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1.
Arthritis Care Res (Hoboken) ; 76(8): 1070-1082, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38973729

RESUMO

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.


Assuntos
Doenças Autoimunes , Doenças Pulmonares Intersticiais , Doenças Reumáticas , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Reumáticas/complicações , Doenças Reumáticas/diagnóstico , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Reumatologia/normas , Programas de Rastreamento/normas , Programas de Rastreamento/métodos
2.
Arthritis Rheumatol ; 76(8): 1201-1213, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38973714

RESUMO

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.


Assuntos
Doenças Autoimunes , Doenças Pulmonares Intersticiais , Doenças Reumáticas , Reumatologia , Doenças Pulmonares Intersticiais/diagnóstico , Humanos , Doenças Reumáticas/complicações , Doenças Reumáticas/diagnóstico , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/complicações , Reumatologia/normas , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Testes de Função Respiratória , Tomografia Computadorizada por Raios X , Artrite Reumatoide/complicações , Sociedades Médicas , Estados Unidos , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Doença Mista do Tecido Conjuntivo/complicações , Doença Mista do Tecido Conjuntivo/diagnóstico , Miosite/diagnóstico , Miosite/complicações , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/complicações , Teste de Caminhada
3.
Malays Orthop J ; 18(1): 116-124, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38638669

RESUMO

Introduction: Alleviating pain and anxiety of patients during procedures is an essential skill for an Emergency Physician (EP). Several sedatives and dissociative agents are used for PSA (Procedural Sedation and Analgesia). In this study, we aimed to compare two drugs that is, ketamine and fentanyl for procedural sedation in adults with isolated limb injuries in the Emergency Department (ED). Materials and methods: In this prospective, randomised controlled interventional trial, patients aged between 18 to 65 years with isolated extremity injury requiring PSA in the ED were recruited. A total of 200 subjects were included in the study and randomly allocated to either the fentanyl (n=100) or the ketamine (n=100) group. Patients were blinded to the intervention and subsequently premedicated with Midazolam. Following this, they received either ketamine or fentanyl based on the group they were allocated to. Vital signs, including but not limited to the level of sedation, were measured at predetermined time intervals. A Modified Aldrete Score of >8 was used as a criterion for disposition from the ED. Data were collected in a pre-designed proforma. We aimed to compare the effectiveness as well as ascertain the safety profile of the two drugs for PSA in the ED. Results: There was no significant difference between the two groups when age, gender, mechanism of injury and comorbidities were compared. We found that there was no statistically significant difference between the two groups when blood pressure, respiratory rate and depth of sedation were compared. In both groups, there was a significant decrease in pain on the Numerical Rating Scale (NRS) following drug administration from 8 to 3 (p<0.001). Patients in the fentanyl group had an increased incidence of transient oxygen desaturation (p<0.001). Vomiting was more common in the ketamine group (p<0.001). Conclusion: PSA is a safe and efficacious procedure for patients undergoing painful procedures in ED. Patients in both the groups maintained hemodynamic stability throughout the procedure. From our study, we were able to conclude that both ketamine and fentanyl are similar in efficacy for PSA in the ED for adults with isolated limb injuries. In addition, no significant cardiovascular adverse events were noted in either group in our study.

4.
Clin Exp Dermatol ; 47(3): 516-521, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34480806

RESUMO

Leishmaniasis is broadly classified into three types: cutaneous, mucocutaneous and visceral. The visceral form is most dangerous and can result in death. Although leishmaniasis is an ancient disease, its treatment is still challenging. Several drugs, differing in their cost, toxicity, treatment duration and emergence of drug resistance, are used for different types of leishmaniasis. To overcome these limitations, the search for newer drugs and other treatments continues. In this article, we discuss conventional drugs, other treatments, including newer options such as immunotherapy and immunochemotherapy, and future prospects for leishmaniasis treatment.


Assuntos
Leishmaniose/terapia , Antiprotozoários/uso terapêutico , Terapia Combinada , Crioterapia , Quimioterapia Combinada , Temperatura Alta/uso terapêutico , Humanos , Imunoterapia , Leishmaniose/tratamento farmacológico , Fotoquimioterapia
5.
Clin Oncol (R Coll Radiol) ; 34(3): 172-178, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732295

RESUMO

AIMS: Due to the lack of high-quality evidence and consensus on adjuvant treatment for locoregionally advanced penile cancer, we reviewed the outcomes of pN3 patients to determine the suitable adjuvant treatment options. PATIENTS AND METHODS: All consecutive pN3 penile cancer patients treated at our institution between January 2010 and December 2018 were reviewed to assess the impact of demographical, pathological and treatment factors on disease-free survival (DFS) and overall survival. The DFS and overall survival were estimated using the Kaplan-Meier method and association was tested using the Cox regression model (two-sided test with P < 0.05 considered significant). RESULTS: Of 128 patients, 31 (24%) had pelvic nodal involvement. Twenty-six patients (20.3%) received no adjuvant treatment, 40 (31.3%) received single modality adjuvant treatment and 62 (48.4%) received multimodality adjuvant treatment (a combination of chemotherapy and radiotherapy). At a median follow-up of 22 months, the DFS and overall survival were 55.4 and 62%, respectively. The best DFS and overall survival was noted with chemotherapy followed by concurrent chemoradiation (C-CTRT; 93% each). On multivariate analysis, both DFS and overall survival were worse with pelvic node involvement (2.2 [1.3-4], P = 0.027 and 2.2 [1.3-4], P = 0.027, respectively) and better with any adjuvant treatment (single modality: 3 [1.5-5.5], P < 0.001; multimodality: 3.1 [1.6-6], P < 0.001). C-CTRT was associated with improved DFS over chemotherapy alone (0.17 [0.4-0.78], P = 0.02) but not over radiotherapy alone (0.35 [0.07-1.6], P = 0.19). In patients with no pelvic nodes involved, chemotherapy and radiotherapy as single modalities were associated with similar DFS and overall survival. In patients with pelvic nodes, multimodality treatment was associated with better DFS than single modality treatment (0.3 [0.1-1], P = 0.05). CONCLUSION: pN3 penile cancer is a diverse prognostic group with poorer outcomes associated with pelvic nodes. Single modality adjuvant treatment may be adequate in inguinal nodes with extranodal extension, but multimodality treatment should be given in patients with pelvic nodal involvement.


Assuntos
Neoplasias Penianas , Quimioterapia Adjuvante , Terapia Combinada , Humanos , Linfonodos/patologia , Masculino , Estadiamento de Neoplasias , Pelve/patologia , Neoplasias Penianas/patologia , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos
6.
Ocul Immunol Inflamm ; 30(5): 1186-1189, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33661078

RESUMO

CASE SUMMARY: We present the case of a 50 year old male patient being treated for chronic myeloid leukemia by the tyrosine kinase inhibitor, Ponatinib. After 3 months of treatment, he developed a sight-threatening granulomatous panuveitis in both eyes, with choroidal effusions and neurosensory retinal detachments. Except for a positive interferon-gamma release assay suggesting previous Tuberculosis exposure, all uveitis investigations were normal. Discontinuation of the suspected causative drug led to resolution of signs and a consequent improvement in visual acuity. CONCLUSION: Ponatinib use may be associated with with a uveitic phenotype that is reminiscent of Harada's disease. We compare and contrast this rare ocular phenomenon with Vogt-Koyanagi-Harada syndrome and discuss a possible immunological basis.


Assuntos
Efusões Coroides , Leucemia Mielogênica Crônica BCR-ABL Positiva , Pan-Uveíte , Descolamento Retiniano , Uveíte , Síndrome Uveomeningoencefálica , Humanos , Imidazóis , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Pan-Uveíte/induzido quimicamente , Pan-Uveíte/diagnóstico , Pan-Uveíte/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Piridazinas , Descolamento Retiniano/induzido quimicamente , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/tratamento farmacológico , Uveíte/complicações , Síndrome Uveomeningoencefálica/diagnóstico
7.
Commun Biol ; 4(1): 224, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597720

RESUMO

The endosomal system provides rich signal processing capabilities for responses elicited by growth factor receptors and their ligands. At the single cell level, endosomal trafficking becomes a critical component of signal processing, as exemplified by the epidermal growth factor (EGF) receptors. Activated EGFRs are trafficked to the phosphatase-enriched peri-nuclear region (PNR), where they are dephosphorylated and degraded. The details of the mechanisms that govern the movements of stimulated EGFRs towards the PNR, are not completely known. Here, exploiting the advantages of lattice light-sheet microscopy, we show that EGFR activation by EGF triggers a transient calcium increase causing a whole-cell level redistribution of Adaptor Protein, Phosphotyrosine Interacting with PH Domain And Leucine Zipper 1 (APPL1) from pre-existing endosomes within one minute, the rebinding of liberated APPL1 directly to EGFR, and the dynein-dependent translocation of APPL1-EGF-bearing endosomes to the PNR within ten minutes. The cell spanning, fast acting network that we reveal integrates a cascade of events dedicated to the cohort movement of activated EGF receptors. Our findings support the intriguing proposal that certain endosomal pathways have shed some of the stochastic strategies of traditional trafficking and have evolved processes that provide the temporal predictability that typify canonical signaling.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Cálcio/metabolismo , Dineínas/metabolismo , Endossomos/metabolismo , Microscopia Confocal , Microscopia de Fluorescência , Análise de Célula Única , Proteínas Adaptadoras de Transdução de Sinal/genética , Endossomos/efeitos dos fármacos , Endossomos/genética , Fator de Crescimento Epidérmico/farmacologia , Receptores ErbB/agonistas , Receptores ErbB/genética , Receptores ErbB/metabolismo , Células HeLa , Humanos , Fosforilação , Ligação Proteica , Transporte Proteico , Fatores de Tempo
8.
Eur Rev Med Pharmacol Sci ; 24(10): 5830-5841, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32495923

RESUMO

OBJECTIVE: Recent worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of respiratory coronavirus disease 2019 (COVID-19), is a current, ongoing life-threatening crisis, and international public health emergency. The early diagnosis and management of the disease remains a major challenge. In this review, we aim to summarize the updated epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus SARS-CoV-2. MATERIALS AND METHODS: A broad search of the literature was performed in "PubMed" "Medline" "Web of Science", "Google Scholar" and "World Health Organization-WHO" using the keywords "severe acute respiratory syndrome coronavirus", "2019-nCoV", "COVID-19, "SARS", "SARS-CoV-2" "Epidemiology" "Transmission" "Pathogenesis" "Clinical Characteristics". We reviewed and documented the information obtained from literature on epidemiology, pathogenesis and clinical appearances of SARS-CoV-2 infection. RESULTS: The global cases of COVID-19 as of April 2, 2020, have risen to more than 900,000 and morbidity has reached more than 47,000. The incidence rate for COVID-19 has been predicted to be higher than the previous outbreaks of other coronavirus family members, including those of SARS-CoV and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The main clinical presentation of SARS-CoV-2 infection ranges from asymptomatic stages to severe lower respiratory infection in the form of pneumonia. Most of the patients also presented with fever, cough, sore throat, headache, fatigue, myalgia and breathlessness. Individuals at higher risk for severe illness include elderly people and patients with a weakened immune system or that are suffering from an underlying chronic medical condition like hypertension, diabetes mellitus, cancer, respiratory illness or cardiovascular diseases. CONCLUSIONS: SARS-Cov-2 has emerged as a worldwide threat, currently affecting 170 countries and territories across the globe. There is still much to be understood regarding SARS-CoV-2 about its virology, epidemiology and clinical management strategies; this knowledge will be essential to both manage the current pandemic and to conceive comprehensive measures to prevent such outbreaks in the future.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Enzima de Conversão de Angiotensina 2 , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Líquido da Lavagem Broncoalveolar/virologia , COVID-19 , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/patologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Quarentena , RNA Viral/genética , RNA Viral/metabolismo , SARS-CoV-2 , Escarro/virologia
9.
Acta Gastroenterol Belg ; 83(1): 87-89, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32233278

RESUMO

Azathioprine and 6-mercaptopurine have been widely used for maintenance of remission in patients with inflammatory bowel disease. The use of thiopurines is associated with multiple adverse effects including dose dependent cytopenias or idiosyncratic reaction. We report about a case of azathioprine related pancreatitis associated with polyarthralgia and panniculitis. Pancreatitis, polyarthritis and panniculitis (PPP) syndrome is an uncommon phenomenon which may accompany a number of pancreatic diseases including acute or chronic pancreatitis or pancreatic malignancy. To the best of our knowledge, this is the first report of Azathioprine related PPP syndrome.


Assuntos
Doença de Crohn , Artrite , Azatioprina , Humanos , Imunossupressores , Mercaptopurina , Paniculite
10.
Indian J Tuberc ; 67(1): 112-120, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32192604

RESUMO

Female genital tract tuberculosis (FGTB) is a chronic disease with varied presentation. The diagnosis of FGTB for early institution of treatment remains a clinical challenge. Its laboratory diagnosis is difficult because of paucibacillary nature of the condition and limitation of available diagnostic tests. In view of the intricate problems in diagnosis of FGTB, physicians tend to over treat with empirical anti-tuberculosis drugs. Apart from concerns of drug toxicity, this may be a contributing factor in the increasing incidence of multidrug-resistant TB reported in India. The main goal for advances in TB diagnostics is to reduce delay in diagnosis and treatment. In addition, there should be reduced complexity, improving robustness, and improving accuracy of the laboratory test for diagnosis of Female genital tuberculosis. OBJECTIVE: This narrative review is written with the following objectives. 1) To get a comprehensive overview as well as recent advances in diagnostic test used in the detection of FGTB. 2) To understand the limitations as well as advantages of these laboratory diagnostic test. 3) To provide clinical guidance regarding the detection in susceptible women. METHOD: The literature search was performed using electronic database of Pubmed, Medline, Embase and Google Scholar. Grey literature search was also done. Studies published in English were included. Following keywords were used for search - Tuberculosis, extra pulmonary tuberculosis, female genital tuberculosis, diagnosis of female genital tract tuberculosis. The personal knowledge and experience of authors in the field, helped in archiving the relevant articles. RESULT: Studies suggest that though culture is an invaluable contributor in the diagnosis of FGTB, molecular tests like PCR, LAMP, Xpert MTB/RIF and line probe assays have shown potential and are now being explored to strengthen the diagnostic algorithm of FGTB. CONCLUSION: The use of algorithm approach with combination of both rapid culture and newer molecular techniques will facilitate the accurate and timely diagnosis of FGTB.


Assuntos
Doenças das Tubas Uterinas/diagnóstico , Doenças Ovarianas/diagnóstico , Tuberculose dos Genitais Femininos/diagnóstico , Doenças do Colo do Útero/diagnóstico , Doenças Uterinas/diagnóstico , Algoritmos , Antituberculosos/uso terapêutico , Infecções Assintomáticas , Biópsia , Dor Crônica/etiologia , Dor Crônica/fisiopatologia , Técnicas de Cultura , Endométrio/microbiologia , Endométrio/patologia , Doenças das Tubas Uterinas/complicações , Doenças das Tubas Uterinas/patologia , Doenças das Tubas Uterinas/fisiopatologia , Feminino , Humanos , Histerossalpingografia , Índia , Infertilidade Feminina/etiologia , Infertilidade Feminina/fisiopatologia , Laparoscopia , Distúrbios Menstruais/etiologia , Distúrbios Menstruais/fisiopatologia , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Doenças Ovarianas/complicações , Doenças Ovarianas/patologia , Doenças Ovarianas/fisiopatologia , Dor Pélvica/etiologia , Dor Pélvica/fisiopatologia , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade , Tuberculose dos Genitais Femininos/complicações , Tuberculose dos Genitais Femininos/patologia , Tuberculose dos Genitais Femininos/fisiopatologia , Doenças do Colo do Útero/complicações , Doenças do Colo do Útero/patologia , Doenças do Colo do Útero/fisiopatologia , Doenças Uterinas/complicações , Doenças Uterinas/patologia , Doenças Uterinas/fisiopatologia
11.
Bratisl Lek Listy ; 120(1): 19-25, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30685988

RESUMO

Historically, it was thought that neurogenesis ceased by the end of development, but it is currently understood that neurogenesis continues throughout the life of an individual. This continued growth arises from neural stem or progenitor cells (NSCs) located in specific regions of the adult brain, including the subventricular zone and the dentate gyrus of the hippocampus. Increased understanding of the nature of these cells and their reaction to environmental stimuli is of paramount importance in the effort to discern their role and potential use in repair following neurological disruption. Neurosphere suspension culture is identified as an effective way of actualizing a self-renewing population of neural stem cells. This study demonstrated that adult rat neural stem cells could be effectively induced to differentiate into cells of astrocytic lineage through exposure to fetal bovine serum (FBS), and that the same population of precursor cells could be induced toward neuronal lineage through exposure to dibutyryl cyclic adenosine monophosphate (dcAMP). There were also observations noted regarding difficulty inducing cell attachment following enzymatic digestion of neurospheres, and potential effects on various types of assays, including migration assays (Fig. 7, Ref. 31). Keywords: neural, stem cell, neurosphere, adult rat, cell culture, cell differentiation.


Assuntos
Diferenciação Celular , Células-Tronco Neurais , Neurogênese , Animais , Encéfalo , Células Cultivadas , Ratos
12.
Oral Dis ; 23(8): 1087-1098, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28580710

RESUMO

OBJECTIVE: To generate a nomogram for predicting the risk of neck node metastasis in pathologically node-negative patients using a combination of variables comprising of protein expression, ultrastructural alterations and clinicopathological parameters. MATERIALS AND METHODS: Surgically removed oral tumours (n = 103) were analysed for the expression of desmosomal and hemidesmosomal assembly proteins by immunohistochemistry and ultrastructural alterations by transmission electron microscopy (TEM). Protein expression, ultrastructural alterations and clinicopathological variables were used to construct nomogram from the training set in 75 patients. Clinical utility of the nomogram was validated in a discrete set of 28 patients. RESULTS: Univariate and multivariate analyses were performed on the training set, and obtained significant variables comprising of integrin ß4 expression (p = .027), number of hemidesmosomes (p = .027)/desmosomes (p = .046), tumour differentiation grade (p = .033) and tumour thickness (p = .024) were used for construction of the nomogram. The area under the curve was calculated for both training 0.821 (95% CI 0.725-0.918) and validation sets 0.880 (95% CI 0.743-1.000). The nomogram demonstrated a predictive accuracy of 73.3% and 78.6% with the sensitivity of 81.4% and 83.3% in the training and validation sets, respectively. CONCLUSIONS: The nomogram constructed on postsurgical tumour samples will be a value addition to histopathology for the detection of neck node metastasis in pathologically node-negative patients.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundário , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Nomogramas , Área Sob a Curva , Carcinoma de Células Escamosas/ultraestrutura , Desmossomos/metabolismo , Desmossomos/ultraestrutura , Feminino , Hemidesmossomos/metabolismo , Hemidesmossomos/ultraestrutura , Humanos , Integrina beta4/metabolismo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/ultraestrutura , Pescoço , Gradação de Tumores , Valor Preditivo dos Testes , Curva ROC , Fatores de Risco
13.
Leukemia ; 31(7): 1513-1524, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28210003

RESUMO

Two major types of leukemogenic BCR-ABL fusion proteins are p190BCR-ABLand p210BCR-ABL. Although the two fusion proteins are closely related, they can lead to different clinical outcomes. A thorough understanding of the signaling programs employed by these two fusion proteins is necessary to explain these clinical differences. We took an integrated approach by coupling protein-protein interaction analysis using biotinylation identification with global phosphorylation analysis to investigate the differences in signaling between these two fusion proteins. Our findings suggest that p190BCR-ABL and p210BCR-ABL differentially activate important signaling pathways, such as JAK-STAT, and engage with molecules that indicate interaction with different subcellular compartments. In the case of p210BCR-ABL, we observed an increased engagement of molecules active proximal to the membrane and in the case of p190BCR-ABL, an engagement of molecules of the cytoskeleton. These differences in signaling could underlie the distinct leukemogenic process induced by these two protein variants.


Assuntos
Proteínas de Fusão bcr-abl/fisiologia , Transdução de Sinais/fisiologia , Proteínas do Citoesqueleto/metabolismo , Humanos , Leucemia/etiologia , Fosforilação , Fatores de Transcrição STAT/fisiologia
14.
AAPS PharmSciTech ; 18(6): 2291-2302, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28101725

RESUMO

Hydrogen sulfide (H2S) targets both underlying factors in glaucoma pathogenesis by reducing elevated intraocular pressure (IOP) and providing retinal neuroprotection, whereas the current clinical approaches targets only reducing IOP. Therefore, H2S could be a potential superior candidate for glaucoma pharmacotherapy. However, H2S could be toxic in a concentration greater than 200 µM and its donors are unstable in water. Therefore, this study investigated the preparation and characterization of a non-aqueous in situ gelling sustained-release delivery system for H2S donors. The delivery system was prepared by dissolving GYY 4137, a H2S donor, in poly lactide-co-glycolide polymer (PLGA) (Resomer® RG 502H) solution prepared by dissolving polymer in a mixture of benzyl alcohol and benzyl benzoate in a ratio of 7:3, respectively. The GYY 4137 formulation was characterized for syringeability/injectability, change in pH and tonicity, moisture content, GYY 4137 degradation, and toxicity using rheometer, pH and osmometer, Karl Fisher titrimeter, NMR spectrometer, and Y79 retinoblastoma cells, respectively. The formulation was easily syringeable and injectable as evidenced by rheological data (plastic flow pattern with 43.89 ± 3.21 cP viscosity and 1.12 ± 0.15 Pa yield value). The pH, tonicity, and moisture content values were within acceptable range. NMR spectroscopy indicated presence of 4-methoxyphenylphosphonic acid (GYY 4137 degradation product). The GYY 4137 formulation did not show any significant (p < 0.05) toxicity except the solvent mixture. A sustained release of H2S was observed up to 72 h. The in situ gel forming PLGA-based system can be manipulated to achieve sustained release of H2S from its donor GYY 4137.


Assuntos
Preparações de Ação Retardada , Glaucoma/tratamento farmacológico , Morfolinas/administração & dosagem , Compostos Organotiofosforados/administração & dosagem , Cromatografia Líquida de Alta Pressão , Sulfeto de Hidrogênio/análise , Concentração de Íons de Hidrogênio
15.
Indian J Cancer ; 54(2): 439-441, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29469074

RESUMO

AIMS: : To compare perioperative complications in esophagectomy after neoadjuvant therapy v/s primary surgery. SETTINGS AND DESIGN: : Retrospective analysis of perioperative complications in a prospectively maintained data base of patients who underwent esophagectomy as Primary surgery or after neoadjuvant therapy was done. METHODS AND MATERIAL: : 238 cases of esophagectomies performed for esophageal carcinoma were analysed and compared, out of which 125(52.5%) were given neoadjuvant therapy followed by surgery and 113(47.5%) underwent primary surgery. Surgical procedure was standard for both the groups. All the cases were analysed for perioperative complications. STATISTICAL ANALYSIS USED: : Data was analysed using Open Epi soft ware. Association between the two study group was assessed with Chi square test. RESULTS: : On comparison, both the groups were comparable in demographic profile and type of surgery performed. However, tumour stage was higher for cases who received neoadjuvant therapy as expected. On analysis there was no significant difference in overall morbidity and 30 days mortality. CONCLUSIONS: : Neoadjuvant Chemo/chemoradiotherapy is a feasible option in esophageal carcinoma without increase in incidence of peri operative morbidity or mortality.


Assuntos
Esofagectomia/métodos , Período Perioperatório/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
16.
Indian J Cancer ; 54(Supplement): S65-S66, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29292710

RESUMO

Resistance to 1st or 2nd generation epidermal growth factor receptor (EGFR) - tyrosine kinases (TKIs) develops predominantly due to an acquired mutation, EGFR T790M. Third-generation EGFR-TKIs have demonstrated potent activity against TKI resistance mediated by EGFR T790M. Thus, it become critical to identify T790M mutation on disease progression. Analysis of tumor tissue biopsy material is considered as gold standard for mutation detection. However, lung re-biopsy in a progressed patient involves several challenges - access to tumor, patient's willingness, safety, cost. Minimally invasive plasma circulating tumor DNA (ctDNA) evolved as an alternative for detection of EGFR T790M mutation when tumor genotyping is not feasible. Although a positive T790M result from ctDNA analysis is actionable, caution should be exercised in interpreting negative plasma results. A negative result may imply the absence of a mutation or merely that a patient's tumor is not shedding ctDNA at detectable levels, thus necessitating a confirmatory tissue biopsy to rule out a false negative plasma result. In this case report, we described a 78-year-old female who underwent a reflexed tumor biopsy and tissue based testing upon negative plasma genotyping. Our case report exhibited the importance to follow proposed T790M plasma testing algorithm to screen eligible patients for 3rd generation TKI therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/sangue , Feminino , Genótipo , Humanos , Mutação , Inibidores de Proteínas Quinases/uso terapêutico
17.
J Ophthalmic Vis Res ; 11(4): 385-393, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27994808

RESUMO

PURPOSE: To identify inhibitors that could effectively lower reactive oxygen/nitrogen species (ROS/RNS), complement and inflammatory cytokine levels induced by Benzo(e)pyrene [B(e)p], an element of cigarette smoke, in human retinal pigment epithelial cells (ARPE-19) in vitro. METHODS: ARPE-19 cells were treated for 24 hours with 200 µM, 100 µM, and 50 µM B(e)p or DMSO (dimethyl sulfoxide)-equivalent concentrations. Some cultures were pre-treated with ROS/RNS inhibitors (NG nitro-L-arginine, inhibits nitric oxide synthase; Apocynin, inhibits NADPH oxidase; Rotenone, inhibits mitochondrial complex I; Antimycin A, inhibits mitochondria complex III) and ROS/RNS levels were measured with a fluorescent H2 DCFDA assay. Multiplex bead arrays were used to measure levels of Interleukin-6 (IL-6), Interleukin-8 (IL-8), Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF), Transforming Growth Factor alpha (TGF-α) and Vascular Endothelial Growth Factor (VEGF). IL-6 levels were also measured by an enzyme-linked immunosorbent assay. Real-time qPCR analyses were performed with primers for C3 (component 3), CFH (inhibits complement activation), CD59 (inhibitor of the complement membrane attack complex (MAC)) and CD55/DAF (accelerates decay of target complement target proteins). RESULTS: The ARPE-19 cultures treated with B(e)p showed significantly increased ROS/RNS levels (P < 0.001), which were then partially reversed by 6 µM Antimycin A (19%, P = 0.03), but not affected by the other ROS/RNS inhibitors. The B(e)p treated cultures demonstrated increased levels of IL-6 (33%; P = 0.016) and GM-CSF (29%; P = 0.0001) compared to DMSO-equivalent controls, while the expression levels for components of the complement pathway (C3, CFH, CD59 and CD55/DAF) were not changed. CONCLUSION: The cytotoxic effects of B(e)p include elevated ROS/RNS levels along with pro-inflammatory IL-6 and GM-CSF proteins. Blocking the Qi site of cytochrome c reductase (complex III) with Antimycin A led to partial reduction in B(e)p induced ROS production. Our findings suggest that inhibitors for multiple pathways would be necessary to protect the retinal cells from B(e)p induced toxicity.

19.
Clin Radiol ; 71(10): 941-952, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27450410

RESUMO

The lymphatic system of the abdomen comprises of the cisterna chyli, its major and minor lymphatic tributaries, and lymph nodes. Disorders of the lymphatic system of the abdomen are rarely encountered and consist of primary and secondary types. Abdominal lymphangiomas constitute the majority and have characteristic imaging features. Complicated lymphangiomas may pose a diagnostic dilemma. Generalised systemic lymphangiomatosis is a rare condition and affects major organs with a poor prognosis. Retroperitoneal lymphangiectasia in the appropriate setting might predict underlying infection, such as filariasis. Other acquired conditions include iatrogenic or treatment-induced chylocoele. Chylous ascites can be secondary to multiple causes and can be confirmed by biochemical testing and lymphangiogram in appropriate settings.


Assuntos
Cavidade Abdominal/diagnóstico por imagem , Diagnóstico por Imagem/métodos , Sistema Linfático/diagnóstico por imagem , Humanos
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