
Compostos Orgânicos/química , Proteínas/química , Aminoácidos/química , Proteína C-Reativa/química , Fluorometria/métodos , Humanos , Mioglobina/química , Concentração Osmolar , Desnaturação Proteica , Estabilidade Proteica , Temperatura , Fator de Necrose Tumoral alfa/química
10.
Sci Rep ; 10(1): 1350, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992801

RESUMO

Stacking fault energies (SFE) were determined in additively manufactured (AM) stainless steel (SS 316 L) and equiatomic CrCoNi medium-entropy alloys. AM specimens were fabricated via directed energy deposition and tensile loaded at room temperature. In situ neutron diffraction was performed to obtain a number of faulting-embedded diffraction peaks simultaneously from a set of (hkl) grains during deformation. The peak profiles diffracted from imperfect crystal structures were analyzed to correlate stacking fault probabilities and mean-square lattice strains to the SFE. The result shows that averaged SFEs are 32.8 mJ/m2 for the AM SS 316 L and 15.1 mJ/m2 for the AM CrCoNi alloys. Meanwhile, during deformation, the SFE varies from 46 to 21 mJ/m2 (AM SS 316 L) and 24 to 11 mJ/m2 (AM CrCoNi) from initial to stabilized stages, respectively. The transient SFEs are attributed to the deformation activity changes from dislocation slip to twinning as straining. The twinning deformation substructure and atomic stacking faults were confirmed by electron backscatter diffraction (EBSD) and transmission electron microscopy (TEM). The significant variance of the SFE suggests the critical twinning stress as 830 ± 25 MPa for the AM SS 316 L and 790 ± 40 MPa for AM CrCoNi, respectively.

11.
Dis Esophagus ; 33(5)2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31665266

RESUMO

Robots are increasingly used in minimally invasive surgery. We evaluated the clinical benefits of robot-assisted minimally invasive esophagectomy (RAMIE) in comparison with the conventional open esophageal surgery. From 2012 to 2016, 371 patients with esophageal squamous cell carcinoma underwent an Ivor Lewis or McKeown procedure at our institution. Of these, 130 patients underwent laparoscopic gastric conduit formation followed by RAMIE, whereas 241 patients underwent conventional esophageal surgery, including laparotomy and open esophagectomy (OE). We compared the short- and long-term clinical outcomes of these patients using the propensity score-based inverse probability of treatment weighting technique (IPTW). Among the early outcomes, the OE group showed a higher incidence of pneumonia (P = 0.035) and a higher requirement for vasopressors (P = 0.001). Regarding the long-term outcomes, all-cause mortality was significantly higher (P = 0.001) and disease-free survival was lower (P = 0.006) in the OE group. Wound-related problems also occurred more frequently in the OE group (P = 0.020) during the long-term follow-up. There was no statistical intergroup difference in the recurrence rates (P = 0.191). The Cox proportional-hazard analysis demonstrated that wound problems (HR 0.16, 95% CI 0.02-0.57; P = 0.017), pneumonia (HR 0.23, 95% CI 0.06-0.68; P = 0.019), and use of vasopressors (HR 0.14, 95% CI 0.08-0.25; P = 0.001) were independent predictors of mortality. RAMIE could be a better surgical option for selected patients with esophageal squamous cell carcinoma.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias de Cabeça e Pescoço , Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia/efeitos adversos , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Recidiva Local de Neoplasia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Resultado do Tratamento
12.
J Laryngol Otol ; 131(9): 801-804, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28693661

RESUMO

OBJECTIVE: Cultures obtained from pre-operative middle-ear swabs from patients with chronic otitis media have traditionally been used to guide antibiotic selection. This study investigated changes in the bacterial strains of the middle ear during chronic otitis media surgery. METHODS: Pre-operative bacterial cultures of otorrhoea, and peri-operative cultures of the granulation tissue in either the middle ear or mastoid cavity, were obtained. Post-operative cultures were selectively obtained when otorrhoea developed after surgery. RESULTS: Bacterial growth was observed in 45.5 per cent of pre-operative cultures, 13.5 per cent of peri-operative cultures and 4.5 per cent of post-operative cultures. Methicillin-resistant Staphylococcus aureus was identified as the most common bacteria in all pre-operative (32.4 per cent), peri-operative (52.4 per cent) and post-operative (71.4 per cent) tests, and the percentage of Methicillin-resistant S aureus increased from the pre- to the post-operative period. CONCLUSION: The bacterial culture results for post-operative otorrhoea showed low agreement with those for pre-operative or peri-operative culture, and strain re-identification was required.


Assuntos
Bactérias/classificação , Orelha Média/microbiologia , Processo Mastoide/microbiologia , Otite Média/cirurgia , Infecções Estafilocócicas/epidemiologia , Adolescente , Adulto , Idoso , Bactérias/isolamento & purificação , Criança , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Otite Média/microbiologia , Período Perioperatório , Adulto Jovem
13.
Eur J Vasc Endovasc Surg ; 53(2): 158-167, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27592735

RESUMO

OBJECTIVE: To evaluate treatment outcomes of in situ abdominal aortic reconstruction with cryopreserved arterial allograft (CAA) for patients with abdominal aortic infection. MATERIALS AND METHODS: A retrospective review of prospectively collected data was conducted of patients who underwent in situ aortic reconstruction using CAA for primary, secondary, or prosthetic infection of the abdominal aorta between May 2006 and July 2015, at a single institution. Clinical presentation, indications for treatment, procedural details, early post-operative mortality and morbidity, late death, and graft related complications during the follow up period were investigated. Patient survival and event free survival (any death or re-operation) were calculated using the Kaplan-Meier method. RESULTS: Twenty-five patients (male, n = 20, 80%; mean age, 70.2 ± 8.7 years) underwent in situ abdominal aortic reconstruction (48% aortic, 52% aorto-bi-iliac) with vessel size and ABO matched CAA for treatment of abdominal aortic infection caused by infected abdominal aortic aneurysm (n = 15), aortic prosthesis infection (n = 7), aortic reconstruction with concomitant colon resection (n = 2), and primary suppurative aortitis (n = 1). The median follow up was 19.1 months (range 1-73 months). There were seven post-operative deaths including two (8%) early (<30 days) and five (20%) late deaths There were three (12%) graft related complications including thrombotic occlusion of the CAA, aneurysmal dilatation, and aorto-enteric fistula. Three years after CAA implantation, patient survival was 74% and the event free survival was 58%. CONCLUSIONS: It is believed that in situ abdominal aortic reconstruction with CAA is a useful option for treating primary, secondary, or prosthetic infection of the abdominal aorta.


Assuntos
Aorta Abdominal/cirurgia , Bioprótese , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Criopreservação , Infecções Relacionadas à Prótese/cirurgia , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/microbiologia , Aortografia/métodos , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Angiografia por Tomografia Computadorizada , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Desenho de Prótese , Infecções Relacionadas à Prótese/diagnóstico por imagem , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/mortalidade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
14.
J Laryngol Otol ; 129(2): 168-73, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25695279

RESUMO

BACKGROUND: Genetic alteration of cyclin-dependent kinase inhibitors has been associated with carcinogenesis mechanisms in various organs. OBJECTIVE: This study aimed to evaluate the expression and mutational analysis of Cip/Kip family cyclin-dependent kinase inhibitors (p21CIP1/WAF1, p27KIP1 and p57KIP2) in early glottic cancer. METHODS: Expressions of Cip/Kip family and p53 were determined by quantitative reverse transcription polymerase chain reaction and densitometry. For the analysis of p21 inactivation, sequence alteration was assessed using single-strand conformational polymorphism polymerase chain reaction. Additionally, the inactivation mechanism of p27 and p57 were investigated using DNA methylation analysis. RESULTS: Reduced expression of p27 and p57 were detected in all samples, whereas the expression of p21 was incompletely down-regulated in 6 of 11 samples. Additionally, single-strand conformational polymorphism polymerase chain reaction analysis showed the p53 mutation at exon 6. Methylation of p27 and p57 was detected by DNA methylation assay. CONCLUSION: Our results suggest that the Cip/Kip family may have a role as a molecular mechanism of carcinogenesis in early glottic cancer.


Assuntos
Carcinoma de Células Escamosas/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p27/genética , Inibidor de Quinase Dependente de Ciclina p57/genética , Glote/patologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias Laríngeas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Inibidor de Quinase Dependente de Ciclina p27/biossíntese , Inibidor de Quinase Dependente de Ciclina p57/biossíntese , Análise Mutacional de DNA/métodos , Glote/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Polimorfismo Conformacional de Fita Simples , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço
15.
J Periodontal Res ; 50(5): 602-13, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25393899

RESUMO

BACKGROUND AND OBJECTIVE: Resistin was recently reported to play a role in inflammation-related diseases such as arthritis. However, the precise role of resistin in chronic inflammatory diseases, such as periodontal disease, remains unclear. The aim of this study was to investigate the combined effects of nicotine and lipopolysaccharide (LPS) on the expression of resistin and to assess whether resistin expression influences the levels of inflammatory cytokines, extracellular matrix (ECM) molecules and MMPs in human periodontal ligament cells (PDLCs) stimulated with both nicotine and LPS. MATERIAL AND METHODS: PDLCs were pretreated with isoproterenol or resistin-specific small interfering RNA (siRNA), stimulated with LPS plus nicotine for 24 h, and then monitored for the production of inflammatory mediators. The concentrations of prostaglandin E2 (PGE2) and nitric oxide (NO) were measured by radioimmunoassay and the Griess method, respectively. RT-PCR and western blot analysis were used to measure the levels of mRNA and protein, respectively. Western blot analysis was also used to assess the activation of various signal-transduction pathways. RESULTS: Treatment with nicotine plus LPS up-regulated the expression of resistin mRNA and the production of resistin protein in PDLCs in a time- and concentration-dependent manner. Isoproterenol-mediated interference with the function of resistin, or siRNA-mediated knockdown of resistin expression, markedly attenuated the LPS plus nicotine-mediated stimulation of PGE2 and NO production, the production of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase proteins and the expression of proinflammatory cytokines [tumor necrosis factor-α, interleukin (IL)-1ß, IL-6 and IL-12] and MMPs (MMP-1, MMP-2 and MMP-9); however, these treatments restored the expression of ECM molecules. Furthermore, pretreatment with isoproterenol or resistin-specific siRNA blocked nicotine plus LPS-induced activation of phosphoinositide-3-kinase, glycogen synthase kinase-3 beta, ß-catenin, p38, ERK, JNK and nuclear factor-κB. CONCLUSION: This is the first study to show that the inhibition of resistin, by either a pharmacological or a genetic silencing approach, has anti-inflammatory effects. These effects include decreased levels of inflammatory cytokines and the prevention of ECM breakdown in a nicotine plus LPS-stimulated PDLC model.


Assuntos
Ligamento Periodontal , Ciclo-Oxigenase 2 , Humanos , Lipopolissacarídeos , Nicotina , Resistina
16.
Int J Clin Pract ; 69(4): 444-53, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25363606

RESUMO

AIM: To explore the rate of add-on therapy with solifenacin in men with voiding and storage lower urinary tract symptoms (LUTS) after tamsulosin monotherapy and to explore predictive factors for starting solifenacin add-on therapy. METHODS: Men aged ≥ 45 years with IPSS ≥ 12 and symptoms of OAB (OAB-V8 ≥ 8, micturition ≥ 8/24 h, urgency ≥ 2/24 h) were enrolled to receive tamsulosin 0.2 mg once daily. After 4 weeks, men with residual symptoms of OAB and reported 'dissatisfied' or 'a little satisfied' were received solifenacin 5 mg in combination with tamsulosin monotherapy. Subjects completed an IPSS, a Quality of life (QoL) index, OAB V8, and an International Consultation of Incontinence Questionnaire (ICIQ)-Male LUTS, and patient perception of bladder condition (PPBC) at baseline and week 4. RESULTS: Of a total of 305 patients, 254 patients completed 4 weeks of tamsulosin treatment. For 176 patients, solifenacin was added (69.3%). Significant predictive factors of solifenacin add-on therapy included long LUTS duration, high IPSS, number of micturitions per 24 h, more urgency episodes, high urgency severity score in a voiding diary and high OAB V8 score. Based on multivariable analysis, potential predictive factors of solifenacin add-on therapy included long LUTS duration (OR = 1.008, 95% CI: 1.001-1.014), high serum PSA (OR = 1.543, 95% CI: 1.136-2.095) and small prostate size (OR = 0.970, 95% CI: 0.947-0.994) (p < 0.05). IPSS, daytime micturitions and urgency episodes, OAB V8 scores, ICIQ and PPBC were improved after tamsulosin monotherapy. CONCLUSIONS: Two thirds of men with voiding and storage LUTS needed to add anticholinergics after 4 weeks of tamsulosin monotherapy. Patients with longer lasting symptoms and storage symptoms with small prostate volume may require the anticholinergic add-on.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Antagonistas Muscarínicos/uso terapêutico , Succinato de Solifenacina/uso terapêutico , Sulfonamidas/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Agentes Urológicos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Tansulosina
17.
Int J Clin Pract ; 68(12): 1496-502, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25284747

RESUMO

AIMS: In spite of the reported efficacy and safety of antimuscarinics in men with OAB (overactive bladder) and BPO (benign prostatic obstruction), many patients do not persist with the treatment. We aimed to evaluate persistence and the reasons for the discontinuation of solifenacin add-on therapy in men with residual symptoms of OAB after tamsulosin monotherapy for BPO in a real clinical environment. METHODS: Men aged ≥ 45 years with IPSS ≥ 12 and symptoms of OAB (OAB-V8 ≥ 8, micturition ≥ 8/24 h, urgency ≥ 2/24 h) were prescribed tamsulosin 0.2 mg. After 4 weeks, men who had residual symptoms of OAB (OAB-V8 ≥ 8, micturition ≥ 8/24 h, urgency ≥ 1/24 h) and reported that they were 'dissatisfied' or 'a little satisfied' with the therapy were enrolled and prescribed solifenacin 5 mg in combination with tamsulosin. After 52 weeks, persistence and the reasons for the discontinuation of solifenacin were evaluated. Factors related to persistence were analysed. RESULTS: Of the 305 men who had been treated with tamsulosin, 176 were prescribed solifenacin. After 52 weeks, 44 (25%) remained on solifenacin therapy. Of the 132 who discontinued solifenacin, 85 were evaluated on the reason for discontinuation. The three most common reasons for discontinuation were adverse events (AEs) (35%), lack of efficacy (33%), and improvement in symptoms (16%). The aggravation of voiding symptoms was the most common AE leading to discontinuation. Retention was observed in 11 men. None of the demographical or clinical characteristics were significantly related to persistence. CONCLUSIONS: Only 25% men with OAB and BPO remained on antimuscarinic add-on therapy after 1 year, mostly because of AEs and lack of efficacy. Realistic data should be added to what is already known about antimuscarinic treatment in men by including patients who were excluded or who dropped out of well-designed clinical trials.


Assuntos
Quimioterapia Combinada , Antagonistas Muscarínicos/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Bexiga Urinária Hiperativa/tratamento farmacológico , Humanos , Masculino , Antagonistas Muscarínicos/efeitos adversos , Quinuclidinas/administração & dosagem , Succinato de Solifenacina/farmacologia , Succinato de Solifenacina/uso terapêutico , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Tansulosina , Tetra-Hidroisoquinolinas/administração & dosagem
18.
Int J Tuberc Lung Dis ; 18(8): 995-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25199019

RESUMO

An association has been suggested between Marfan syndrome (MFS) and the nodular bronchiectatic form of lung disease caused by non-tuberculous mycobacteria (NTM). We evaluated the prevalence of bronchiectasis in 79 adult patients with MFS using computed tomography (CT) imaging. Airway dilation indicative of bronchiectasis (22/79, 28%) and bronchioloectasis (10/79, 13%) were relatively common, although the extent of dilation was not severe and was frequently confined to a single lobe. However, bronchiolitis was evident in only three patients (4%), and no patient was diagnosed with NTM lung disease.


Assuntos
Bronquiectasia/epidemiologia , Síndrome de Marfan/complicações , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Micobactérias não Tuberculosas/isolamento & purificação , Adulto , Bronquiectasia/microbiologia , Bronquiolite/epidemiologia , Bronquiolite/microbiologia , Feminino , Humanos , Masculino , Síndrome de Marfan/microbiologia , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/microbiologia , Prevalência , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
19.
Allergy ; 69(4): 517-26, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24611950

RESUMO

BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory process in the nasal cavity and paranasal sinuses, and bacteria have been considered to be a cause. Indeed, recent evidence indicates that bacteria-derived extracellular vesicles (EV) appear to be an important causative agent of inflammatory diseases. Here, we aimed to evaluate the diversity of nasal microbiota and their secreted EV in patients with CRS. METHODS: Nasal lavage (NAL) fluid samples were obtained from five patients with CRS with polyposis, three patients with CRS without polyposis, and three non-CRS controls. After preparation of bacteria and EV from samples using differential centrifugation, genomic DNA was extracted and 16S-rDNA amplicons were subjected to high-throughput pyrosequencing on a Roche 454 GS-FLX platform. RESULTS: Metagenomics showed that bacteria composition was positively correlated with EV composition. Samples from patients with CRS had greater bacterial abundance and lower diversity, both from bacteria and the EV portion of samples, compared with non-CRS samples. At each phylogenetic level, Bacteroidetes decreased while Proteobacteria increased in the CRS group at the phylum level. At the genus level, Prevotella spp. decreased in the CRS group, while Staphylococcus spp. increased from both bacteria and EV. Moreover, Staphylococcus aureus and its secreting EV compositions were higher in samples from CRS with polyps compared with CRS without polyps. CONCLUSIONS: These results suggest that patients with CRS have altered nasal microbiota and decreased diversity in bacterial compositions as well as increased S. aureus abundance in those patients with polyps.


Assuntos
Microbiota , Mucosa Nasal/microbiologia , Rinite/microbiologia , Sinusite/microbiologia , Adulto , Idoso , Bactérias/classificação , Bactérias/genética , Biodiversidade , Exossomos , Feminino , Humanos , Masculino , Metagenoma , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Filogenia , RNA Ribossômico 16S , Rinite/patologia , Sinusite/patologia , Adulto Jovem
20.
Int J Tuberc Lung Dis ; 18(3): 363-70, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24670577

RESUMO

BACKGROUND: The association of inhaler use with haemoptysis has rarely been reported in patients with non-cystic fibrosis (CF) bronchiectasis. OBJECTIVE: To elucidate the effect of inhaler use on the development of haemoptysis in patients with non-CF bronchiectasis. METHODS: In a case-crossover study of 192 non-CF bronchiectasis patients with a history of haemoptysis and inhaler use, the risk of haemoptysis associated with the use of inhalers was elucidated. Two inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA), one long-acting muscarinic antagonist and one short-acting ß2-agonist (SABA) were evaluated. The case and control periods were defined respectively as 030 and 180210 days before haemoptysis. RESULTS: The risk of haemoptysis during the case period was 3.51 times higher than during the control period with any use of inhalers (95%CI 1.966.28). The results of clinically significant haemoptysis showed good agreement with those of total events. These associations were consistent with the sensitivity analyses. In the sub-analysis according to inhaler type, ICS/LABA and SABA were significantly associated with an increased risk of haemoptysis (aOR 2.62, 95%CI 1.255.45; aOR 2.51, 95%CI 2.235.15). CONCLUSIONS: In patients with non-CF bronchiectasis, the use of inhalers, especially including 2-agonist, was associated with an increased risk of haemoptysis.


Assuntos
Corticosteroides/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Bronquiectasia/tratamento farmacológico , Hemoptise/etiologia , Antagonistas Muscarínicos/efeitos adversos , Nebulizadores e Vaporizadores , Administração por Inalação , Corticosteroides/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Idoso , Bronquiectasia/diagnóstico , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/administração & dosagem , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
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