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1.
Childs Nerv Syst ; 40(3): 919-924, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37930424

RESUMO

A 13-year-old female patient presented with painless vision loss and proptosis for 18 months. Imaging findings were highly suggestive of a supraorbital aneurysmal bone cyst (ABC) for which she underwent complete surgical excision. Postoperatively, she developed left hemiparesis. Computed tomography angiography (CTA) revealed right complete internal carotid arterial (ICA) thrombosis. This was managed conservatively, and she improved in hemiparesis over the next 3 weeks. Histopathology report revealed osteosarcoma with secondary ABC, for which she was referred for radiotherapy. At 1.5 months follow-up, the patient's left lower limb power improved to 4 + /5. She was walking without support, and her left upper limb power was 4/5.


Assuntos
Cistos Ósseos Aneurismáticos , Neoplasias Ósseas , Osteossarcoma , Adolescente , Feminino , Humanos , Cistos Ósseos Aneurismáticos/complicações , Cistos Ósseos Aneurismáticos/diagnóstico por imagem , Cistos Ósseos Aneurismáticos/cirurgia , Neoplasias Ósseas/complicações , Angiografia por Tomografia Computadorizada , Paresia
2.
BMC Biol ; 21(1): 79, 2023 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-37041515

RESUMO

BACKGROUND: Baleen whales are a clade of gigantic and highly specialized marine mammals. Their genomes have been used to investigate their complex evolutionary history and to decipher the molecular mechanisms that allowed them to reach these dimensions. However, many unanswered questions remain, especially about the early radiation of rorquals and how cancer resistance interplays with their huge number of cells. The pygmy right whale is the smallest and most elusive among the baleen whales. It reaches only a fraction of the body length compared to its relatives and it is the only living member of an otherwise extinct family. This placement makes the pygmy right whale genome an interesting target to update the complex phylogenetic past of baleen whales, because it splits up an otherwise long branch that leads to the radiation of rorquals. Apart from that, genomic data of this species might help to investigate cancer resistance in large whales, since these mechanisms are not as important for the pygmy right whale as in other giant rorquals and right whales. RESULTS: Here, we present a first de novo genome of the species and test its potential in phylogenomics and cancer research. To do so, we constructed a multi-species coalescent tree from fragments of a whole-genome alignment and quantified the amount of introgression in the early evolution of rorquals. Furthermore, a genome-wide comparison of selection rates between large and small-bodied baleen whales revealed a small set of conserved candidate genes with potential connections to cancer resistance. CONCLUSIONS: Our results suggest that the evolution of rorquals is best described as a hard polytomy with a rapid radiation and high levels of introgression. The lack of shared positive selected genes between different large-bodied whale species supports a previously proposed convergent evolution of gigantism and hence cancer resistance in baleen whales.


Assuntos
Neoplasias , Baleias , Animais , Filogenia , Genoma , Genômica , Neoplasias/genética
3.
BMC Biol ; 21(1): 229, 2023 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-37867198

RESUMO

BACKGROUND: Venoms, which have evolved numerous times in animals, are ideal models of convergent trait evolution. However, detailed genomic studies of toxin-encoding genes exist for only a few animal groups. The hyper-diverse hymenopteran insects are the most speciose venomous clade, but investigation of the origin of their venom genes has been largely neglected. RESULTS: Utilizing a combination of genomic and proteo-transcriptomic data, we investigated the origin of 11 toxin genes in 29 published and 3 new hymenopteran genomes and compiled an up-to-date list of prevalent bee venom proteins. Observed patterns indicate that bee venom genes predominantly originate through single gene co-option with gene duplication contributing to subsequent diversification. CONCLUSIONS: Most Hymenoptera venom genes are shared by all members of the clade and only melittin and the new venom protein family anthophilin1 appear unique to the bee lineage. Most venom proteins thus predate the mega-radiation of hymenopterans and the evolution of the aculeate stinger.


Assuntos
Venenos de Abelha , Abelhas/genética , Animais , Perfilação da Expressão Gênica , Transcriptoma , Genômica , Duplicação Gênica
4.
J Craniofac Surg ; 33(8): e848-e853, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35946819

RESUMO

PURPOSE: To evaluate the quantitative (cephalometric) aspects of the craniofacial deformities in transfusion-dependent beta-thalassemia (TDT) patients. MATERIALS AND METHODS: Sixty-five TDT patients receiving a regular blood transfusion in the Department of Pediatrics of age group 5 to 8 years (younger) and 15 years and above (older) were compared with control groups of similar age using cephalograms (lateral and posterior-anterior view). RESULTS AND OBSERVATION: The prevalence of skeletal class II tendency is higher in thalassemic patients that do not improve with age. The thalassemic patients were found to show large angle ANB i.e. Angle between points point a, nasion and point B (ANB), large flexure angle, small angle SNB i.e. Angle between points sella, nasion and point B (SNB), and normal angle SNA i.e. Angle between points sella, nasion and point A (SNA) angles suggestive of retrognathic mandible. The thalassemic patients were observed to have smaller transverse widths and thickened calvarium on the posterior-anterior view. CONCLUSION: The skeletal class II malocclusion appears to be a manifestation of generalized growth retardation/delayed puberty in thalassemic patients leading to diminished mandibular growth, rather than maxillary prognathism due to marrow hyperplasia.


Assuntos
Anormalidades Craniofaciais , Má Oclusão Classe II de Angle , Talassemia beta , Humanos , Criança , Pré-Escolar , Talassemia beta/complicações , Talassemia beta/terapia , Cefalometria , Mandíbula , Maxila
5.
Phys Occup Ther Pediatr ; 41(6): 637-654, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33745416

RESUMO

AIMS: Describe the pre-operative and post-operative stages of physical therapy examination, rehabilitation interventions and outcomes in craniopagus conjoined twins (CCT). METHODS: 27-months old total vertical types III CCT were admitted for surgical treatment. A structured rehabilitation program (functional mobility, balance training, sensory stimulation, communication, orthotic management, and caregiver education) was delivered post-operatively at different stages of surgery. The total duration of post-separation rehabilitation was 15 months for Twin A and 23 months for Twin B. RESULTS: Pre-operative WeeFIM was 67/126 for both the twins. Post-separation, Twin A improved to a state of complete independence in walking, step climbing, and hand function with a discharge WeeFIM score of 84/126. However, Twin B was completely dependent in bed mobility and transfer activities during discharge (WeeFIM-18/126). Minimal change in functional status was noted in Twin B (discharge FSS score-19/30). Both the twins were transferred to a regional hospital for long-term care. At 67 months of age, Twin B lost his life due to chest infection. CONCLUSIONS: Vestibular based therapies, balance, and postural control may be prioritized in the rehabilitation process of CCT. Greater communication and coordination among physical, occupational therapists and other rehabilitation professionals are recommended for successful outcome in these unique cases.


Assuntos
Procedimentos de Cirurgia Plástica , Gêmeos Unidos , Pré-Escolar , Humanos , Modalidades de Fisioterapia , Gêmeos Unidos/cirurgia
6.
Soft Matter ; 16(17): 4162-4172, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32319974

RESUMO

High performance thermoresponsive soft, controllable and reversible actuators are highly desirable for diverse applications. The practical implementation of the existing poly(N-isopropylacrylamide) (pNipam) based soft thermoresponsive actuators faces serious limitations due to their functional requirement of proximal bulk solvent medium. In this work, addressing this issue, we report the development of a bilayer based actuator composed of a solvent responsive biodegradable polymer and temperature responsive pNipam. The designed bilayer is capable of achieving reversible and irreversible actuation as needed when exposed to a physiological range of body temperature, without any solvent bath around. The solvent or water supplied by the pNipam layer at its lower critical solution temperature (LCST) builds a concentration gradient across the thickness of the polymer layer. The concentration gradient results in a strain gradient, causing an out-of-plane folding of the bilayer. The underlying coupled diffusion-deformation interaction during folding and unfolding is incorporated in the reported finite element model, capable of predicting actuation characteristics under different initial conditions. The combined experimental and modelling effort in this work highlights the possibility of engineering 2-dimensional films into complex 3-dimensional shapes, which could have potential applications in soft machines and robotics.

7.
Int J Cancer ; 142(4): 805-812, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28994107

RESUMO

Glioblastoma (GBM) is characterized by the presence of hypoxia, stemness and local invasiveness. We have earlier demonstrated that FAT1 promotes invasiveness, inflammation and upregulates HIF-1α expression and its signaling in hypoxic GBM. Here, we have identified the role of FAT1 in regulating EMT (epithelial-mesenchymal transition) and stemness characteristics in GBM. The expression of FAT1, EMT (Snail/LOX/Vimentin/N-cad), stemness (SOX2/OCT4/Nestin/REST) and hypoxia markers (HIF-1α/VEGF/PGK1/CA9) was upregulated in ≥39% of GBM tumors (n = 31) with significant positive correlation (p ≤ 0.05) of the expression of FAT1 with LOX/Vimentin/SOX2/HIF-1α/PGK1/VEGF/CA9. Furthermore, positive correlation (p ≤ 0.01) of FAT1 with Vimentin/N-cad/SOX2/REST/HIF-1α has been observed in TCGA GBM-dataset (n = 430). Analysis of cells (U87MG/A172) exposed to severe hypoxia (0.2%O2 ) revealed elevated mRNA expression of FAT1, EMT (Snail/LOX/Vimentin/N-cad), stemness (SOX2/OCT4/Nestin/REST) and hypoxia markers (HIF-1α/PGK1/VEGF/CA9) as compared to their normoxic (20%O2 ) counterparts. FAT1 knockdown in U87MG/A172 maintained in severe hypoxia and in normoxic primary glioma cultures led to significant reduction of EMT/stemness markers as compared to controls. HIF-1α knockdown in U87MG cells markedly reduced the expression of all the EMT/stemness markers studied except for Nestin and SOX2 which were more under the influence of FAT1. This indicates FAT1 has a novel regulatory effect on EMT/stemness markers both via or independent of HIF-1α. The functional relevance of our study was corroborated by significant reduction in the number of soft-agar colonies formed in hypoxic-siFAT1 treated U87MG cells. Hence, our study for the first time reveals FAT1 as a novel regulator of EMT/stemness in hypoxic GBM and suggests FAT1 as a potential therapeutic candidate.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Caderinas/genética , Glioblastoma/genética , Glioblastoma/patologia , Células-Tronco Neoplásicas/patologia , Neoplasias Encefálicas/metabolismo , Caderinas/biossíntese , Caderinas/metabolismo , Hipóxia Celular/genética , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Glioblastoma/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Células-Tronco Neoplásicas/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Células Tumorais Cultivadas
8.
J Gastroenterol Hepatol ; 32(1): 237-243, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27218672

RESUMO

BACKGROUND AND AIM: Percutaneous radiologic interventions are increasingly being used in management of Budd-Chiari syndrome (BCS). Minimal invasive approach has resulted in excellent long-term outcomes. We evaluated the treatment efficacy and safety of radiological intervention in patients with BCS. METHODS: Between January 2008 and June 2014, 190 patients with BCS underwent endovascular procedures (hepatic vein, collateral vein or inferior vena cava [IVC] plasty with or without stenting, or transjugular intrahepatic portosystemic shunting [TIPSS]). Clinical features, biochemical profile, and stent patency were monitored pre-procedure and post-procedure, and for a median duration of 42 (12-88) months. RESULTS: Of 190 patients (mean [SD] age = 26.9 [11.5] years; 102 men), imaging revealed hepatic vein obstruction in 147 patients, IVC obstruction in 40 patients, and concomitant hepatic vein and IVC obstruction in three patients. At presentation, the radiological interventions included hepatic vein plasty/stenting in 38 patients, collateral vein stenting in three patients, IVC plasty/stenting in 40 patients, both IVC and hepatic vein stenting in three patients, and TIPSS in 106 patients. Response was seen in 153 patients (80.5%). Repeat interventions were required in 19 patients (10.0%). Complications were noted in nine patients (4.7%). CONCLUSION: Our study demonstrates that venous recanalization and TIPSS for BCS are safe and efficacious.


Assuntos
Síndrome de Budd-Chiari/cirurgia , Procedimentos Endovasculares/métodos , Adulto , Síndrome de Budd-Chiari/diagnóstico por imagem , Constrição Patológica , Feminino , Veias Hepáticas/diagnóstico por imagem , Veias Hepáticas/patologia , Humanos , Masculino , Derivação Portossistêmica Transjugular Intra-Hepática , Stents , Resultado do Tratamento , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/patologia , Adulto Jovem
9.
Neurol India ; 64(1): 62-5, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26754994

RESUMO

INTRODUCTION: Patients with traumatic brain injury (TBI) need frequent computed tomography (CT) of the head for assessment and management. In view of the associated polytrauma, hemodynamic instability, and various in-dwelling catheters and tubes, shifting of patients for CT scans may be difficult. AIMS AND OBJECTIVES: To assess the role of mobile CT (Ceretom®; NeuroLogica Corporation, Boston, MA, USA) in a trauma center with respect to patient management. MATERIALS AND METHODS: In this retrospective study over 67 months (June 2009 to January 2015), the number of CT scans done, the time taken for CT and downtime were evaluated. Also, for the first 1000 mobile CT scans, the clinical and radiological records of all patients with TBI who underwent imaging using the mobile CT scanner in the intensive care units (ICUs) were analyzed. OBSERVATIONS AND RESULTS: A total of 10,000 mobile CT scans were done on the mobile CT scanner till January 5, 2015. Of the first 1000 patients evaluated, 75.3% had severe TBI, 15.1% had moderate TBI, and 9.6% had mild TBI. 78.1% patients were on ventilator, with 80.2% requiring sedation and 8.4%, an inotropic support. An in situ intracranial pressure monitoring was present in 21.1% of patients. In all, 12.4% of patients had long-bone fractures requiring skeletal traction; and, the tube thoracostomy was in-situ in 7.4%. No adverse events related to line malfunction/pullout occurred. The mean time for the performance of imaging using the mobile CT scan was 11.6 minutes compared with 47.8 minutes when patients were shifted to a conventional CT scan suite. The machine was nonfunctional 94 times, with an average downtime of 4.2 hours (range 2-72 hours). The life-cycle cost per mobile CT scan was Rs. 1340. CONCLUSIONS: A mobile CT has considerably changed the management response time in the neurosurgical intensive care unit (ICU) setup and decreased patient transfer times and the associated complications. Inclusion of a mobile CT scanner in the armamentarium of a neurosurgeon as a "bedside tool" can dramatically change decision making and the response time. It should be considered as the standard of care in any large-volume emergency department or neurosurgical facility.


Assuntos
Lesões Encefálicas Traumáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Humanos , Índia , Estudos Retrospectivos , Centros de Traumatologia
10.
Childs Nerv Syst ; 31(2): 269-77, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25227164

RESUMO

PURPOSE: Growing skull fractures are rare complications of traumatic skull fractures in children. The authors aim to share their experience in management of such lesions and analyse clinicoradiological features, surgical management and outcome in addition to prognostication factors. MATERIALS AND METHODS: Retrospective study performed to include patients ≤18 years operated for growing skull fractures at our trauma centre from December 2007 to February 2014. RESULTS: Forty-three children were operated. Mean age at presentation was 4.57 years (range 7 months-18 years). Mean duration of onset of symptoms from initial trauma was 3.34 months (2 days-24 months). Mean interval from symptom onset to surgical repair was 11.6 months (1 week-15 years). Progressive non-tender scalp swelling was the most common symptom and parietal, the most common location. Duraplasty alone was performed in four patients while combined duro-cranioplasty was performed in the rest. Mean follow-up duration was 31 months (4-72 months). Subdural hygroma was associated in six cases. Two patients expired; rest all survivors had good-to-excellent cosmetic outcomes. CONCLUSIONS: Being the second largest series to date, it adds significant valuable contribution to this topic. Poor prognostic factors were age >8 years, females, large defects (>7 cm), severe head injury at initial trauma, defects crossing midline and delayed repair (>8 months). Delayed onset seizures and new onset/progression of pre-existing deficits can be indirect markers of evolution. Surgical repair with water-tight dural closure is the standard treatment. Emphasis on early treatment is highlighted which is probably beneficial in improving neurological deficits. Good-to-excellent outcomes are noted in majority, even in cases with delayed presentations.


Assuntos
Fraturas Cranianas/patologia , Fraturas Cranianas/cirurgia , Adolescente , Criança , Pré-Escolar , Traumatismos Craniocerebrais/complicações , Progressão da Doença , Dura-Máter/cirurgia , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Crânio/cirurgia
11.
Brain Inj ; 29(13-14): 1717-24, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26399723

RESUMO

INTRODUCTION: Literature remains sparse regarding decompressive craniectomy (DC) in traumatic brain injury (TBI) in very young children. This study analysed the indications, complications and outcome of young children undergoing DC for TBI at our institute. STUDY DESIGN: Retrospective. OBSERVATIONS: The total number of patients was 71. Mean age was 1.6 years. Mean duration from injury to surgery was 11.9 hours (range = 3-80 hours). Around 50% had severe head injury. Intracranial pressure (ICP) monitoring was done in 33 patients. Mean ICP was 22.2 mm Hg (range = 9-50 mm Hg). The threshold ICP for surgery was 15 mm Hg. Perioperative mortality was 50% each for severe TBI (18/36) and diffuse cerebral edema (7/14), and 58% for infants (4/7). Ninety per cent of expired patients had ICP > 20 mm Hg. Mean follow-up duration was 19.6 months (range = 2-42 months). Except one, all survivors had good-to-excellent outcomes (Glasgow outcome scale extended; GOS-E = 7-8). CONCLUSIONS: Decompressive craniectomy offers a survival advantage in almost 50% of young children with severe TBI and should be used judiciously. The highest mortality was within the 1st week of surgery. The cut-off limit of 20 mm Hg for surgical decompression might not be applicable to young children and a low threshold ICP needs to be considered. Factors associated with increased mortality are high opening ICP (>20 mm Hg), GCS <8, diffuse cerebral oedema and infant age group. Timing of DC remains crucial. Further prospective studies are necessary to optimize the timing and ICP limit for surgical decompression.


Assuntos
Lesões Encefálicas/cirurgia , Craniectomia Descompressiva/métodos , Fatores Etários , Edema Encefálico/etiologia , Lesões Encefálicas/fisiopatologia , Pré-Escolar , Feminino , Humanos , Índia , Lactente , Recém-Nascido , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/cirurgia , Pressão Intracraniana/fisiologia , Masculino , Estudos Retrospectivos , Centros de Traumatologia , Resultado do Tratamento
12.
Pediatr Neurosurg ; 50(5): 250-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26287640

RESUMO

INTRODUCTION: Traumatic posterior fossa extradural hematomas (PFEDH) are rare lesions constituting <10% of all extradural hematomas. Reliance on clinical findings alone is not recommended as these are nonspecific; for all suspicious cases, it is advisable to conduct a CT scan. Only a handful of pediatric studies have been reported analyzing the outcome of such lesions. The aim of our study was to analyze outcomes for children with PFEDH managed at our apex trauma center. MATERIALS AND METHODS: We conducted a retrospective analysis of pediatric patients (≤18 years) admitted with a diagnosis of traumatic PFEDH from January 2008 to February 2014. RESULTS: Of 22 patients, 16 were managed surgically (group 1) and 6 conservatively (group 2); 1 failed conservative treatment (due to an increased EDH volume). Mean age was 11.7 years (range 2-18 years). Falls were the most common cause of injury. Vomiting and loss of consciousness were the most frequent presenting features. There were 18 mild, 2 moderate and 2 severe head injuries. The mean volume of EDH was 37.1 ml (range 18-100 ml) and 10.3 ml (8-16 ml) in the operative and conservative subgroups, respectively. Occipital bone fracture was seen in 16 cases with supratentorial extension in 11. Four complications were noted in 3 cases. Mean follow-up duration was 25.1 months (range 3-34 months). Except for 1 patient, all had excellent outcomes. There was no mortality. CONCLUSIONS: Traumatic pediatric PFEDHs are rare. Both the clinical status of the patient and the volume of the hematoma need to be assessed before deciding on surgery. Most cases have associated occipital bone fractures and around half have supratentorial extension; these need to be carefully assessed preoperatively. Torrential venous bleeding can be a major problem due to rupture of the adjacent sinuses. Timely intervention is crucial for achieving good outcome, keeping in view a low threshold for surgical evacuation. Although not innovative, this second-largest case series provides additional data and contributes to the existing literature on such lesions in pediatric patients.


Assuntos
Hematoma Epidural Craniano/diagnóstico por imagem , Hematoma Epidural Craniano/terapia , Procedimentos Neurocirúrgicos/métodos , Adolescente , Criança , Pré-Escolar , Fossa Craniana Posterior , Feminino , Seguimentos , Hematoma Epidural Craniano/complicações , Hematoma Epidural Craniano/cirurgia , Humanos , Índia , Masculino , Radiografia , Índice de Gravidade de Doença , Centros de Atenção Terciária , Centros de Traumatologia , Resultado do Tratamento
13.
Neurol India ; 63(1): 40-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25751468

RESUMO

INTRODUCTION: Odontoid fractures constitute 9-20% of all adult cervical spine fractures. The present study was carried out to focus on the nuances involved in the surgical management of odontoid fractures. MATERIALS AND METHODS: Patients with an odontoid fracture, admitted for surgical stabilization, between January 2008 and March 2014, were included in the study. RESULTS: Among 142 patients [127 male and 15 female patients; median age: 28 years range 4-75 years], type II odontoid fractures were present in 111, type IIA fractures in 8, and type III fractures in 23 patients. 58.5% patients had been involved in a motor vehicular accident while 38.7% had sustained a fall. Eighty-five patients (59.9%) with a well-reduced fracture and an intact transverse ligament underwent anterior odontoid screw (OS) placement; the other 57 patients (40.1%) underwent posterior fixation (PF). The mean follow-up duration was 22 months (range: 6 months-5.4 years). OS placement was successful in 82 patients (96.5%) with a fusion rate of 95% (95.8% in type II, 100% in type III, and 75% in type IIA odontoid fractures). The procedure-related morbidity was 11.7%. One patient died of sub-arachnoid hemorrhage (SAH) that occurred during OS placement. The PF procedures had a better fusion rate (96.5%). The latter patients, however, had significant restriction of their neck movements and an overall morbidity of 8.7%. The revision surgery rates after OS placement and PF fixation were 7% and 3.5%, respectively. CONCLUSIONS: Anterior OS fixation shows excellent fusion rates and should be the first-line management in reduced/non-displaced acute type II (including type IIA) and high type III odontoid fractures as it preserves cervical motion. PF, that has also been associated with an excellent fusion rate, should be reserved for patients where OS fixation has either failed or has not been feasible.


Assuntos
Processo Odontoide/lesões , Fraturas da Coluna Vertebral/cirurgia , Adolescente , Adulto , Idoso , Parafusos Ósseos , Pré-Escolar , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Processo Odontoide/diagnóstico por imagem , Radiografia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Centros de Traumatologia
14.
Mar Drugs ; 12(1): 115-27, 2014 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-24394406

RESUMO

Tropical filamentous marine cyanobacteria have emerged as a viable source of novel bioactive natural products for drug discovery and development. In the present study, aplysiatoxin (1), debromoaplysiatoxin (2) and anhydrodebromoaplysiatoxin (3), as well as two new analogues, 3-methoxyaplysiatoxin (4) and 3-methoxydebromoaplysiatoxin (5), are reported for the first time from the marine cyanobacterium Trichodesmium erythraeum. The identification of the bloom-forming cyanobacterial strain was confirmed based on phylogenetic analysis of its 16S rRNA sequences. Structural determination of the new analogues was achieved by extensive NMR spectroscopic analysis and comparison with NMR spectral data of known compounds. In addition, the antiviral activities of these marine toxins were assessed using Chikungunya virus (CHIKV)-infected cells. Post-treatment experiments using the debrominated analogues, namely compounds 2, 3 and 5, displayed dose-dependent inhibition of CHIKV when tested at concentrations ranging from 0.1 µM to 10.0 µM. Furthermore, debromoaplysiatoxin (2) and 3-methoxydebromoaplysiatoxin (5) exhibited significant anti-CHIKV activities with EC50 values of 1.3 µM and 2.7 µM, respectively, and selectivity indices of 10.9 and 9.2, respectively.


Assuntos
Antivirais , Vírus Chikungunya/efeitos dos fármacos , Cianobactérias/química , Toxinas de Lyngbya/farmacologia , Animais , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Relação Dose-Resposta a Droga , Eutrofização , Humanos , Toxinas de Lyngbya/química , Espectroscopia de Ressonância Magnética , Filogenia , Reação em Cadeia da Polimerase , RNA Ribossômico 16S/biossíntese , Ensaio de Placa Viral
15.
Cancer Epidemiol ; 88: 102514, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38141472

RESUMO

OBJECTIVES: Advanced stage is linked to prolonged patient and diagnostic interval for gastrointestinal (GI) cancers. However, objective evidence of this fact is not so forthcoming. Our aim was to study the effect of these intervals on the risk of advanced stage for GI cancers. METHODS: We performed this retrospective cohort study to analyse the effect of patient and diagnostic intervals on final stage in seven types of GI cancers, during 2013 and 2022. Two groups of stage: early (TNM- 0, I, II) and advanced (TNM- III, IV), were formed. Outcome studied was interdependence between patient and diagnostic intervals and incidence of advanced stage. Binary logistic regression was applied to calculate odds ratio of having an advanced versus early stage as a function of duration of these delays, in the whole cohort. We used restricted cubic splines with five knots to study flexible and non-monotonic pattern of association between these delays and stage. RESULTS: In whole cohort of 1859 patients, median patient and diagnostic intervals of early and advanced cancers were 21 and 26 days and 120 and 45 days, respectively. There was a positive association between patient interval and advanced stage (odds ratio [OR], 1.04, confidence interval [CI], 1.035 to 1.045; P < 0.001) and negative association between diagnostic interval and advanced stage (odds ratio, 0.98, CI, 0.976 to 0.998; P-0.017), among all gastrointestinal cancers combined. Increased risk of advanced stage started from day one of patient interval and for diagnostic interval there was an initial decrease followed by subsequent increase in the risk of advanced stage beyond 26 days of diagnostic interval. CONCLUSIONS: Longer patient and diagnostic intervals increase the risk of advanced stage in gastrointestinal cancers.


Assuntos
Detecção Precoce de Câncer , Neoplasias Gastrointestinais , Humanos , Estudos Retrospectivos , Diagnóstico Tardio , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/epidemiologia , Modelos Logísticos
16.
Indian J Otolaryngol Head Neck Surg ; 76(1): 123-129, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38440426

RESUMO

 The primary form of treatment for salivary gland cancer is surgical resection. Radiation therapy is used as adjuvant therapy in cases of aggressive tumours, currently patients with recurrent or metastatic cancer who are not suitable for surgery or radiation are most often treated with chemotherapy. PRISMA guidelines for systematic reviews were followed to evaluate salivary gland malignancies involving cytotoxic chemotherapy and biologic agents. An electronic literature search of Medline, PubMed, Scopus, etc. was performed and relevant articles were selected based on the inclusion criteria. Cytotoxic chemotherapies and biologic drugs such as anti HER - 2, anti-EGFR and anti-C-Kit are used to treat salivary gland cancer. Although most trials have respond poorly to standard chemotherapy with short durability and significant toxicity. Most of the research has focused on ACC and the use of combination therapy with cisplastin in conjunction with other treatments has been found to improve overall survival rate. Due to the limited patient population it was difficult to assess the efficacy of chemotherapy, which achieved very modest results. There are potential molecular targets such as HER2,NTRK and targeted treatments are becoming more popular. However to further explore potential treatment alternatives SGC patients should be enrolled in clinical trials.

17.
Front Med Technol ; 6: 1377443, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39050909

RESUMO

Combination products, amalgamating drugs, biologics, and medical devices, have revolutionized the healthcare landscape with their potential for innovative therapies. However, the intersection of diverse components within these products presents a complex regulatory environment, demanding rigorous attention to safety and efficacy. This article delves into the intricate landscape of regulatory considerations, safety, and efficacy assessments pertaining to combination products-a category at the intersection of drugs, devices, and biologics. The regulatory framework, primarily governed by the U.S. Food and Drug Administration (FDA), necessitates a nuanced classification determining the regulatory pathway. Collaboration between diverse regulatory centers, such as the Center for Drug Evaluation and Research (CDER) and the Center for Devices and Radiological Health (CDRH), underscores the integrated approach required for these innovative healthcare solutions. Safety considerations unravel the potential risks and adverse events associated with combining diverse components, emphasizing the need for robust risk assessment and mitigation strategies. The evaluation of efficacy involves sophisticated methodologies, clinical trials, and post-market surveillance, with recent advancements incorporating digital technologies. This comprehensive exploration aims to contribute to the evolving understanding and best practices in the regulatory and scientific realms, fostering collaboration and innovation in the development and assessment of combination products.

18.
Eur J Nucl Med Mol Imaging ; 40(7): 1025-35, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23525498

RESUMO

PURPOSE: Differentiation between recurrence and radiation necrosis in patients with glioma is crucial, since the two entities have completely different management and prognosis. The purpose of the present study was to compare the efficacies of (18)F-FDG PET/CT and 3,4-dihydroxy-6-[(18)F]fluoro-phenylalanine ((18)F-FDOPA) PET/CT in detection of recurrent gliomas. METHODS: A total of 28 patients (age 38.82 ± 1.25 years; 85.7% men) with histopathologically proven glioma with clinical/imaging suspicion of recurrence were evaluated using (18)F-FDG PET/CT and (18)F-FDOPA PET/CT. (18)F-FDG PET/CT and (18)F-FDOPA PET/CT images were evaluated qualitatively and semiquantitatively. The combination of clinical follow-up, repeat imaging and/or biopsy (when available) was taken as the reference standard. RESULTS: Based on the reference standard, 21 patients were positive and 7 were negative for tumour recurrence. The sensitivity, specificity and accuracy of (18)F-FDG PET/CT were 47.6%, 100% and 60.7%, respectively, and those of (18)F-FDOPA PET/CT were 100%, 85.7% and 96.4%, respectively. The results of (18)F-FDG PET/CT and (18)F-FDOPA PET/CT were concordant in 57.1% of patients (16 of 28) and discordant in 42.9% (12 of 28). The difference in the findings between (18)F-FDG PET/CT and (18)F-FDOPA PET/CT was significant (P = 0.0005, McNemar's test). The difference was significant for low-grade tumours (P = 0.0039) but not for high-grade tumours (P = 0.250). CONCLUSION: (18)F-FDOPA PET/CT is highly sensitive and specific for detection of recurrence in glioma patients. It is superior to (18)F-FDG PET/CT for this purpose and is especially advantageous in patients with low-grade gliomas.


Assuntos
Di-Hidroxifenilalanina/análogos & derivados , Fluordesoxiglucose F18 , Glioma/diagnóstico por imagem , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/normas , Tomografia por Emissão de Pósitrons/normas , Estudos Prospectivos , Recidiva , Padrões de Referência , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/normas , Adulto Jovem
19.
Eur Radiol ; 23(9): 2628-35, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23624623

RESUMO

OBJECTIVES: To compare the diagnostic accuracy of contrast enhanced magnetic resonance imaging (Ce-MRI) and (18)F-fluorodopa ((18)F-FDOPA) positron emission tomography (PET)-computed tomography (CT) for detecting recurrent glioma. METHODS: In this prospective study, 35 patients (age, 36.62 ± 0.86 years; 80 % male) with histopathologically proven glioma with clinical suspicion of recurrence were evaluated using Ce-MRI and (18)F-FDOPA PET-CT. (18)F-FDOPA PET-CT images were evaluated qualitatively and semi-quantitatively. Combination of clinical follow-up (minimum 1 year), repeat imaging and/or biopsy (when available) was taken as the reference standard. RESULTS: Based on the reference standard, 26 patients were positive and nine were negative for recurrence. The sensitivity, specificity and accuracy of Ce-MRI were 92.3 %, 44.4 % and 80 % respectively, whereas those of (18)F-FDOPA PET-CT were 100 %, 88.89 % and 97.1 % respectively. Results of Ce-MRI and (18)F-FDOPA PET-CT were concordant in 74.3 % (29/35) and discordant in 17.1 % of patients (6/35). On McNemar analysis the difference was not statistically significant overall (P = 0.687), for high-grade tumour (P = 0.5) or low-grade tumours (P = 1.0). However, (18)F-FDOPA PET-CT was more specific than Ce-MRI overall (P = 0.0002), for high-grade tumour (P = 0.006) and low-grade tumours (P = 0.004). CONCLUSION: F-FDOPA PET-CT shows a high but comparable diagnostic accuracy to Ce-MRI for the detection of recurrent glioma. However, it is more specific than Ce-MRI. KEY POINTS: • Recurrent glioma in the postoperative site remains a diagnostic dilemma. • (18) F-FDOPA PET-CT shows high diagnostic accuracy for detecting recurrent glioma. • Diagnostic accuracies for (18) F-FDOPA PET-CT and contrast enhanced MRI are comparable. • However, (18) F-FDOPA PET-CT is more specific than Ce-MRI for recurrent glioma.


Assuntos
Neoplasias Encefálicas/patologia , Di-Hidroxifenilalanina/análogos & derivados , Glioma/patologia , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X/métodos , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Meios de Contraste/química , Feminino , Glioma/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento
20.
Childs Nerv Syst ; 29(7): 1215-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23615854

RESUMO

INTRODUCTION: Extrapulmonary skeletal involvement of calvarium in tuberculosis is very uncommon and presentation in an infant has never been reported. It usually presents as a painless scalp swelling, often with a discharging sinus. DISCUSSION: We report here a case of extensive calvarial tuberculosis seen in an infant presenting as exophytic ulcerated growth on the scalp. Differential diagnosis, neuroimaging, and management issues with pertinent literature are reviewed.


Assuntos
Dermatoses do Couro Cabeludo/etiologia , Úlcera Cutânea/etiologia , Crânio/cirurgia , Tuberculose Osteoarticular/complicações , Antituberculosos/uso terapêutico , Craniotomia , Feminino , Humanos , Lactente , Crânio/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Tuberculose Osteoarticular/diagnóstico , Tuberculose Osteoarticular/terapia
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