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1.
J Hematol Oncol ; 13(1): 131, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008453

RESUMO

SARS-CoV-2 has infected millions of people worldwide, but little is known at this time about second infections or reactivation. Here, we report a case of a 55-year-old female undergoing treatment for CD20+ B cell acute lymphoblastic leukemia who experienced a viral reactivation after receiving rituximab, cytarabine, and dasatinib. She was initially hospitalized with COVID-19 in April and developed a high antibody titer with two negative nasal polymerase chain reaction (PCR) swabs for SARS-CoV-2 on discharge. After recovery, she resumed treatment in June for her leukemia, which included rituximab, cytarabine, and dasatinib. She promptly lost her COVID-19 antibodies, and her nasal PCR turned positive in June. She developed a severe COVID-19 pneumonia with lymphopenia, high inflammatory markers, and characteristic bilateral ground-glass opacities on chest CT, requiring high-flow nasal cannula and transfer to the intensive care unit. She received steroids, anticoagulation, and convalescent plasma, and within 48 h she was off oxygen. She was discharged home in stable condition several days later. Given the short time frame from leukemia treatment to PCR positivity and the low case rate in mid-June in New York City, reinfection appears to have been unlikely and SARS-CoV-2 reactivation is a possible explanation. This case illustrates the risks of treating recently recovered COVID-19 patients with immunosuppressive therapy, particularly lymphocyte- and antibody-depleting therapy, and raises new questions about the potential of SARS-CoV-2 reactivation.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/imunologia , Citarabina/uso terapêutico , Imunossupressores/uso terapêutico , Pneumonia Viral/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Rituximab/uso terapêutico , Doença Aguda , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Anticoagulantes/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Citarabina/efeitos adversos , Feminino , Humanos , Imunização Passiva , Imunossupressores/efeitos adversos , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Reação em Cadeia da Polimerase , Recidiva , Rituximab/efeitos adversos , Esteroides/uso terapêutico , Resultado do Tratamento
2.
Klin Monbl Augenheilkd ; 237(10): 1177-1186, 2020 Oct.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-33059377

RESUMO

Childhood uveitis is an ophthalmological challenge, since on the one hand it often remains asymptomatic and difficult to detect, and on the other hand it often has a chronic course and is associated with a high risk of complications threatening the vision. The most important risk factors for childhood uveitis are underlying rheumatic diseases; recommendations for ophthalmological monitoring have been developed together with paediatric rheumatologists. Intermediate and posterior uveitis are rare in children. The therapy must effectively control inflammation and at the same time cause only minimal side effects. Since steroids in particular cause side effects frequently, an immunosuppressive therapy must be initiated early in an interdisciplinary cooperation with paediatric rheumatologists and parents with the goal of minimising steroids.


Assuntos
Artrite Juvenil , Oftalmologia , Uveíte Posterior , Uveíte , Criança , Humanos , Esteroides , Uveíte/diagnóstico , Uveíte/tratamento farmacológico
4.
Pediatrics ; 146(4)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32943536

RESUMO

OBJECTIVES: To evaluate the survival and neurodevelopmental impairment (NDI) in extremely low birth weight (ELBW) infants at 18 to 26 months with early hypoxemic respiratory failure (HRF). We also assessed whether African American infants with early HRF had improved outcomes after exposure to inhaled nitric oxide (iNO). METHODS: ELBW infants ≤1000 g and gestational age ≤26 weeks with maximal oxygen ≥60% on either day 1 or day 3 were labeled as "early HRF" and born between 2007 and 2015 in the Neonatal Research Network were included. Using a propensity score regression model, we analyzed outcomes and effects of exposure to iNO overall and separately by race. RESULTS: Among 7639 ELBW infants born ≤26 weeks, 22.7% had early HRF. Early HRF was associated with a mortality of 51.3%. The incidence of moderate-severe NDI among survivors was 41.2% at 18 to 26 months. Mortality among infants treated with iNO was 59.4%. Female sex (adjusted odds ratio [aOR]: 2.4, 95% confidence interval [CI]: 1.8-3.3), birth weight ≥720 g (aOR: 2.3, 95% CI: 1.7-3.1) and complete course of antenatal steroids (aOR: 1.6, 95% CI: 1.1-2.2) were associated with intact survival. African American infants had a similar incidence of early HRF (21.7% vs 23.3%) but lower exposure to iNO (16.4% vs 21.6%). Among infants with HRF exposed to iNO, intact survival (no death or NDI) was not significantly different between African American and other races (aOR: 1.5, 95% CI: 0.6-3.6). CONCLUSIONS: Early HRF in infants ≤26 weeks' gestation is associated with high mortality and NDI at 18 to 26 months. Use of iNO did not decrease mortality or NDI. Outcomes following iNO exposure were not different in African American infants.


Assuntos
Broncodilatadores/uso terapêutico , Hipóxia/complicações , Lactente Extremamente Prematuro , Transtornos do Neurodesenvolvimento/epidemiologia , Óxido Nítrico Sintase Tipo II/uso terapêutico , Insuficiência Respiratória/mortalidade , Administração por Inalação , Afro-Americanos , Índice de Apgar , Peso ao Nascer , Broncodilatadores/administração & dosagem , Feminino , Ruptura Prematura de Membranas Fetais , Mortalidade Hospitalar , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Incidência , Lactente , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Masculino , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/tratamento farmacológico , Transtornos do Neurodesenvolvimento/etnologia , Óxido Nítrico Sintase Tipo II/administração & dosagem , Alta do Paciente , Gravidez , Pontuação de Propensão , Insuficiência Respiratória/tratamento farmacológico , Insuficiência Respiratória/etnologia , Insuficiência Respiratória/etiologia , Fatores de Risco , Fatores Sexuais , Esteroides/uso terapêutico
5.
J Assoc Physicians India ; 68(10): 66-67, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32978929

RESUMO

We here report a case of Takayasu arteritis who came to us with uncontrolled hypertension, arm claudication and a history of Pott's spine (treated). She was treated with steroids which led to significant improvement in the patient's clinical profile.


Assuntos
Hipertensão , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/tratamento farmacológico , Tuberculose , Feminino , Humanos , Esteroides
6.
J Endocrinol ; 247(2): R45-R62, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32966970

RESUMO

Coronavirus disease (COVID-19) is caused by a new strain of coronavirus, the severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2. At the time of writing, SARS-CoV-2 has infected over 5 million people worldwide. A key step in understanding the pathobiology of the SARS-CoV-2 was the identification of -converting enzyme 2 (ACE2) as the receptor for SARS-CoV-2 to gain entry into host cells. ACE2 is an established component of the 'protective arm' of the renin-angiotensin-aldosterone-system (RAAS) that opposes ACE/angiotensin II (ANG II) pressor and tissue remodelling actions. Identification of ACE2 as the entry point for SARS-CoV-2 into cells quickly focused attention on the use of ACE inhibitors (ACEi), angiotensin receptor blockers (ARB) and mineralocorticoid receptor antagonists (MRA) in patients with hypertension and cardiovascular disease given that these pharmacological agents upregulate ACE2 expression in target cells. ACE2 is cleaved from the cells by metalloproteases ADAM10 and ADAM17. Steroid hormone receptors regulate multiple components of the RAAS and may contribute to the observed variation in the incidence of severe COVID-19 between men and women, and in patients with pre-existing endocrine-related disease. Moreover, glucocorticoids play a critical role in the acute and chronic management of inflammatory disease, independent of any effect on RAAS activity. Dexamethasone, a synthetic glucocorticoid, has emerged as a life-saving treatment in severe COVID-19. This review will examine the endocrine mechanisms that control ACE2 and discusses the impact of therapies targeting the RAAS, glucocorticoid and other endocrine systems for their relevance to the impact of SARS-CoV-2 infection and the treatment and recovery from COVID-19-related critical illness.


Assuntos
Aldosterona/metabolismo , Betacoronavirus/fisiologia , Infecções por Coronavirus/enzimologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/enzimologia , Sistema Renina-Angiotensina , Esteroides/metabolismo , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Animais , Betacoronavirus/genética , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Humanos , Pandemias , Peptidil Dipeptidase A/genética , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo
7.
PLoS One ; 15(9): e0237523, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32870918

RESUMO

BACKGROUND: Meniere's disease (MD) is a chronic condition of the inner ear consisting of symptoms that include vertigo attacks, fluctuating sensorineural hearing loss, tinnitus and aural fullness. Despite availability of various interventions, there is uncertainty surrounding their relative efficacy, thus making it difficult to select the appropriate treatments for MD. The objective of this systematic review was to assess the relative effects of the available pharmacologic and surgical interventions in patients with MD with regard to vertigo and other key patient outcomes based on data from randomized clinical trials (RCTs). METHODS: Our published protocol registered with PROSPERO (CRD42019119129) provides details on eligibility criteria and methods. We searched various databases including MEDLINE, Embase and the Cochrane Library from inception to December 10th, 2018. Screening at citation and full-text levels and risk of bias assessment were performed by two independent reviewers in duplicate, with discrepancies resolved by consensus or third-party adjudication. Bayesian network meta-analyses (NMA) were performed for hearing change and vertigo control outcomes, along with pairwise meta-analyses for these and additional outcomes. RESULTS: We identified 2,889 unique citations, that yielded 23 relevant publications describing 18 unique RCTs (n = 1,231 patients). Overall, risk-of bias appraisal suggested the evidence base to be at unclear or high risk of bias. Amongst pharmacologics, we constructed treatment networks of five intervention groups that included placebo, intratympanic (IT) gentamicin, oral high-dose betahistine, IT steroid and IT steroid plus high-dose betahistine for NMAs of hearing change (improvement or deterioration) and complete vertigo control. IT steroid plus high-dose betahistine was associated with the largest difference in hearing improvement compared to placebo, followed by high-dose betahistine and IT steroid (though 95% credible intervals failed to rule out the possibility of no difference), while IT gentamicin was worse than IT steroid. The NMA of complete vertigo control suggested IT gentamicin was associated with the highest probability of achieving better complete vertigo control compared to placebo, followed by IT steroid plus high-dose betahistine. Only two studies related to surgical interventions were found, and data suggested no statistically significant difference in hearing changes between endolymphatic duct blockage (EDB) versus endolymphatic sac decompression (ESD), and ESD with or without steroid injection. One trial reported that 96.5% of patients in EDB group compared to 37.5% of the patients in ESD group achieved complete vertigo control 24 months after surgery (p = 0.002). CONCLUSION: To achieve both hearing preservation and vertigo control, the best treatment option among the pharmacologic interventions compared may be IT steroid plus high-dose betahistine, considering that IT gentamicin may have good performance to control vertigo but may be detrimental to hearing preservation with high cumulative dosage and short interval between injections. However, IT steroid plus high-dose betahistine has not been compared in head-to-head trials against other interventions except for IT steroid alone in one trial, thus future trials that compare it with other interventions will help establish comparative effectiveness with direct evidence.


Assuntos
Doença de Meniere/tratamento farmacológico , Doença de Meniere/cirurgia , Antibacterianos/uso terapêutico , beta-Histina/uso terapêutico , Gentamicinas/uso terapêutico , Audição/efeitos dos fármacos , Humanos , Esteroides/uso terapêutico , Resultado do Tratamento , Vasodilatadores/uso terapêutico
8.
Drug Discov Ther ; 14(4): 171-176, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908072

RESUMO

The healthcare sector has been overwhelmed by the global rise in the number of COVID-19 cases. The primary care physicians at the forefront of this pandemic are being provided with multiple guidelines (state, national, international). The aim of this review was to examine the existing guidelines for congruence and critically analyze them in light of current evidence. A discordance was noted between the national and state guidelines with respect to indication, duration and dosage of antivirals, steroids/immunomodulators, anticoagulation and convalescent plasma. The lack of concordance between various guidelines mandates the need for a unified national guideline that is regularly updated.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Guias de Prática Clínica como Assunto/normas , Padrões de Prática Médica/normas , Anticoagulantes/uso terapêutico , Antivirais/efeitos adversos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Interações entre Hospedeiro e Microrganismos , Humanos , Imunização Passiva , Fatores Imunológicos/uso terapêutico , Índia/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Esteroides/uso terapêutico
10.
BMC Infect Dis ; 20(1): 708, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993546

RESUMO

BACKGROUND: Intravesical administration of Bacillus Calmette-Guérin (BCG) has proven useful for treatment and prevention of recurrence of superficial bladder cancer and in situ carcinoma. However, fatal side effects such as disseminated infections may occur. Early diagnosis and accurate therapy for interstitial pneumonitis (IP) are important because exacerbation of IP triggered by infections is the major cause of death. Although some fatality reports have suggested newly appeared IP after intravesical BCG treatment, to our knowledge, there are no reports which have demonstrated acute exacerbation of existing IP. Moreover, autopsy is lacking in previous reports. We report the case of a patient with fatal IP exacerbation after BCG instillation and the pathological findings of the autopsy. CASE PRESENTATION: A 77-year-old man with a medical history of IP was referred to our hospital because of fever and malaise. He had received an intravesical injection of BCG 1 day before the admission. His fever reduced after the use of antituberculosis drugs, so he was discharged home. He was referred to our hospital again because of a high fever 7 days after discharge. On hospitalisation, he showed high fever and systemic exanthema. Hepatosplenomegaly and myelosuppression were also observed. Biopsies revealed multiple epithelioid cell granulomas with Langhans giant cells of the liver and bone marrow. Biopsy DNA analyses of Mycobacterium bovis in the bone marrow, sputum, and blood were negative. His oxygen demand worsened drastically, and the ground-glass shadow expanded on the computed tomography scan. He was diagnosed with acute exacerbation of existing IP. We recommenced the antituberculosis drugs with steroid pulse therapy, but he died on day 35 because of respiratory failure. The autopsy revealed a diffuse appearance of multiple epithelioid cell granulomas with Langhans giant cells in multiple organs, although BCG was not evident. CONCLUSIONS: We report the first case of acute exacerbation of chronic IP by BCG infection. This is also the first case of autopsy of a patient with acute exacerbation of existing IP induced by intravesical BCG treatment. Whether the trigger of acute IP exacerbation is infection or hypersensitivity to BCG is still controversial, because pathological evidence confirming BCG infection is lacking. Physicians who administer BCG against bladder cancer should be vigilant for acute exacerbation of IP.


Assuntos
Antituberculosos/uso terapêutico , Vacina BCG/efeitos adversos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/etiologia , Esteroides/uso terapêutico , Exacerbação dos Sintomas , Administração Intravesical , Idoso , Autopsia , Vacina BCG/administração & dosagem , Vacina BCG/uso terapêutico , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/prevenção & controle , Evolução Fatal , Humanos , Doenças Pulmonares Intersticiais/microbiologia , Masculino , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Mycobacterium bovis/genética , Resultados Negativos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Pulsoterapia , Resultado do Tratamento , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/prevenção & controle
11.
Cochrane Database Syst Rev ; 9: CD008333, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32990324

RESUMO

BACKGROUND: Anti-neutrophilic cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) are a group of rare auto-inflammatory diseases that affects mainly small vessels. AAV includes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Anti-cytokine targeted therapy uses biological agents capable of specifically targeting and neutralising cytokine mediators of the inflammatory response. OBJECTIVES: To assess the benefits and harms of anti-cytokine targeted therapy for adults with AAV. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (2019, Issue 7), MEDLINE and Embase up to 16 August 2019. We also examined reference lists of articles, clinical trial registries, websites of regulatory agencies and contacted manufacturers. SELECTION CRITERIA: Randomised controlled trials (RCTs) or controlled clinical trials of targeted anti-cytokine therapy in adults (18 years or older) with AAV compared with placebo, standard therapy or another modality and anti-cytokine therapy of different type or dose. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included four RCTs with a total of 440 participants (mean age 48 to 56 years). We analysed the studies in three groups: 1) mepolizumab (300 mg; three separate injections every four weeks for 52 weeks) versus placebo in participants with relapsing or refractory EGPA; 2) belimumab (10 mg/kg on days 0, 14, 28 and every 28 days thereafter until 12 months after the last participant was randomised) or etanercept (25 mg twice a week) with standard therapy (median 25 months) versus placebo with standard therapy (median 19 months) in participants with GPA/MPA; and 3) infliximab (3 mg/kg on days 1 and 14, before the response assessment on day 42) versus rituximab (0.375g/m2 on days 1, 8, 15 and 22) in participants with refractory GPA for up to 12 months. None of the studies were assessed as low risk of bias in all domains: one study did not report randomisation or blinding methods clearly. Three studies were at high risk and one study was at unclear risk of bias for selective outcome reporting. One trial with 136 participants with relapsing or refractory EGPA compared mepolizumab with placebo during 52 weeks of follow-up and observed one death in the mepolizumab group (1/68, 1.5%) and none in the placebo group (0/68, 0%) (Peto odds ratio (OR) 7.39, 95% confidence interval (CI) 0.15 to 372.38; low-certainty evidence). Low-certainty evidence suggests that more participants in the mepolizumab group had ≥ 24 weeks of accrued remission over 52 weeks compared to placebo (27.9% versus 2.9%; risk ratio (RR) 9.5, 95% CI 2.30 to 39.21), and durable remission within the first 24 weeks sustained until week 52 (19.1% mepolizumab versus 1.5% placebo; RR 13.0, 95% CI 1.75 to 96.63; number needed to treat for an additional beneficial outcome (NNTB) 6, 95% Cl 4 to 13). Mepolizumab probably decreases risk of relapse (55.8% versus 82.4%; RR 0.68, 95% CI 0.53 to 0.86; NNTB 4, 95% CI 3 to 9; moderate-certainty evidence). There was low-certainty evidence regarding similar frequency of adverse events (AEs): total AEs (96.9% versus 94.1%; RR 1.03, 95% CI 0.96 to 1.11), serious AEs (17.7% versus 26.5%; RR 0.67, 95% CI 0.35 to 1.28) and withdrawals due to AEs (2.9% versus 1.5%; RR 2.00, 95% CI 0.19 to 21.54). Disease flares were not measured. Based on two trials with different follow-up periods (mean of 27 months for etanercept study; up to four years for belimumab study) including people with GPA (n = 263) and a small group of participants with MPA (n = 22) analysed together, we found low-certainty evidence suggesting that adding an active drug (etanercept or belimumab) to standard therapy does not increase or reduce mortality (3.4% versus 1.4%; Peto OR 2.45, 95% CI 0.55 to 10.97). Etanercept may have little or no effect on remission (92.3% versus 89.5%; RR 0.97, 95% CI 0.89 to 1.07), durable remission (70% versus 75.3%; RR 0.93, 95% CI 0.77 to 1.11; low-certainty evidence) and disease flares (56% versus 57.1%; RR 0.98, 95% CI 0.76 to 1.27; moderate-certainty evidence). Low-certainty evidence suggests that belimumab does not increase or reduce major relapse (1.9% versus 0%; RR 2.94, 95% CI 0.12 to 70.67) or any AE (92.5% versus 82.7%; RR 1.12, 95% CI 0.97 to 1.29). Low-certainty evidence suggests a similar frequency of serious or severe AEs (47.6% versus 47.6%; RR 1.00, 95% CI 0.80 to 1.27), but more frequent withdrawals due to AEs in the active drug group (11.2%) compared to the placebo group (4.2%), RR 2.66, 95% CI 1.07 to 6.59). One trial involving 17 participants with refractory GPA compared infliximab versus rituximab added to steroids and cytotoxic agents for 12 months. One participant died in each group (Peto OR 0.88, 95% CI, 0.05 to 15.51; 11% versus 12.5%). We have very low-certainty evidence for remission (22% versus 50%, RR 0.44, 95% Cl 0.11 to 1.81) and durable remission (11% versus 50%, RR 0.22, 95% CI 0.03 to 1.60), any severe AE (22.3% versus 12.5%; RR 1.78, 95% CI 0.2 to 16.1) and withdrawals due to AEs (0% versus 0%; RR 2.70, 95% CI 0.13 to 58.24). Disease flare/relapse and the frequency of any AE were not reported. AUTHORS' CONCLUSIONS: We found four studies but concerns about risk of bias and small sample sizes preclude firm conclusions. We found moderate-certainty evidence that in patients with relapsing or refractory EGPA, mepolizumab compared to placebo probably decreases disease relapse and low-certainty evidence that mepolizumab may increase the probability of accruing at least 24 weeks of disease remission. There were similar frequencies of total and serious AEs in both groups, but the study was too small to reliably assess these outcomes. Mepolizumab may result in little to no difference in mortality. However, there were very few events. In participants with GPA (and a small subgroup of participants with MPA), etanercept or belimumab may increase the probability of withdrawal due to AEs and may have little to no impact on serious AEs. Etanercept may have little or no impact on durable remission and probably does not reduce disease flare.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Imunossupressores/administração & dosagem , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/mortalidade , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Síndrome de Churg-Strauss/tratamento farmacológico , Etanercepte/administração & dosagem , Etanercepte/efeitos adversos , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Imunossupressores/efeitos adversos , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Poliangiite Microscópica/tratamento farmacológico , Pessoa de Meia-Idade , Números Necessários para Tratar , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Prevenção Secundária , Esteroides/administração & dosagem
12.
Zhonghua Yi Xue Za Zhi ; 100(35): 2774-2778, 2020 Sep 22.
Artigo em Chinês | MEDLINE | ID: mdl-32972059

RESUMO

Objective: To investigate the effect and mechanism of Polyphyllin Ⅱ on the proliferation, invasion and chemosensitivity of glioma cells. Method: CCK-8 cell proliferation assays and Transwell assays were employed to determine the effect of Polyphyllin Ⅱ on the proliferation and invasion of glioma cells (T98G and LN18), respectively. The expression of E-cadherin, Snail and O6-methylguanine DNA methyltranferase (MGMT) were quantified by Western blot analysis. Results: Polyphyllin Ⅱ could inhibit the proliferation of glioma cells in a time- and does-dependent manner. The half maximal inhibitory concentration (IC(50)) of T98G at 24 h, 48 h and 72 h were (5.82±0.32), (3.57±0.07) and (1.48±0.35) µmol/L, respectively. The IC(50) of LN18 at 24 h, 48 h and 72 h were (6.83±0.11), (4.28±0.29), (2.66±0.22) µmol/L, respectively. After being treated with 2 µmol/L, 4 µmol/L and 6 µmol/L Polyphyllin Ⅱ for 24 h, the percentage of invasive cell area in the chamber area was lower than those in T98G and LN18 control groups (P<0.05). Western blot analysis showed that compared with glioma cells without Polyphyllin Ⅱ treatment, the expression of E-cadherin in T98G and LN18 was higher (F=85.56, P<0.05; F=60.80, P<0.05), but the expression of snail was lower (F=25.34, P<0.05; F=48.28, P<0.05). When temozolomide was used in combination with Polyphyllin Ⅱ at different concentrations, the coefficient of drug interaction (CDI) was less than 1. Western blot showed that MGMT expressions in T98G and LN18 were inhibited compared with glioma cells without Polyphyllin Ⅱ treatment (F=40.38, P<0.05; F=48.44, P<0.05). Conclusion: Polyphyllin Ⅱ can inhibit the proliferation and invasion of glioma cells, and improve its sensitivity to Temozolomide.


Assuntos
Glioma , Temozolomida , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Saponinas , Esteroides
13.
Pediatrics ; 146(3)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32868471

RESUMO

BACKGROUND: Legal performance-enhancing substance(s) (PES) (eg, creatine) are widely used among adolescent boys and young men; however, little is known about their temporal associations with substance use behaviors. METHODS: We analyzed prospective cohort data from the National Longitudinal Study of Adolescent to Adult Health, Waves I to IV (1994-2008). Logistic regressions were used to first assess adolescent substance use (Wave I) and use of legal PES (Wave III) and second to assess use of legal PES (Wave III) and subsequent substance use-associated risk behaviors (Wave IV), adjusting for potential confounders. RESULTS: Among the sample of 12 133 young adults aged 18 to 26 years, 16.1% of young men and 1.2% of young women reported using legal PES in the past year. Adolescent alcohol use was prospectively associated with legal PES use in young men (odds ratio 1.39; 95% confidence interval [CI] 1.13-1.70). Among young men, legal PES use was prospectively associated with higher odds of problematic alcohol use and drinking-related risk behaviors, including binge drinking (adjusted odds ratio [aOR] 1.35; 95% CI 1.07-1.71), injurious and risky behaviors (aOR 1.78; 95% CI 1.43-2.21), legal problems (aOR 1.52; 95% CI 1.08-2.13), cutting down on activities and socialization (aOR 1.91; 95% CI 1.36-2.78), and emotional or physical health problems (aOR 1.44; 95% CI 1.04-1.99). Among young women, legal PES use was prospectively associated with higher odds of emotional or physical health problems (aOR 3.00; 95% CI 1.20-7.44). CONCLUSIONS: Use of legal PES should be considered a gateway to future problematic alcohol use and drinking-related risk behaviors, particularly among young men.


Assuntos
Substâncias para Melhoria do Desempenho/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/etiologia , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Intoxicação Alcoólica/complicações , Aminoácidos/efeitos adversos , Atletas/estatística & dados numéricos , Índice de Massa Corporal , Intervalos de Confiança , Creatina/efeitos adversos , Desidroepiandrosterona/efeitos adversos , Feminino , Humanos , Modelos Logísticos , Masculino , Fumar Maconha/efeitos adversos , Razão de Chances , Estudos Prospectivos , Assunção de Riscos , Fatores Sexuais , Fumar/efeitos adversos , Esteroides/efeitos adversos , Consumo de Álcool por Menores , Adulto Jovem
14.
Rev. esp. patol ; 53(3): 182-187, jul.-sept. 2020. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-192407

RESUMO

We describe the implementation of a COVID-19 Autopsy Programme in our Hospital, report the main findings from the first autopsy of the programme and briefly review the reports of lung pathology of these patients


En este artículo presentamos el proceso de implementación de un Programa de Autopsias COVID-19 en nuestro hospital, presentamos los principales hallagos de la primera autopsia realizada y revisamos brevemente la patología pulmonar publicada previamente en estos pacientes


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/complicações , Autopsia/estatística & dados numéricos , Causas de Morte , Infecções por Coronavirus/patologia , Alvéolos Pulmonares/patologia , Síndrome Respiratória Aguda Grave/complicações , Vírus da SARS/isolamento & purificação , Apneia Obstrutiva do Sono/complicações , Hipertensão/complicações , Reação em Cadeia da Polimerase/métodos , Esteroides/uso terapêutico , Pandemias , Técnicas Histológicas/métodos , Espanha/epidemiologia
15.
Nature ; 584(7819): 75-81, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760044

RESUMO

Chemical reactions that reliably join two molecular fragments together (cross-couplings) are essential to the discovery and manufacture of pharmaceuticals and agrochemicals1,2. The introduction of amines onto functionalized aromatics at specific and pre-determined positions (ortho versus meta versus para) is currently achievable only in transition-metal-catalysed processes and requires halogen- or boron-containing substrates3-6. The introduction of these groups around the aromatic unit is dictated by the intrinsic reactivity profile of the method (electrophilic halogenation or C-H borylation) so selective targeting of all positions is often not possible. Here we report a non-canonical cross-coupling approach for the construction of anilines, exploiting saturated cyclohexanones as aryl electrophile surrogates. Condensation between amines and carbonyls, a process that frequently occurs in nature and is often used by (bio-)organic chemists7, enables a predetermined and site-selective carbon-nitrogen (C-N) bond formation, while a photoredox- and cobalt-based catalytic system progressively desaturates the cyclohexene ring en route to the aniline. Given that functionalized cyclohexanones are readily accessible with complete regiocontrol using the well established carbonyl reactivity, this approach bypasses some of the frequent selectivity issues of aromatic chemistry. We demonstrate the utility of this C-N coupling protocol by preparing commercial medicines and by the late-stage amination-aromatization of natural products, steroids and terpene feedstocks.


Assuntos
Compostos de Anilina/síntese química , Hidrogênio/química , Processos Fotoquímicos , Aminação , Aminas/química , Compostos de Anilina/química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Catálise/efeitos da radiação , Cicloexanonas/química , Oxirredução/efeitos da radiação , Processos Fotoquímicos/efeitos da radiação , Esteroides/síntese química , Esteroides/química , Terpenos/síntese química , Terpenos/química
16.
Medicine (Baltimore) ; 99(34): e21936, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846862

RESUMO

RATIONALE: IgG4-related disease (IgG4-RD) is a systemic disease that can involve various organs and is characterized by the infiltrations of IgG4-positive plasma cells and lymphocytes, fibrosis, and elevated serum IgG4 levels. IgG4-related sclerosing cholangitis (IgG4-RSC) is a subtype of IgG4-RD. No certain relationship between IgG4-RSC and cholangiocarcinoma has been established as yet, and there have been few reports of the simultaneous diagnosis of IgG4-RSC and cholangiocarcinoma. PATIENT CONCERNS: A 76-year-old male visited our gastroenterology department due to the recent occurrence of pruritus and jaundice. DIAGNOSIS: Computed tomography (CT) scan showed ductal wall swelling and enhancement from both intrahepatic duct confluence to the common bile duct, upper biliary dilatation, and accompanying autoimmune pancreatitis (a sub type of IgG4-RD). Biopsy of the distal common bile duct by endoscopic retrograde cholangiopancreatography (ERCP) resulted in a diagnosis of IgG4-RSC. Subsequently, adenocarcinoma was identified by repeated cytology of bile juice. Finally, Klatskin tumor type IIIA and IgG4-RSC were concurrently diagnosed. INTERVENTIONS: IgG4-RSC was treated with steroid and Klatskin tumors by gemcitabine + cisplatin chemotherapy. OUTCOMES: The jaundice had improved and CT showed substantial improvement of the intrahepatic duct dilatation. LESSONS: IgG4-RSC and cholangiocarcinoma are easily confused, but their treatments are quite different, and thus, care must be taken during diagnosis. Furthermore, these 2 diseases may co-exist. Therefore, even if IgG4-RSC is diagnosed first, the possibility of accompanying cholangiocarcinoma should be thoroughly investigated.


Assuntos
Colangiocarcinoma/complicações , Colangite Esclerosante/patologia , Imunoglobulina G/imunologia , Tumor de Klatskin/complicações , Tumor de Klatskin/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Colangiocarcinoma/patologia , Colangiopancreatografia Retrógrada Endoscópica , Colangite Esclerosante/diagnóstico por imagem , Colangite Esclerosante/tratamento farmacológico , Cisplatino/uso terapêutico , Ducto Colédoco/patologia , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Diagnóstico Diferencial , Humanos , Doença Relacionada a Imunoglobulina G4/patologia , Icterícia/diagnóstico , Icterícia/etiologia , Tumor de Klatskin/classificação , Tumor de Klatskin/tratamento farmacológico , Masculino , Prurido/diagnóstico , Prurido/etiologia , Esteroides/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
17.
Medicine (Baltimore) ; 99(30): e21283, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791709

RESUMO

BACKGROUND: Previous systemic reviews have examined the efficacy of individual therapeutic agents, but which type of treatment is superior to another has not been pooled or analyzed. The objective of the current study was to compare the clinical effectiveness of epidural steroid injection (ESI) versus conservative treatment for patients with lumbosacral radicular pain. METHODS: A systematic search was conducted with MEDLINE, EMBASE, and CENTRAL databases with a double-extraction technique for relevant studies published between 2000 and January 10, 2019. The randomized controlled trials which directly compared the efficacy of ESI with conservative treatment in patients with lumbosacral radicular pain were included. Outcomes included visual analog scale, numeric rating scale, Oswetry disability index, or successful events. Two reviewers extracted data and evaluated the methodological quality of papers using the Cochrane Collaboration Handbook. A meta-analysis was performed using Revman 5.2 software. The heterogeneity of the meta-analysis was also assessed. RESULTS: Of 1071 titles initially identified, 6 randomized controlled trials (249 patients with ESI and 241 patients with conservative treatment) were identified and included in this meta-analysis. The outcome of the pooled analysis showed that ESI was beneficial for pain relief at short-term and intermediate-term follow-up when compared with conservative treatment, but this effect was not maintained at long-term follow-up. Successful event rates were significantly higher in patients who received ESI than in patients who received conservative treatment. There were no statistically significant differences in functional improvement after ESI and conservative treatment at short-term and intermediate-term follow-up. The limitations of this meta-analysis resulted from the variation in types of interventions and small sample size. CONCLUSIONS: According to the results of this meta-analysis, the use of ESI is more effective for alleviating lumbosacral radicular pain than conservative treatments in terms of short-term and intermediate-term. Patients also reported more successful outcomes after receiving ESI when compared to conservative treatment. However, this effect was not maintained at long-term follow-up. This meta-analysis will help guide clinicians in making decisions for the treatment of patients with lumbosacral radicular pain, including the use of ESI, particularly in the management of pain at short-term.


Assuntos
Injeções Epidurais/métodos , Dor Lombar/tratamento farmacológico , Radiculopatia/tratamento farmacológico , Humanos , Região Lombossacral/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Esteroides/administração & dosagem
18.
Life Sci ; 258: 118192, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32781062

RESUMO

The present study was conducted to identify possible health - promoting effects of wogonin (Wog) on testicular dysfunction in rats caused by cadmium. Pre-treatment of cadmium chloride (Cd: 5 mg/kg b.wt.) administered rats with wogonin (10 mg/kg b.wt) resulted in significant improvement in Cd-induced decrease in body and organ (testes and epididymides) weights. Wogonin treatment significantly improved Cd-induced reduction in sperm quality and quantity, steroidogenic gene (SFI, StAR, CYP11A1, 3ß-HSD, CYP17A1 and 17ß-HSD) and protein (SF1, StAR and CYP17A1) expressions and serum testosterone levels. Wogonin treatment provided significant protection to Cd-induced aggression in testicular oxidative (elevated levels of MDA) and anti-oxidative (diminished activities of SOD, CAT and GPx) status. Wog significantly up-regulated mRNA levels of Nrf2, NQO1 and HO-1 and down-regulation of Keap1 in cadmium treated testes. Wogonin administration significantly suppressed Cd-stimulated increase in inflammatory reactions (increase in NF-κB p65 DNA, p-IKKß, TNF-α levels and decrease in IL-10 levels). Wogonin prevented apoptotic damage by enhanced protein distribution of caspase-9, caspase-3, and Bax due to Cd exposure. Furthermore, Wogonin presented significant protection to histo-morphometric changes resulted after Cd administration. Taken together, the findings of this study provided clear evidence of the therapeutic potential of Cd-induced testicular toxicity at least partly due to its antioxidant, anti-inflammatory and anti-apoptotic properties.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Cádmio/toxicidade , Flavanonas/farmacologia , Substâncias Protetoras/farmacologia , Transdução de Sinais , Testículo/patologia , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Epididimo/efeitos dos fármacos , Epididimo/patologia , Comportamento Alimentar/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônios/sangue , Inflamação/patologia , Masculino , Oxirredução , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Esteroides/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo
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