Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 13.841
Filtrar
1.
Medicine (Baltimore) ; 98(41): e17565, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593140

RESUMO

RATIONALE: Invasive moles occur in the fertile period, with about 95% occurring after previous mole removal and the remaining 5% occurring after several other pregnancies. PATIENT CONCERNS: A 27-year-old patient developed a rare invasive mole two months after a missed abortion. DIAGNOSES: A transvaginal ultrasound scan revealed a 3.6 × 2.9 × 2.4 cm sized lesion with cystic vascular areas within it, within the myometrium of the right fundal posterior region of the uterus. There was no metastasis to other organs. INTERVENTIONS: After administration of methotrexate, the level of beta-human chorionic gonadotropin (ß-hCG) was elevated and liver enzymes were also markedly elevated. She wanted to retain fertility for future pregnancies. After laparoscopic removal of the myometrial invasive mole, the incision site was sutured with a 3-0 V-Loc. OUTCOMES: One year later, a natural pregnancy occurred and a cesarean section was performed at 36 weeks. LESSONS: This is the first reported case of its type. Our case demonstrated that pelviscopic removal of an invasive mole is possible if there are no other metastases, and that future pregnancy and childbirth are still feasible in women of reproductive age.


Assuntos
Mola Hidatiforme Invasiva/cirurgia , Miométrio/cirurgia , Pelve/diagnóstico por imagem , Neoplasias Uterinas/cirurgia , Adulto , Gonadotropina Coriônica/análise , Feminino , Humanos , Mola Hidatiforme Invasiva/diagnóstico por imagem , Mola Hidatiforme Invasiva/patologia , Laparoscopia/métodos , Metotrexato/administração & dosagem , Miométrio/patologia , Gravidez , Resultado do Tratamento , Ultrassonografia/métodos , Neoplasias Uterinas/patologia
2.
Internist (Berl) ; 60(10): 1059-1073, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31471629

RESUMO

Large-vessel vasculitis includes giant cell arteritis (GCA) and Takayasu arteritis (TA). GCA can affect persons from the age of 50 years and is more frequent among women. The disease course generally begins with an acute phase, with patients feeling very unwell and experiencing temporal headaches. Rapid diagnosis and treatment are necessary to reduce the risk of blindness. A suspected diagnosis must be confirmed by imaging, histology is optional. Initial treatment comprises oral prednisone. Recent studies have demonstrated inhibition of interleukin­6 with tocilizumab (TCZ) to be highly effective. Alternatively, methotrexate can be administered in a steroid-sparing approach. In contrast, TA onset is generally during childhood or adolescence, and begins with moderate systemic inflammation. The aorta and its main branches are affected. Treatment comprises steroids, disease-modifying antirheumatic drugs, and the tumor necrosis factor inhibitor infliximab or TCZ.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antirreumáticos/administração & dosagem , Arterite de Células Gigantes/tratamento farmacológico , Imunossupressores/administração & dosagem , Arterite de Takayasu/tratamento farmacológico , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Feminino , Células Gigantes , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Resultado do Tratamento
3.
Expert Opin Drug Saf ; 18(11): 1009-1015, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31478396

RESUMO

Introduction: Therapeutic drug monitoring in oncology is used to prevent major toxicities of selected anticancer agents due to overexposure by individualizing the dose based on a pharmacokinetic target. Areas covered: Numerous studies relating a relation between pharmacokinetic variability and toxicity have been reported since the eighties but very few have been implemented in clinical practice due to a lack of validation and harmonization, logistical constraints and reluctance from oncologists. Following recent recommendations, this paper highlights the current-validated applications of pharmacokinetic monitoring in oncology focusing on the safety of anticancer therapies. Expert opinion: Paradoxically given the oldness of the agents, guidelines of dose adjustment have been recently available for intravenous busulfan, 5-fluorouracil, and high-dose methotrexate. Interestingly, besides the enhancement of tolerability, it applies to potential curative clinical situations. In an era of personalized oncology that integrates complex molecular factors in the treatment of cancer, education is needed for oncologists to show the benefits of this valuable (even old) resource for the safety of patients. Therapeutic drug monitoring for busulfan, 5-fluorouracil and methotrexate will still hold in the future unless more active agents are available in the concerned indications.


Assuntos
Antineoplásicos/administração & dosagem , Monitoramento de Medicamentos/métodos , Neoplasias/tratamento farmacológico , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Bussulfano/farmacocinética , Relação Dose-Resposta a Droga , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/farmacocinética , Humanos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Metotrexato/farmacocinética , Guias de Prática Clínica como Assunto , Medicina de Precisão/métodos
4.
JAMA ; 322(10): 936-945, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503307

RESUMO

Importance: Methotrexate and mycophenolate mofetil are commonly used immunomodulatory therapies for achieving corticosteroid-sparing control of noninfectious uveitis, but there is uncertainty about which drug is more effective. Objective: To compare the effect of methotrexate and mycophenolate for achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis. Design, Setting, and Participants: The First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial screened 265 adults with noninfectious uveitis requiring corticosteroid-sparing immunosuppressive therapy from 9 referral eye centers in India, the United States, Australia, Saudi Arabia, and Mexico between August 22, 2013, and August 16, 2017. Follow-up ended on August 20, 2018. Interventions: Patients were randomized to receive oral methotrexate, 25 mg weekly (n = 107), or oral mycophenolate mofetil, 3 g daily (n = 109). Main Outcomes and Measures: The primary outcome was treatment success at 6 months, which was defined as having control of inflammation in both eyes, no more than 7.5 mg prednisone daily and less than or equal to 2 drops of prednisolone acetate 1%, and no treatment failure due to safety or intolerability. Patients underwent follow-up to 12 months while receiving the same treatment or switched to the other antimetabolite, depending on their 6-month outcome. Results: Among 216 patients who were randomized (median age, 38 years; 135 (62.5%) women), 194 (89.8%) completed follow-up through 6 months. Treatment success occurred in 64 (66.7%) patients in the methotrexate group vs 56 (57.1%) in the mycophenolate group (difference, 9.5% [95% CI, -5.3% to 21.8%]; odds ratio [OR], 1.50 [95% CI, 0.81 to 2.81]; P = .20). Among patients with posterior uveitis or panuveitis, treatment success was achieved in 58 (74.4%) in the methotrexate group vs 42 (55.3%) in the mycophenolate group (difference, 19.1% [95% CI, 3.6% to 30.6%]; OR, 2.35 [95% CI, 1.16 to 4.90]; P = .02); whereas among patients with intermediate uveitis treatment success occurred in 6 (33.3%) in the methotrexate group vs 14 (63.6%) in the mycophenolate group (difference, -30.3% [95% CI, -51.6% to 1.1%]; OR, 0.29 [95% CI, 0.08 to 1.05]; P = .07; P for interaction = .004). Elevated liver enzymes were the most common nonserious laboratory adverse event, occurring in 14 patients (13.0%) in the methotrexate group and 8 patients (7.4%) in the mycophenolate group. Conclusions and Relevance: Among adults with noninfectious uveitis, the use of mycophenolate mofetil compared with methotrexate as first-line corticosteroid-sparing treatment did not result in superior control of inflammation. Further research is needed to determine if either drug is more effective based on the anatomical subtype of uveitis. Trial Registration: ClinicalTrials.gov Identifier: NCT01829295.


Assuntos
Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Uveíte/tratamento farmacológico , Adulto , Anti-Inflamatórios/administração & dosagem , Quimioterapia Combinada , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Testes de Função Hepática , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Prednisolona/administração & dosagem
5.
Medicine (Baltimore) ; 98(35): e16895, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464920

RESUMO

RATIONALE: Methotrexate (MTX) is an antimetabolite of folic acid, which is used for management of ectopic pregnancy. MTX-related toxicity may include cutaneous mucosal damage, bone marrow suppression, gastrointestinal disorders (gastritis, diarrhea, hematitis), liver and kidney function damage, pulmonary toxicity, cardiac toxicity, and nerve toxicity. However, it is not usual for vulvar edema induced by low-dose methotrexate. PATIENT CONCERNS: In this case report, we described a patient with severe vulvar edema and oral cavity ulceration and scalp ulceration induced by low-dose MTX treatment for ectopic pregnancy. Her presenting complaints were pain in the vulva, oral cavity, and scalp. DIAGNOSES: The patient was diagnosed based on clinical findings for MTX toxic reactions. INTERVENTIONS: Vulva was disinfectioned with iodide and Kangfuxin solution, her mouth was rinsed with mouthwash. Three compound glycyrrhizin tablets were orally administered (3 times/day). After 10 days, the broken skin and mucous membrane healed. OUTCOMES: The vulvar edema and oral cavity ulceration and scalp ulceration healed. LESSONS: Our study demonstrated that even low-dose MTX can be induced skin and mucosal injury, patients and doctors should timely detection of drug toxicity reactions, immediately rescue, prompt discontinuation of medication, and symptomatic treatment to avoid accidental occurrence.


Assuntos
Metotrexato/administração & dosagem , Metronidazol/administração & dosagem , Gravidez Ectópica/tratamento farmacológico , Vaginite por Trichomonas/tratamento farmacológico , Doenças da Vulva/induzido quimicamente , Dor Abdominal/etiologia , Administração Oral , Adulto , China , Feminino , Ácido Glicirrízico/administração & dosagem , Ácido Glicirrízico/uso terapêutico , Humanos , Injeções Intramusculares , Materia Medica/administração & dosagem , Materia Medica/uso terapêutico , Metotrexato/efeitos adversos , Metronidazol/uso terapêutico , Gravidez , Gravidez Ectópica/diagnóstico , Resultado do Tratamento , Hemorragia Uterina/etiologia , Doenças da Vulva/tratamento farmacológico
6.
Adv Clin Exp Med ; 28(9): 1229-1235, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31464109

RESUMO

BACKGROUND: Subcutaneous methotrexate (sMTX) administration is considered more effective than the oral route due to better bioavailability and a lower rate of adverse drug reactions (ADRs); however, clinical data supporting this hypothesis is scarce. OBJECTIVES: The aim of the study was to evaluate the efficacy and tolerability of sMTX in patients with active rheumatoid arthritis (RA), including a subset classified as an early stage of RA. MATERIAL AND METHODS: A post-marketing, multicenter, open-label, non-randomized, non-interventional study enrolled 771 adult patients with active RA treated with sMTX (Metex®) for 2-6 weeks. The evaluation of therapy effectiveness (DAS28-ESR or DAS28-CRP) and monitoring of ADRs was an element of routine patient management. Therapy effectiveness was scored as the achievement of remission or response (according to European League Against Rheumatism (EULAR)). RESULTS: Among 761 (98.7%) patients that continued sMTX (after 25-31 weeks), clinical response was achieved by 69.5%, remission by 19.2% and low disease activity by 34.2%. Patients aged >60 years were less likely to achieve both remission (odds ratio (OR) = 0.61 (95% confidence interval (95% CI) = 0.39-0.93)) and clinical response (OR = 0.82 (95% CI = 0.71-0.95)), while overweight/obese patients (OR = 1.11 (95% CI = 1.00-1.24)) and those with early RA had greater chance to reach a clinical response (OR = 1.18 (95% CI = 1.03-1.34)). There were 16 ADRs (no serious or severe). In addition, at least 2-fold increase in alanine transaminase (ALT) activity was noted in 10 patients (1.3%). CONCLUSIONS: After 6-month therapy with sMTX, about 70% of patients with RA achieve a clinical response, and remission was observed in 20%. Younger age, overweight/obesity and an early stage of the disease are factors increasing therapy effectiveness; sMTX is well tolerated.


Assuntos
Antirreumáticos , Artrite Reumatoide , Metotrexato/uso terapêutico , Administração Cutânea , Adulto , Idoso , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Sobrepeso , Vigilância de Produtos Comercializados , Resultado do Tratamento
7.
Medicine (Baltimore) ; 98(32): e16682, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393368

RESUMO

Some patients have poor response to adult-onset Still disease (AOSD) traditional treatment, which easily recurs during the reduction of prednisone. We observed the efficacy and safety of tocilizumab combined with methotrexate (MTX) in the treatment of refractory AOSD, and to explore the possibility of reducing the dosage of tocilizumab after disease control.A total of 28 refractory AOSD cases who had an inadequate response to corticosteroids combined with at least 1 traditional immunosuppressive agent, and even large-dose prednisone could not relieve their conditions after recurrence, were selected in this study. They were treated with tocilizumab (intravenous 8 mg/kg) combined with MTX (oral 12.5 mg once a week). In detail, tocilizumab was firstly given every 4 weeks and after 6-month remission, it was then given every 8 weeks. Some items including body temperature, skin rash, joint swelling and pain, hepatosplenomegaly, blood routine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum ferritin, and dosage of prednisone were observed before treatment as well as 2, 4, 8, 12, 24, 36, and 48 weeks after treatment. The adverse reactions occurring during the treatment were recorded.The body temperature was normal, the skin rash as well as joint swelling and pain disappeared, and laboratory indexes including CRP, ESR, white blood cell, neutrophilic granulocyte, platelet, hemoglobin, and ferritin were significantly improved after 8-week treatment (all P < .05). The clinical symptoms and laboratory indexes above mentioned were continuously improved 12, 24, 36, and 48 weeks after treatment. The mean dosage of prednisone was reduced from 71.4 ±â€Š20.7 mg/day to 55.0 ±â€Š11.1 mg/day after 2-week treatment, and to 3.3 ±â€Š2.1 mg/day after 48-week treatment (all P < .05). Prednisone was discontinued in 5 cases after 36-week treatment and in 7 cases after 48-week treatment. No serious adverse reactions occurred during the treatment.Tocilizumab can rapidly and markedly improve the clinical symptoms and laboratory indexes and contribute to reduction and discontinuation of prednisone in refractory AOSD. The patients' conditions are stable after reduction or discontinuation of prednisone and the tocilizumab possesses good safety.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antirreumáticos/administração & dosagem , Metotrexato/administração & dosagem , Doença de Still de Início Tardio/tratamento farmacológico , Administração Intravenosa , Administração Oral , Adulto , Anticorpos Monoclonais Humanizados/farmacologia , Antirreumáticos/farmacologia , Quimioterapia Combinada , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Masculino , Metotrexato/farmacologia , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Resultado do Tratamento
8.
Life Sci ; 233: 116750, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31408659

RESUMO

AIM: Rheumatoid arthritis (RA) is the most widespread inflammatory arthropathy, which causes severe disability. It is highly important to ameliorate the side effects caused by different drugs used to treat RA. Therefore, this study assessed the potential role of ß-caryophyllene (BCP) in treating adjuvant-induced arthritis (AIA), increasing the efficacy of methotrexate (MTX) and/or leflunomide (LEF), and ameliorating their side effects. MATERIAL AND METHODS: AIA was induced in rats by injecting complete Freund's adjuvant. The rats were divided into different groups such as sham group; control group; monotherapy groups, including BCP (300 mg/kg), MTX (1 mg/kg), and LEF (10 mg/kg); and combined groups, including MTX + BCP, LEF + BCP, MTX + LEF, and MTX + LEF + BCP groups. KEY FINDINGS: Monotherapy with BCP or MTX or LEF as well as MTX + LEF significantly reduced paw thickness and arthritic index; the histopathological changes in hind paw joints were recovered; and oxidative stress and tumor necrosis factor-alpha (TNF-α) levels in arthritic rats were reduced. The co-administration of BCP and MTX and/or LEF significantly improved the therapeutic efficacy of MTX and/or LEF and significantly reduced the myelosuppressive and hepatotoxic effects of MTX and/or LEF. Taken together, BCP could be used with MTX and/or LEF for the treatment of RA to reduce the side effects of the drugs and increase their efficacy.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Artrite Experimental/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Imunossupressores/administração & dosagem , Leflunomida/administração & dosagem , Metotrexato/administração & dosagem , Sesquiterpenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antimetabólitos Antineoplásicos/efeitos adversos , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Quimioterapia Combinada , Imunossupressores/efeitos adversos , Leflunomida/efeitos adversos , Masculino , Metotrexato/efeitos adversos , Ratos , Ratos Wistar , Sesquiterpenos/administração & dosagem
9.
Pan Afr Med J ; 32: 158, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31303928

RESUMO

Renal amyloidosis is a rare complication of adult onset Still's disease. We here report three cases of renal amyloidosis in a series of 33 cases of adult onset Still's disease. The three patients enrolled had an average age of 43 years (with a range from 33 to 58 years). The diagnosis of Still's disease was retained on the basis of febrile polyarthritis (3 cases) associated with fleeting rush (1 case), biologic inflammatory syndrome in the absence of any infectious, inflammatory or neoplastic causes. All patients were treated with corticosteroids secondarily associated with methotrexate due to destructive polyarthritis (2 cases) and to a recurrence (1 case). Renal amyloidosis had occurred 4.9 years after Still's disease (with a range from 33 months to 7 years). Amyloidosis was revealed by nephrotic syndrome (3 cases) associated with renal failure (1 case). Diagnosis was based on renal puncture biopsy (3 cases) which showed AA amyloidosis (2 cases) and untyped amyloidosis (1 case). All patients received colchicine. Outcome was favorable in a female patient while in the other two patients the disease progressed to chronic renal failure. Renal amyloidosis uncommonly results from adult onset Still's disease. Once the disease gets established it can be life-threatening.


Assuntos
Amiloidose/etiologia , Síndrome Nefrótica/etiologia , Doença de Still de Início Tardio/complicações , Corticosteroides/administração & dosagem , Adulto , Amiloidose/diagnóstico , Amiloidose/tratamento farmacológico , Biópsia por Agulha , Colchicina/administração & dosagem , Progressão da Doença , Feminino , Humanos , Falência Renal Crônica/etiologia , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Insuficiência Renal/etiologia , Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/tratamento farmacológico
10.
Int J Nanomedicine ; 14: 4949-4960, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308665

RESUMO

Purpose: The objective of this study was to exploit a novel methotrexate (MTX)-loaded solid self-microemulsifying drug delivery system (SMEDDS) with enhanced bioavailability and photostability. Materials and methods: The optimized liquid SMEDDS was composed of castor oil, Tween® 80, and Plurol® diisostearique at a voluminous ratio of 27:63:10. The solid SMEDDS was formulated by spray drying liquid SMEDDS with the solid carrier (calcium silicate). Particle size analyzer, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy experiments characterized the physiochemical properties of the MTX-loaded solid SMEDDS. These properties include a z-average diameter of emulsion around 127 nm and the amorphous form of the solid SMEDDS. Furthermore, their solubility, dissolution, and pharmacokinetics in Sprague-Dawley rats were analyzed in comparison with the MTX powder. Results: The final dissolution rate and required time for complete release of solid SMEDDS were 1.9-fold higher and 10 min shorter, respectively, than those of MTX powder. Pharmacokinetic analysis demonstrated 2.04- and 3.41-fold increments in AUC and Cmax, respectively in comparison to MTX powder. The AUC and Cmax were significantly increased in solid SMEDDS. Finally, the photostability studies revealed the substantially enhanced photostability of the MTX-loaded SMEDDS under the forced degradation and confirmatory conditions. Conclusion: This solid SMEDDS formulation could be an outstanding candidate for improving the oral bioavailability and photostability of MTX.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Emulsões/química , Luz , Metotrexato/administração & dosagem , Metotrexato/farmacologia , Administração Oral , Animais , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Metotrexato/sangue , Metotrexato/farmacocinética , Petróleo , Transição de Fase , Ratos Sprague-Dawley , Solubilidade , Difração de Raios X
11.
Autoimmun Rev ; 18(9): 102359, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31323362

RESUMO

OBJECTIVE: The aim of this study is to compare the frequency of remission, according to DORIS definitions, of inception patients from two European SLE cohorts, with a special focus on the differences between the therapeutic schemes of both Units. METHODS: Inception patients enrolled after 2000 from the longitudinal Cruces Lupus Cohort (CC) and Bordeaux Lupus Cohort (BC) were included. The main endpoint was the achievement of clinical remission on treatment (ClinROnT). ClinROnT was assessed yearly from the 1st until the 5th year following the diagnosis of SLE. RESULTS: 173 patients, 92 CC and 81 BC, were studied. The clinical presentation of both cohorts was similar, with no significant differences in the mean SLEDAI score at diagnosis (6.6 vs. 8.1, p = 0.06). Patients from CC were treated more frequently with hydroxychloroquine (mean 57 vs. 43 months), methotrexate (24% vs. 11%) and pulse methyl-prednisolone (42% vs. 26%), and received lower doses of oral prednisone (average dose during the follow up 2.3 vs. 7.2 mg/d, p < 0.001). Patients in CC were more likely to achieve ClinROnT at year one, 84% vs. 43% (p < 0.001). Prolonged ClinROnT during the 5 years of follow up was more frequent in CC: 70% vs. 28%, p < 0.001. Patients in CC were also more likely to achieve ClinROnT after controlling for baseline SLEDAI (adjusted HR 1.69, 95%CI 1.21-2.35) and for the presenting clinical manifestations (adjusted HR 1.72, 95% CI 1.2-2.4). CONCLUSION: Prolonged ClinROnT was achievable by using a therapeutic regime consisting of lower doses of oral prednisone and maximizing the use of hydroxychloroquine, pulse methyl-prednisolone and methotrexate.


Assuntos
Imunossupressores/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Prednisona/administração & dosagem , Administração Oral , Adulto , Estudos de Coortes , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , França/epidemiologia , Glucocorticoides/administração & dosagem , Humanos , Hidroxicloroquina/administração & dosagem , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Metotrexato/administração & dosagem , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Indução de Remissão , Espanha/epidemiologia , Resultado do Tratamento , Adulto Jovem
12.
Crit Rev Oncol Hematol ; 141: 139-145, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31295667

RESUMO

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of diffuse large B-cell lymphoma. The frontline treatment with high-dose methotrexate based immunochemotherapy is not curative for the majority of patients. Gene expression profiling and next-generation sequencing have recently provided plethora of data shedding light on pathogenic mechanisms sustain PCNSL and identifying potential vulnerable mechanisms to be explored therapeutically. Here, we review established molecular drivers of PCNSL and targeted drugs that may change the current therapeutic paradigm.


Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Terapia de Alvo Molecular , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Terapias em Estudo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunoterapia/métodos , Imunoterapia/tendências , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Metotrexato/administração & dosagem , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Terapias em Estudo/métodos , Terapias em Estudo/tendências
13.
J Cancer Res Clin Oncol ; 145(8): 1987-1998, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31214760

RESUMO

PURPOSE: Based on the poor prognosis of drug resistance in pediatric acute lymphoblastic leukemia (ALL) and adverse effects of chemotherapy, this study was aimed to evaluate the effect of several herbal extracts on leukemic cells. METHODS: Two subtypes of T- and B-ALL cell lines, followed by ALL primary cells were treated with cinnamon, ginger, and green tea extracts, alone or in combination with methotrexate (MTX). Possible apoptosis was investigated using Annexin-V/PI double staining. Real-time PCR was applied to evaluate the expression levels of related ABC transporters upon combination therapy. RESULTS: The IC50s for cinnamon, ginger and green tea extracts on ALL cell lines were 300 µg/ml, 167 µg/ml and 70 µg/ml, respectively. Surprisingly, the methotrexate (MTX)-resistant sub-line showed more sensitivity to ginger. Combined treatment with ginger and MTX showed synergistic effects on CCRF-CEM, Nalm-6 and ALL primary cells. It was shown that ginger does not impair the high expression levels of ABCA2 or ABCA3 transporter genes in the ALL malignant cells, suggesting other molecular pathways involved in its anticancer potential. CONCLUSION: To the best of our knowledge, this is the first study that reveals the antileukemic effect of ginger extract on both, pediatric ALL cell lines and primary cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Gengibre/química , Extratos Vegetais/farmacologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pré-Escolar , Cinnamomum zeylanicum/química , Terapia Combinada , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Fitoterapia , Extratos Vegetais/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Chá/química , Células Tumorais Cultivadas , Adulto Jovem
14.
Pharm Res ; 36(8): 123, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31218557

RESUMO

PURPOSE: This investigation was aimed to explore the targeting potential of folate conjugated double liposomes (fDLs) bearing combination of synergistic drugs (Prednisolone and Methotrexate) for effective management of the rheumatoid arthritis (RA). METHODS: To overcome the drawbacks of monotherapy, a combination of prednisolone (PRD) (an anti-inflammatory agent) and methotrexate (MTX) (a disease modifying anti-rheumatoid agent, DMARDs) was chosen for dual targeting approach. fDLs were prepared in two steps i.e. development of inner liposomes (ILs) using thin film casting method followed by encapsulation of ILs within folate conjugated outer liposomes (double liposomes; fDLs). Developed liposomes were characterized for various physicochemical parameters and in vivo performance. RESULTS: fDLs were prepared using FA-PEG-4000-NH-DSPE conjugate. These double liposomes were having 429.3 ± 3.6 nm in size with 0.109 PDI, 8.01 ± 0.3 mV zeta potential (ζ) and 66.7 ± 3.9% and 45.3 ± 1.7% entrapments of PRD and MTX, respectively. After 24 h, the concentrations of PRD in blood were observed to be 8.66 ± 3.11 (ILs) and 15.13 ± 0.81% (DLs) while concentration of MTX were found to be 10.89 ± 0.69 and 2.34 ± 3.15% when given as ILs and fDLs, respectively. The concentration of both drugs in inflamed joint was observed to be higher than that in the non-inflamed joints. CONCLUSIONS: The folate conjugated double liposomes possess superior targeting efficiency than conjugated and unconjugated single liposomes.


Assuntos
Anti-Inflamatórios/farmacocinética , Antirreumáticos/farmacocinética , Artrite Reumatoide/tratamento farmacológico , Ácido Fólico/química , Lipossomos/química , Metotrexato/farmacocinética , Prednisolona/farmacocinética , Animais , Anti-Inflamatórios/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Quimioterapia Combinada , Humanos , Masculino , Metotrexato/administração & dosagem , Tamanho da Partícula , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Prednisolona/administração & dosagem , Ratos , Propriedades de Superfície , Distribuição Tecidual
15.
Ophthalmologica ; 242(2): 113-117, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31163427

RESUMO

PURPOSE: To evaluate the effects of repeated intra-silicone oil (SO) injections of methotrexate (MTX) on the outcomes of surgery for rhegmatogenous retinal detachment (RRD) with grade C proliferative vitreoretinopathy (PVR-C). METHODS: In this prospective pilot case series, eyes with RRD and PVR-C underwent pars plana vitrectomy and intraocular injection of SO. At the conclusion of the procedure, 250 µg of MTX was injected into the SO-filled vitreous cavity. Intra-SO injection was repeated at weeks 3 and 6; the minimum follow-up period was 6 months. The main outcome measure was retinal reattachment rate. RESULTS: Eleven eyes of 11 patients (mean age, 52.73 ± 18.01 years) were included. The mean follow-up period was 9 ± 3 months (range, 6-15 months). Total retinal detachment with anterior and/or posterior PVR-C was present in all eyes before surgery. Mean preoperative best-corrected visual acuity (BCVA) was 2.62 ± 0.04 logMAR. All operated eyes exhibited retinal reattachment posterior to the equator during the follow-up period. Mean postoperative BCVA was significantly improved to 1.02 ± 0.51 logMAR (p = 0.003). No ocular or systemic side effects were observed. CONCLUSION: Repeated intra-SO injection of MTX as an adjunctive therapy for RRD complicated by PVR showed promising results and was not associated with adverse effects. Further studies are needed to confirm its possible beneficial effects on the final anatomic and functional outcomes in these cases.


Assuntos
Metotrexato/administração & dosagem , Descolamento Retiniano/terapia , Óleos de Silicone , Acuidade Visual , Vitrectomia/métodos , Vitreorretinopatia Proliferativa/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Tamponamento Interno , Feminino , Humanos , Imunossupressores/administração & dosagem , Injeções Intraoculares , Fotocoagulação a Laser , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Retina/patologia , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Tomografia de Coerência Óptica , Resultado do Tratamento , Vitreorretinopatia Proliferativa/complicações , Vitreorretinopatia Proliferativa/diagnóstico , Adulto Jovem
16.
Medicine (Baltimore) ; 98(24): e15662, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192909

RESUMO

Primary adrenal lymphoma (PAL) is a rare entity of lymphoma with dismal prognosis using systemic chemotherapy. More clinical reports are needed to guide the treatment for PAL.We performed a retrospective analysis of 20 patients diagnosed with PAL who presented to our center between January 2005 and January 2014.Median age at presentation was 48 years (range: 27-73) with a male-to-female ratio of 7:3. Bilateral and right-sided adrenal involvement were seen in 11 of 20 and 7 of 20 patients, respectively. Adrenal insufficiency (AI) was seen in 6 of 10 evaluated patients. Diffuse large B cell lymphoma (DLBCL) was the most common immunophenotype (85.0%). Two patients died due to rapid disease progression before treatment. Two patients received autologous stem cell transplantation as consolidation therapy. All patients received prophylactic intrathecal chemotherapy. The estimated 5-year overall survival (OS) and progression-free survival (PFS) were 52.5% [95% confidence interval (95% CI: 28.2-72.0)] and 53.2% (95% CI: 29.0-72.5), respectively.These findings suggest that PAL should always be considered in differential diagnosis of adrenal mass with AI. Despite the contrasting previous reports, long-term prognosis of PAL is not necessarily inferior to that of non-Hodgkin lymphoma in general.


Assuntos
Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma Difuso de Grandes Células B/terapia , Neoplasias das Glândulas Suprarrenais/mortalidade , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/administração & dosagem , Citarabina/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Progressão da Doença , Esquema de Medicação , Tratamento Farmacológico , Feminino , Humanos , Injeções Espinhais , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento
17.
Eur J Pharm Sci ; 135: 91-102, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31078644

RESUMO

Montmorillonite Clay (MMT) is aimed to develop as an orally administrable drug delivery vehicle with enhanced efficacy. Aiming to enhance the therapeutic index of methotrexate, curcumin is concomitantly used with methotrexate in the present study. Being folate antagonist in nature, methotrexate is internalized into cells by folate receptor (FR); which is over-expressed in certain human cancer cells such as cervical carcinoma cells (HeLa). Firstly, montmorillonite Clay (MMT) is organically modified (OMMT) with cetyl trimethyl ammonium bromide (CTAB) and used to intercalate curcumin and methotrexate separately, designated as OMMT-Cur and OMMT-MTX, respectively. XRD pattern demonstrated successful intercalation of therapeutics and an increase in clay interlayer distance facilitated by CTAB. The dissolution kinetics of methotrexate follows Higuchi model for both Simulated Gastric Fluid (SGF) and Simulated Intestinal Fluid (SIF), while the release kinetics for curcumin fitted into Higuchi model for SGF and Hixson-Crowell model for SIF, respectively. OMMT-MTX are able to discriminate FR-positive HeLa cells from FR-negative breast cancer cells (MCF7); irrespective of alike cellular phenotypes. Further, the pre-treatment of HeLa cells with curcumin improves its sensitivity towards methotrexate causing a greater killing of the Hela cells. Together, the results propose the concomitant use of curcumin and methotrexate for successfully targeting highly invasive FR-positive carcinomas by means of folate receptor using MMTs.


Assuntos
Antineoplásicos/administração & dosagem , Bentonita/química , Argila/química , Curcumina/farmacologia , Portadores de Fármacos/química , Antagonistas do Ácido Fólico/administração & dosagem , Metotrexato/administração & dosagem , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Cetrimônio/química , Liberação Controlada de Fármacos , Receptor 2 de Folato/metabolismo , Antagonistas do Ácido Fólico/química , Células HeLa , Humanos , Células MCF-7 , Metotrexato/química
18.
Rinsho Shinkeigaku ; 59(6): 365-370, 2019 Jun 22.
Artigo em Japonês | MEDLINE | ID: mdl-31142712

RESUMO

A 67-year-old male was transferred to our hospital with diplopia, decreased deep tendon reflex and ataxia. He had been suspected Fisher syndrome because of previous upper respiratory tract infection. A cerebrospinal fluid examination showed marked hypoglycorrhachia, pleocytosis and elevated protein, and cytological examination suggested malignant lymphoma. Abdominal computed tomography revealed a left adrenal mass. A biopsy of the left adrenal mass revealed diffuse large B-cell lymphoma. He was treated with a combination of R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, oncovin and prednisolone) and intrathecal administration of methotrexate, cytarabine and prednisolone. Neurological symptoms were gradually improved. Malignancy should be considered in addition to bacterial, fungal or tuberculous meningitis in a case with marked hypoglycorrhachia.


Assuntos
Biomarcadores Tumorais/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/diagnóstico , Glucose/líquido cefalorraquidiano , Linfoma Difuso de Grandes Células B/líquido cefalorraquidiano , Linfoma Difuso de Grandes Células B/diagnóstico , Doenças do Nervo Oculomotor/etiologia , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/complicações , Neoplasias do Sistema Nervoso Central/patologia , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Diagnóstico por Imagem , Doxorrubicina/administração & dosagem , Humanos , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/patologia , Masculino , Metotrexato/administração & dosagem , Prednisolona/administração & dosagem , Prednisona/administração & dosagem , Resultado do Tratamento , Vincristina/administração & dosagem
19.
Immunol Med ; 42(1): 29-38, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31067155

RESUMO

The aim of this study was to assess abatacept in rheumatoid arthritis (RA) patient. Patients (20 men, 89 women, aged 61.9 ± 10.4 y) who responded inadequately to conventional synthetic disease-modifying anti-rheumatic drug were treated with abatacept for 24-months. Disease activity score in 28 joints (DAS28-CRP) was evaluated. Of 109 patients, 82 (75.2%) were on methotrexate (MTX; mean dosage 9.0 ± 2.7 mg/week); 48 (44.0%) were naive to biologics and 61 (56.0%) had failed biologics. The 1- and 2-year retention rates were 77% and 53%, respectively. At 24-months, the DAS28-CRP remission rates were 54.5% in the biologic-naïve patients, and 28.2% in the biologic-failure patients (p < .01), while the structural remission rates were 83.9% and 73.1%, respectively (p = .461). Abatacept was equally effective in RA patients who were and were not on concomitant MTX. Biologic-naïve was associated with better clinical outcome. Abatacept was effective in patients who showed decreasing anti-CCP antibody titers or serum MMP-3 levels during treatment. Infection was the most frequent adverse effect of abatacept therapy. In conclusion, abatacept is more effective in biologic-naïve than in biologic-failure RA patients with or without concomitant use of MTX. Abatacept is more effective in RA patients with than without decreasing serum MMP-3 or anti-CCP antibody titers during treatment.


Assuntos
Abatacepte/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Imunossupressores/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Anti-Proteína Citrulinada/sangue , Artrite Reumatoide/diagnóstico , Grupo com Ancestrais do Continente Asiático , Biomarcadores/sangue , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Metaloproteinase 3 da Matriz , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Indução de Remissão , Resultado do Tratamento
20.
Lancet ; 393(10188): 2303-2311, 2019 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-31130260

RESUMO

BACKGROUND: Upadacitinib, an oral Janus kinase (JAK)1-selective inhibitor, showed efficacy in combination with stable background conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in patients with rheumatoid arthritis who had an inadequate response to DMARDs. We aimed to evaluate the safety and efficacy of upadacitinib monotherapy after switching from methotrexate versus continuing methotrexate in patients with inadequate response to methotrexate. METHODS: SELECT-MONOTHERAPY was conducted at 138 sites in 24 countries. The study enrolled adults (≥18 years) who fulfilled the 2010 American College of Rheumatology (ACR)-European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis. Patients with active rheumatoid arthritis despite stable methotrexate were randomly assigned 2:2:1:1 to switch to once-daily monotherapy of of upadacitinib or to continue methotrexate at their existing dose as blinded study drug; starting from week 14, patients assigned to continue methotrexate were switched to 15 mg or 30 mg once-daily upadacitinib per prespecified random assignment at baseline. The primary endpoints in this report are proportion of patients achieving 20% improvement in the ACR criteria (ACR20) at week 14, and proportion achieving low disease activity defined as 28-joint Disease Activity Score using C-reactive protein (DAS28[CRP]) of 3·2 or lower, both with non-responder imputation at week 14. Outcomes were assessed in patients who received at least one dose of study drug. This study is active but not recruiting and is registered with ClinicalTrials.gov, number NCT02706951. FINDINGS: Patients were screened between Feb 23, 2016, and May 19, 2017 and 648 were randomly assigned to treatment. 598 (92%) completed week 14. At week 14, an ACR20 response was achieved by 89 (41%) of 216 patients (95% CI 35-48) in the continued methotrexate group, 147 (68%) of 217 patients (62-74) receiving upadacitinib 15 mg, and 153 (71%) of 215 patients (65-77) receiving upadacitinib 30 mg (p<0·0001 for both doses vs continued methotrexate). DAS28(CRP) 3·2 or lower was met by 42 (19%) of 216 (95% CI 14-25) in the continued methotrexate group, 97 (45%) of 217 (38-51) receiving upadacitinib 15 mg, and 114 (53%) of 215 (46-60) receiving upadacitinib 30 mg (p<0·0001 for both doses vs continued methotrexate). Adverse events were reported in 102 patients (47%) on continued methotrexate, 103 (47%) on upadacitinib 15 mg, and 105 (49%) on upadacitinib 30 mg. Herpes zoster was reported by one (<1%) patient on continued methotrexate, three (1%) on upadacitinib 15 mg, and six (3%) on upadacitinib 30 mg. Three malignancies (one [<1%] on continued methotrexate, two [1%] on upadacitinib 15 mg), three adjudicated major adverse cardiovascular events (one [<1%] on upadacitinib 15 mg, two [<1%] on upadacitinib 30 mg), one adjudicated pulmonary embolism (<1%; upadacitinib 15 mg), and one death (<1%; upadacitinib 15 mg, haemorrhagic stroke [ruptured aneurysm]) were reported in the study. INTERPRETATION: Upadacitinib monotherapy showed statistically significant improvements in clinical and functional outcomes versus continuing methotrexate in this methotrexate inadequate-responder population. Safety observations were similar to those in previous upadacitinib rheumatoid arthritis studies. FUNDING: AbbVie Inc, USA.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Inibidores de Janus Quinases/administração & dosagem , Adulto , Idoso , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Proteína C-Reativa/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Inibidores de Janus Quinases/efeitos adversos , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Indução de Remissão , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA