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1.
Cell ; 187(20): 5540-5553.e10, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39236707

RESUMO

In 2022, mpox virus (MPXV) spread worldwide, causing 99,581 mpox cases in 121 countries. Modified vaccinia Ankara (MVA) vaccine use reduced disease in at-risk populations but failed to deliver complete protection. Lag in manufacturing and distribution of MVA resulted in additional MPXV spread, with 12,000 reported cases in 2023 and an additional outbreak in Central Africa of clade I virus. These outbreaks highlight the threat of zoonotic spillover by Orthopoxviruses. mRNA-1769, an mRNA-lipid nanoparticle (LNP) vaccine expressing MPXV surface proteins, was tested in a lethal MPXV primate model. Similar to MVA, mRNA-1769 conferred protection against challenge and further mitigated symptoms and disease duration. Antibody profiling revealed a collaborative role between neutralizing and Fc-functional extracellular virion (EV)-specific antibodies in viral restriction and ospinophagocytic and cytotoxic antibody functions in protection against lesions. mRNA-1769 enhanced viral control and disease attenuation compared with MVA, highlighting the potential for mRNA vaccines to mitigate future pandemic threats.


Assuntos
Anticorpos Antivirais , Vacinação , Vaccinia virus , Animais , Vaccinia virus/imunologia , Vaccinia virus/genética , Anticorpos Antivirais/imunologia , Vacinas de mRNA , Mpox/prevenção & controle , Mpox/imunologia , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Anticorpos Neutralizantes/imunologia , Nanopartículas/química , Feminino , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/imunologia , Macaca mulatta , Macaca fascicularis , Lipossomos
2.
Clin Radiol ; 79(6): 460-472, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38614870

RESUMO

BACKGROUND: Several studies have been published comparing deep learning (DL)/machine learning (ML) to radiologists in differentiating PCNSLs from GBMs with equivocal results. We aimed to perform this meta-analysis to evaluate the diagnostic accuracy of ML/DL versus radiologists in classifying PCNSL versus GBM using MRI. METHODOLOGY: The study was performed in accordance with PRISMA guidelines. Data was extracted and interpreted by two researchers with 12 and 23 years' experience, respectively, and QUADAS-2 tool was used for quality and risk-bias assessment. We constructed contingency tables to derive sensitivity, specificity accuracy, summary receiver operating characteristic (SROC) curve, and the area under the curve (AUC). RESULTS: Our search identified 11 studies, of which 8 satisfied our inclusion criteria and restricted the analysis in each study to reporting the model showing highest accuracy, with a total sample size of 1159 patients. The random effects model showed a pooled sensitivity of 0.89 [95% CI:0.84-0.92] for ML and 0.82 [95% CI:0.76-0.87] for radiologists. Pooled specificity was 0.88 [95% CI: 0.84-0.91] for ML and 0.90 [95% CI: 0.81-0.95] for radiologists. Pooled accuracy was 0.88 [95% CI: 0.86-0.90] for ML and 0.86 [95% CI: 0.78-0.91] for radiologists. Pooled AUC of ML was 0.94 [95% CI:0.92-0.96]and for radiologists, it was 0.90 [95% CI: 0.84-0.93]. CONCLUSIONS: MRI-based ML/DL techniques can complement radiologists to improve the accuracy of classifying GBMs from PCNSL, possibly reduce the need for a biopsy, and avoid any unwanted neurosurgical resection of a PCNSL.


Assuntos
Aprendizado Profundo , Glioblastoma , Linfoma , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Humanos , Diagnóstico Diferencial , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Linfoma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Sensibilidade e Especificidade , Radiologistas , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Astrocitoma/diagnóstico por imagem
3.
Clin Radiol ; 76(12): 908-915, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34474747

RESUMO

Colorectal cancer is one of the commonest cancers detected as also amongst the most common causes of cancer death. Survival has improved due to better disease understanding and treatment; however, a substantial proportion of patients recur after curative intent therapy. In this article, we will discuss the imaging features of recurrent colorectal cancer and the role of the radiologist in its management.


Assuntos
Neoplasias Colorretais/terapia , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologia , Humanos , Imageamento por Ressonância Magnética , Metástase Neoplásica/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Ultrassonografia
4.
Neoplasma ; 66(5): 671-680, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31307198

RESUMO

Head and neck paragangliomas Paragangliomas and pheochromocytomas are rare, mostly benign neuroendocrine tumors, which are embryologically derived from neural crest cells of the autonomic nervous system. Paragangliomas are essentially the extra-adrenal counterparts of pheochromocytomas. As such this family of tumors can be subdivided into head and neck paragangliomas, pheochromocytomas and thoracic and abdominal extra-adrenal paragangliomas. Ten out of fifteen genes that contribute to the development of paragangliomas are more susceptible to the development of head and neck paragangliomas when mutated. Gene expression profiling revealed that pheochromocytomas and paragangliomas can be classified into two main clusters (C1 and C2) based on transcriptomes. These groups were defined according to their mutational status and as such strongly associated with specific tumorigenic pathways. The influence of the main genetic drivers on the somatic molecular phenotype was shown by DNA methylation and miRNA profiling. Certain subunits of succinate dehydrogenase (SDHx), von Hippel-Lindau (VHL) and transmembrane protein 127 (TMEM127) still have the highest impact on development of head and neck paragangliomas. The link between RAS proteins and the formation of pheochromocytoma and paragangliomas is clear due to the effect of receptor tyrosine-protein kinase (RET) and neurofibromatosis type 1 (NF1) in RAS signaling and recent discovery of the role of HRAS. The functions of MYC-associated factor X (MAX) and prolyl hydroxylase 2 (PHD2) mutations in the contribution to the pathogenesis of paragangliomas still remain unclear. Ongoing studies give us insight into the incidence of germline and somatic mutations, thus offering guidelines to early detection. Furthermore, these also show the risk of mistakenly assuming sporadic cases in the absence of definitive family history in head and neck paragangliomas.


Assuntos
Neoplasias de Cabeça e Pescoço , Paraganglioma , Humanos , Neoplasias de Cabeça e Pescoço/genética , Mutação , Paraganglioma/genética
5.
Neoplasma ; 64(2): 278-282, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28043156

RESUMO

Pheochromocytomas and Paragangliomas (PHEO/PARA) are rare endocrine tumors originating from the adrenal medulla. More than 20 genes are involved in the tumorigenesis of these tumors, but a substantial part of the causative genetic events remains unexplained. A recent study has reported the presence of the activating BRAF V600E mutation in PCC, suggesting a role for BRAF activation in tumor development. Other studies have not find this mutation. This study investigates the occurrence of the BRAF V600E mutation in these tumors.A cohort of 64 PHEO/PARA were screened for the BRAF V600E mutation using direct Sanger sequencing and QRT-PCR.All cases investigated displayed wild-type without V600E BRAF mutationTaken together with all previously screened tumors up to date, only 1 V600E BRAF mutation has been found among 427 PCCs. These findings imply that the V600E BRAF mutation is a rare event in PHEO/PARA.


Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Paraganglioma/genética , Feocromocitoma/genética , Proteínas Proto-Oncogênicas B-raf/genética , Estudos de Coortes , Humanos , Mutação
6.
Lett Appl Microbiol ; 59(2): 155-60, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24698442

RESUMO

UNLABELLED: The kinetics of cultivation of zygomycete filamentous fungus Rhizopus oryzae in deproteinized whey medium in relation to chitosan production was studied here to optimize chitosan production from R. oryzae as well as utilize whey, a by-product of sweetmeat industry as a cheap source of sugar in the cultivation process. Chitosan content of R. oryzae biomass was found to be increased with time during cultivation and reached maximum (13·6%) after 72 h and then declined steadily. Maximum 1·13 g of chitosan was obtained from one litre of deproteinized whey medium. Concentration of lactose in the medium was observed to be reduced from 45·0 to 11·7 g l(-1) during cultivation resulting in decrease in biochemical oxygen demand (BOD) of whey by approx. 60%, and this was important from environmental point of view before discharging whey into any water body. However, no significant change in pH or titratable acidity was noted during the entire course of cultivation, probably due to good buffering capacity of the medium. Molecular weight of chitosan varied from 130 to 230 kDa depending on the time of cultivation, but no significant change in degree of deacetylation of chitosan (approx. 87%) was found during cultivation. SIGNIFICANCE AND IMPACT OF THE STUDY: Whey is the largest by-product of dairy industries, and its disposal is a big environmental issue because of its high biological oxygen demand (BOD) value. This study will help to lower BOD value of whey by using it as a cultivation medium for fungus R. oryzae that contains chitosan, a very commercially important material on its cell wall. Moreover, the study on biochemical changes in whey during cultivation process with R. oryzae will help to understand the exact changes occurring in the medium and optimize cultivation process to isolate chitosan in larger extent with better and uniform physicochemical properties.


Assuntos
Quitosana/metabolismo , Polissacarídeos Fúngicos/biossíntese , Proteínas do Leite/química , Rhizopus/metabolismo , Meios de Cultura , Giberelinas/química , Giberelinas/metabolismo , Rhizopus/crescimento & desenvolvimento , Proteínas do Soro do Leite
7.
Lett Appl Microbiol ; 58(1): 25-30, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23992047

RESUMO

UNLABELLED: Optimal culture conditions for the production of green pigment was investigated. The optimal culture condition for the production of an extracellular green pigment by growing Bacillus cereus M(1) 16 (MTCC 5521) in a complex medium containing (g l(-1) ) Peptone-4.0, Beef Extract-9.0, NaCl-7.0, MgSO4 .7H2 O-1.0 and KH2 PO4 -5.0 was as follows pH-7.0 at 30°C for 72 h in a 5 l fermenter. Aeration rate and agitator speed had no effect on the pigment production. Thin layer chromatogram of the pigment extracted from the fermented broth with chloroform on silica gel GF254 using ethyl acetate and hexane (1 : 1) as solvent showed three fractions. The major fraction (C3 ) was separated out and identified as 9-methyl-1, 4, 5, 8-tetra-azaphenanthrene. Acute toxicity test revealed the nontoxic nature upto a dose of 2000 mg kg(-1) , b.wt., of mice. MTT assay showed the cytotoxic nature in HL60 cells having an IC50 of 2.47 mmol. So, this biopigment may have application in food, textile colorant and pharmaceutical industry. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated the optimum production of a biopigment (9-methyl-1, 4, 5, 8-tetra-azaphenanthrene) by fermentation of a complex medium with Bacillus cereus M(1) 16 (MTCC 5521) in submerged fermentation. This is the first investigation of toxicity and cytotoxicity activities of this biopigment. The study showed that the purified pigment had no toxicity to healthy albino mice but a high cytotoxicity activity in HL60 cancer cell line in vitro. The biopigment had further displayed dyeing capability to both solidified agar and cotton cloth. Therefore, it may represent a nontoxic and natural alternative to chemical dyes and pigments.


Assuntos
Bacillus cereus/metabolismo , Fermentação , Fenantrenos/metabolismo , Pigmentos Biológicos/biossíntese , Animais , Reatores Biológicos , Meios de Cultura , Células HL-60 , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Fenantrenos/farmacologia , Fenantrenos/toxicidade , Pigmentos Biológicos/isolamento & purificação , Pigmentos Biológicos/farmacologia , Pigmentos Biológicos/toxicidade
8.
Foot Ankle Surg ; 18(1): 50-4, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22326005

RESUMO

BACKGROUND: The bunionette or tailor's bunion is a lateral prominence of the fifth metatarsal head. It is usually characterised by a wide intermetatarsal angle (IMA) between the 4th and 5th metatarsals, varus of the metatarsophalangeal (MTP) joint, pain and callus formation. Various distal, shaft and basal osteotomies have been described in the literature. We have described a reverse scarf osteotomy for bunionette correction. PATIENTS AND METHODS: We have used a 'reverse' scarf osteotomy in 12 cases (10F: 2M) with a mean follow-up of 12 months (range 5-22 months) with radiographs and clinical scoring. RESULTS: Post operatively, mean IMA improved from 13.1° to 7.27° (range 2.0-11.5°); mean 5th MTP angle improved from 19.9° to 6.36° (range 2.8-9.0°) and postoperative mean AOFAS improved from 54.25 to 89.58 (range 70-100). CONCLUSION: 'Reverse' scarf osteotomy in the correction of bunionette deformity offers promising results in the short term.


Assuntos
Joanete do Alfaiate/cirurgia , Articulação Metatarsofalângica/cirurgia , Osteotomia/métodos , Adulto , Idoso , Joanete do Alfaiate/diagnóstico por imagem , Joanete do Alfaiate/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Articulação Metatarsofalângica/diagnóstico por imagem , Articulação Metatarsofalângica/fisiopatologia , Pessoa de Meia-Idade , Período Pós-Operatório , Radiografia , Amplitude de Movimento Articular , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
9.
ESMO Open ; 6(5): 100252, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34461483

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause life-threatening cardiovascular adverse events (CVAEs) that may not be attributed to therapy. The outcomes of clinical trials may underestimate treatment-related adverse events due to restrictive eligibility, limited sample size, and failure to anticipate selected toxicities. We evaluated the incidence and clinical determinants of CVAEs in real-world population on ICI therapy. PATIENTS AND METHODS: Among 2 687 301 patients diagnosed with cancer from 2011 to 2018, 16 574 received ICIs for any cancer. Patients in the ICI and non-ICI cohorts were matched in a 1 : 1 ratio according to age, sex, National Cancer Institute comorbidity score, and primary cancer. The non-ICI cohort was stratified into patients who received chemotherapy (N = 2875) or targeted agents (N = 4611). All CVAEs, non-cardiac immune-related adverse events occurring after treatment initiation, baseline comorbidities, and treatment details were identified and analyzed using diagnosis and billing codes. RESULTS: Median age was 61 and 65 years in the ICI and non-ICI cohorts, respectively (P < 0.001). ICI patients were predominantly male (P < 0.001). Lung cancer (43.1%), melanoma (30.4%), and renal cell carcinoma (9.9%) were the most common cancer types. CVAE diagnoses in our dataset by incidence proportion (ICI cohort) were stroke (4.6%), heart failure (3.5%), atrial fibrillation (2.1%), conduction disorders (1.5%), myocardial infarction (0.9%), myocarditis (0.05%), vasculitis (0.05%), and pericarditis (0.2%). Anti-cytotoxic T-lymphocyte-associated protein 4 increased the risk of heart failure [versus anti-programmed cell death protein 1; hazard ratio (HR), 1.9; 95% confidence interval (CI) 1.27-2.84] and stroke (HR, 1.7; 95% CI 1.3-2.22). Pneumonitis was associated with heart failure (HR, 2.61; 95% CI 1.23-5.52) and encephalitis with conduction disorders (HR, 4.35; 95% CI 1.6-11.87) in patients on ICIs. Advanced age, primary cancer, nephritis, and anti-cytotoxic T-lymphocyte-associated protein 4 therapy were commonly associated with CVAEs in the adjusted Cox proportional hazards model. CONCLUSIONS: Our findings underscore the importance of risk stratification and cardiovascular monitoring for patients on ICI therapy.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Neoplasias Pulmonares , Melanoma , Idoso , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia
10.
J Exp Med ; 169(6): 1961-76, 1989 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-2471770

RESUMO

T cell-mediated immune response against autologous melanoma cells was analyzed, at population and clonal levels, in 31 patients with recurrent and/or metastatic disease. Fresh PBL and lymph node lymphocytes (LNL) from melanoma-involved nodes were not cytotoxic against the respective melanoma cells. When activated in in vitro coculture (IVC) against the autologous melanoma cells in the presence of IL-2, a majority of the activated PBL and LNL became cytotoxic against the autologous targets. The activated effector cells were cloned in limiting dilution microcultures, and growing clones were phenotypically defined and were functionally characterized for cytotoxicity and for potential regulatory function. Functional T cell clones were obtained from 15 of 31 cases. Of these, CTL responses exhibiting cytotoxicity restricted against the autologous melanoma were seen in four cases. All four CTL clones were CD3+, CD8+, and CD4-. Three of these four CTL clones were studied extensively. All three of these CTL clones expressed MHC class I-restricted cytotoxicity. mAb anti-CD3 blocked cytotoxicity in two and enhanced cytotoxicity in the other. Neither autologous sera nor autologous nonactivated fresh PBL modulated the cytotoxic functions of the CTL clones at the effector phase. T cell lines exhibiting regulatory function were obtained in 11 cases. The regulatory T cell lines were CD3+, CD4+, and CD8-. In three cases CD4+ clones amplified the cytotoxic response in the PBL in coculture, while in eight other cases the T cell lines downregulated the cytotoxic responses. Such T cell-mediated down-regulations were either restricted to the autologous system, induced by D/DR antigens expressed by the autologous or allogeneic melanoma cells, or induced by stimulus other than D/DR antigens. Taken together, these findings clearly demonstrate the existence of T cell-mediated cytotoxic and regulatory responses against human melanoma.


Assuntos
Células Clonais/imunologia , Testes Imunológicos de Citotoxicidade , Melanoma/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T/imunologia , Antígenos de Neoplasias/imunologia , Linhagem Celular , Sobrevivência Celular , Células Clonais/fisiologia , Testes Imunológicos de Citotoxicidade/métodos , Citotoxicidade Imunológica , Epitopos/imunologia , Humanos , Interferon gama/fisiologia , Interleucina-2/fisiologia , Antígenos Específicos de Melanoma , Proteínas de Neoplasias/imunologia , Linfócitos T/fisiologia , Linfócitos T Citotóxicos/fisiologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia
11.
Hum Mutat ; 29(1): 74-82, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17960768

RESUMO

About 10% of neurofibromatosis type 1 (NF1) patients develop malignant peripheral nerve sheath tumors (MPNSTs) and represent considerable patient morbidity and mortality. Elucidation of the genetic mechanisms by which inherited and acquired NF1 disease gene variants lead to MPNST development is important. A study was undertaken to identify the constitutional and somatic NF1 mutations in 34 MPNSTs from 27 NF1 patients. The NF1 germline mutations identified in 22 lymphocytes DNA from these patients included seven novel mutations and a large 1.4-Mb deletion. The NF1 germline mutation spectrum was similar to that previously identified in adult NF1 patients without MPNST. Somatic NF1 mutations were identified in tumor DNA from 31 out of 34 MPNSTs, of which 28 were large genomic deletions. The high prevalence (>90%) of such deletions in MPNST contrast with the =or<20% found in benign neurofibromas and is indicative of the involvement of different mutational mechanisms in these tumors. Coinactivation of the TP53 gene by deletion, or by point mutation along with NF1 gene inactivation, is known to exacerbate disease symptoms in NF1, therefore TP53 gene inactivation was screened. DNA from 20 tumors showed evidence for loss of heterozygosity (LOH) across the TP53 region in 11 samples, with novel TP53 point mutations in four tumors.


Assuntos
Mutação em Linhagem Germinativa , Mutação , Neoplasias de Bainha Neural/genética , Neurofibromina 1/genética , Neoplasias do Sistema Nervoso Periférico/genética , Adulto , Análise Mutacional de DNA , DNA de Neoplasias/metabolismo , Humanos , Perda de Heterozigosidade , Linfócitos/metabolismo , Neurofibromina 1/metabolismo , Deleção de Sequência , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
12.
Colloids Surf B Biointerfaces ; 62(2): 173-9, 2008 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-17997083

RESUMO

The husk of Lathyrus sativus (HLS) has been functionalized by introducing thio groups with the help of carbon disulphide treatment in alkaline environment. Elemental analysis indicates that sulphur content of the functionalized biomass increases to 3.7% from 0.36% of the pristine biomass suggesting the incorporation of thio group on HLS. A conspicuous change in the surface morphology of the biomass due to functionalization is depicted by SEM images. EDX data support the introduction of sulphur group on the HLS. The involvement of the hydroxyl groups mainly in the functionalization process is demonstrated by Fourier transform infrared (FTIR) spectroscopic study. The adsorption capacity of the functionalized biomass with respect to cadmium and nickel is observed to increase by about 50% compared to that of pristine one. Similar to the case of unmodified HLS the adsorption process involving the functionalized one obeys Langmuir isotherm model and attains equilibrium in 10 min compared with 60 min in the case of unmodified biomass.


Assuntos
Cádmio/química , Lathyrus/química , Níquel/química , Adsorção , Algoritmos , Biomassa , Indicadores e Reagentes , Cinética , Microscopia Eletrônica de Varredura , Folhas de Planta/química , Polissacarídeos Bacterianos/química , Soluções , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica , Difração de Raios X
13.
Clin Otolaryngol ; 33(3): 255-9, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18559034

RESUMO

Seventy-two patients with a unilateral vestibular schwannoma have been treated conservatively for a median of 121 months. They have been followed prospectively by serial clinical examination, MRI scans and audiometry. Twenty-five patients (35%, 95% CI: 24-47) failed conservative management and required active intervention during the study. No factors predictive of tumour growth or failure of conservative management could be identified. Seventy-five per cent of failures occurred in the first half of the 10-year study. The median growth rate for all tumours at 10 years was 1 mm/year (range -0.53-7.84). Cerebellopontine angle tumours grew faster (1.4 mm/year) than intracanalicular tumours (0 mm/year, P < 0.01); 92% had growth rates under 2 mm/year. Hearing deteriorated substantially even in tumours that did not grow, but did so faster in tumours that grew significantly (mean deterioration in pure tone average at 0.5, 1, 2 and 3 kHz was 36 dB; speech discrimination scores deteriorated by 40%). Patients who failed conservative management had clinical outcomes that were not different from those who underwent primary treatment without a period of conservative management.


Assuntos
Neuroma Acústico/terapia , Adulto , Idoso , Audiometria , Feminino , Audição , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroma Acústico/diagnóstico , Neuroma Acústico/patologia , Neuroma Acústico/fisiopatologia , Estudos Prospectivos , Falha de Tratamento
14.
J Stomatol Oral Maxillofac Surg ; 119(3): 212-215, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29475080

RESUMO

Ameloblastoma represents the most common epithelial odontogenic tumor. Because of the proximity of the maxillary tumors to the orbit and skull base, it should be managed as radically as possible. Maxillectomy, mainly via the transfacial or transoral approach, represents the most common type of surgical procedure. Drawback of these approaches is limited control of the superiomedial extent of the tumour in the paranasal area. We report the use of a combined endoscopic endonasal and transoral approach to manage maxillary plexiform ameloblastoma in a 48-year-old male patient. A combined endoscopic endonasal and transoral approach enabled the radical removal of tumour with a 1.5cm margin of radiographically intact bone with good control from both intrasinusal and intraoral aspects. Adequate visualization of the extent of the lesion (e.g. orbit, infratemporal fossa, anterior cranial base) had been achieved. Non-complicated healing was achieved. This technique of partial maxillectomy led to very good aesthetic and functional results. No recurrence had been noted during review appointments. The combination of endoscopic endonasal and transoral approach for a partial maxillectomy allows sufficient reduction of the defect, thus eliminating the necessity for reconstruction and reducing the morbidity associated with it.


Assuntos
Ameloblastoma , Seios Paranasais , Estética Dentária , Humanos , Masculino , Maxila , Pessoa de Meia-Idade , Recidiva Local de Neoplasia
15.
J Clin Invest ; 91(2): 547-52, 1993 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8432863

RESUMO

Tissue factor (TF) is a low molecular weight glycoprotein that initiates the clotting cascade and is considered to be a major regulator of coagulation, hemostasis, and thrombosis. TF is not expressed in the intima or media of normal adult blood vessels. Accordingly, it has been hypothesized that the initiation of intravascular coagulation may require the "induced" expression of TF in the vessel wall. We report that TF mRNA and protein are rapidly and markedly induced in early and late passaged vascular smooth muscle cells (VSMC) by growth factors (serum, platelet-derived growth factor, epidermal growth factor), vasoactive agonists (angiotensin II), and a clotting factor (alpha-thrombin). The induction of TF mRNA by these agents is dependent upon mobilization of intracellular Ca2+ and is blocked by Ca2+ chelation. In contrast to other growth factor-responsive genes, such as KC and c-fos, downregulation of protein kinase C activity by prolonged treatment with phorbol esters fails to block agonist-mediated TF induction. This raises the possibility that protein kinase C activation may not be necessary for TF mRNA induction in VSMC. VSMC may play a role in the generation or propagation of thrombus through the induction of TF, particularly in settings, such as those associated with acute vessel injury, where the endothelium is denuded and the VSMC are exposed to circulating blood.


Assuntos
Cálcio/metabolismo , Músculo Liso Vascular/metabolismo , Proteína Quinase C/metabolismo , Tromboplastina/biossíntese , Angiotensina II/farmacologia , Animais , Células Cultivadas , Ativação Enzimática , Masculino , Fator de Crescimento Derivado de Plaquetas/farmacologia , RNA Mensageiro/biossíntese , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Trombina/farmacologia , Tromboplastina/genética
16.
J Clin Invest ; 91(5): 2253-9, 1993 May.
Artigo em Inglês | MEDLINE | ID: mdl-7683701

RESUMO

Tissue factor (TF) is a major activator of the coagulation cascade and may play a role in initiating thrombosis after intravascular injury. To investigate whether medial vascular smooth muscle provides a source of TF following arterial injury, the induction of TF mRNA and protein was studied in balloon-injured rat aorta. After full length aortic injury, aortas were harvested at various times and the media and adventitia separated using collagenase digestion and microscopic dissection. In uninjured aortic media, TF mRNA was undetectable by RNA blot hybridization. 2 h after balloon injury TF mRNA levels increased markedly. Return to near baseline levels occurred at 24 h. In situ hybridization with a 35S-labeled antisense rat TF cRNA probe detected TF mRNA in the adventitia but not in the media or endothelium of uninjured aorta. 2 h after balloon dilatation, a marked induction of TF mRNA was observed in the adventitia and media. Using a functional clotting assay, TF procoagulant activity was detected at low levels in uninjured rat aortic media and rose by approximately 10-fold 2 h after balloon dilatation. Return to baseline occurred within 4 d. These data demonstrate that vascular injury rapidly induces active TF in arterial smooth muscle, providing a procoagulant that may result in thrombus initiation or propagation.


Assuntos
Aorta Torácica/metabolismo , Aorta Torácica/patologia , Cateterismo/efeitos adversos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , RNA Mensageiro/biossíntese , Tromboplastina/biossíntese , Animais , Aorta Torácica/lesões , Células Cultivadas , Sondas de DNA , Embolia/metabolismo , Embolia/patologia , Biblioteca Gênica , Hibridização In Situ , Cinética , Masculino , Músculo Liso Vascular/lesões , RNA/genética , RNA/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Valores de Referência , Tromboplastina/genética , Fatores de Tempo
17.
Mol Cell Biol ; 13(12): 7203-12, 1993 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8246942

RESUMO

Malignant astrocytoma is the most common primary human brain tumor. Most astrocytomas express a combination of platelet-derived growth factor (PDGF) and PDGF receptor which could close an autocrine loop. It is not known whether these autocrine loops contribute to the transformed phenotype of astrocytoma cells or are incidental to that phenotype. Here we show that dominant-negative mutants of the PDGF ligand break the autocrine loop and revert the phenotype of BALB/c 3T3 cells transformed by the PDGF-A or PDGF-B (c-sis) gene. Then, we show that these mutants are selective in that they do not alter the phenotype of 3T3 cells transformed by an activated Ha-ras or v-src gene or by simian virus 40. Finally, we show that these mutants revert the transformed phenotype of two independent human astrocytoma cell lines. They have no effect on the growth of human medulloblastoma, bladder carcinoma, or colon carcinoma cell lines. These observations are consistent with the view that PDGF autocrine loops contribute to the transformed phenotype of at least some human astrocytomas.


Assuntos
Astrocitoma/genética , Mutação , Fator de Crescimento Derivado de Plaquetas/genética , Células 3T3 , Animais , Astrocitoma/patologia , Adesão Celular/genética , Divisão Celular/efeitos dos fármacos , Transformação Celular Neoplásica/genética , DNA Complementar/genética , Genes Dominantes , Humanos , Camundongos , Camundongos Nus , Transplante de Neoplasias , Fenótipo , Transformação Genética , Transplante Heterólogo , Células Tumorais Cultivadas/patologia
18.
Colloids Surf B Biointerfaces ; 57(2): 135-42, 2007 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-17395437

RESUMO

Husk of Lathyrus sativus (HLS) has been found to be a good sorbent for the removal of nickel(II) from its aqueous solution. The adsorption process depends on pH of the solution with an optimum at 5.0, and follows Langmuir isotherm model (correlation coefficient 0.998). Initial adsorption rate is very fast and reaches equilibrium following pseudo-second order kinetics within 60 min. Amino, carboxyl, hydroxyl and phosphate groups of the biomass are involved in chemical interaction with nickel ions as revealed from SEM-EDX and FTIR studies. Chemical modifications of the functional groups of the biosorbent show that amino groups contribute largely (approximately 57%) for the binding of nickel ions and probably undergo chelation through dative bond formation. HLS biomass has been found to adsorb both nickel and cadmium equally from their mixed solution to the extent of approximately 70% indicating the importance of this sorbent in industrial effluent treatment.


Assuntos
Recuperação e Remediação Ambiental/métodos , Lathyrus/química , Níquel/química , Adsorção , Concentração de Íons de Hidrogênio , Cinética , Microscopia Eletrônica de Varredura , Níquel/isolamento & purificação , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura
19.
Int J Oral Maxillofac Surg ; 46(1): 111-115, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27726907

RESUMO

Septic arthritis of the temporomandibular joint (TMJ) is an unusual disease in adults. Inoculation of the pathogen may occur through traumatic or iatrogenic injuries, or more often by haematogenous spread from a distant focus. The cause of infection is unknown in most cases. A case of ostensibly mild septic arthritis of the TMJ with a good response to antibiotic therapy and lavage, but that finally led to fatal destruction of the joint structures in a 38-year-old female patient, is reported herein. The infection was caused by Raoultella ornithinolytica - a rare bacterial species in humans, which has not been reported previously in any patients with joint problems. The arthritis manifested 5 weeks after an arthroscopy procedure, so the cause was not clear.


Assuntos
Antibacterianos/uso terapêutico , Artrite Infecciosa/microbiologia , Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/isolamento & purificação , Transtornos da Articulação Temporomandibular/microbiologia , Articulação Temporomandibular/microbiologia , Adulto , Artrite Infecciosa/diagnóstico por imagem , Artrite Infecciosa/tratamento farmacológico , Artroplastia de Substituição , Diagnóstico Diferencial , Infecções por Enterobacteriaceae/diagnóstico por imagem , Infecções por Enterobacteriaceae/tratamento farmacológico , Feminino , Humanos , Imageamento por Ressonância Magnética , Radiografia Panorâmica , Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/tratamento farmacológico , Transtornos da Articulação Temporomandibular/cirurgia , Irrigação Terapêutica
20.
Ann R Coll Surg Engl ; 99(5): 347-350, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27917666

RESUMO

INTRODUCTION According to the National Confidential Enquiry into Perioperative Deaths (NCEPOD), out-of-hours operating in trauma and orthopaedics should be reserved for life or limb threatening cases only. The aim of our study was to determine the nature of non-emergency work carried out in our trust at night in 2015. The overall efficacy and clinical safety of the services provided was evaluated. METHODS Surgical activity undertaken after 9pm was reviewed along with patient ASA (American Society of Anesthesiologists) grade, grade of operating surgeon and any complications that occurred following the procedure. Furthermore, the clinical urgency and safety of cases was assessed based on whether there was any record of life or limb threatening indications at the time of admission. RESULTS Overall, 131 procedures were performed after 9pm, with 102 performed between 9pm and midnight, and 29 after midnight. Consultants performed 16 cases and the remaining 115 cases were operated on by middle grades or specialty trainees. A fifth (20%) of the cases were genuinely life or limb threatening. A total of 123 procedures were classed as having good outcomes. The complication rate was 8%. CONCLUSIONS In our study, 80% of the procedures performed after 9pm could not be categorised as life or limb threatening. Appropriate NCEPOD classification would ensure that only life or limb threatening cases were listed for theatre after 9pm. Alternative methods of operating within working hours should be considered.


Assuntos
Salas Cirúrgicas/estatística & dados numéricos , Procedimentos Ortopédicos/estatística & dados numéricos , Segurança do Paciente , Adolescente , Adulto , Fraturas Ósseas/cirurgia , Hospitais de Distrito , Hospitais Gerais , Humanos , Fatores de Tempo , Adulto Jovem
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