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1.
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
2.
Am J Vet Res ; 80(8): 743-755, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31339769

RESUMO

OBJECTIVE: To evaluate the clinicopathologic, hemodynamic, and echocardiographic effects of short-term administration of anti-inflammatory dosages of prednisolone to systemically normal cats. ANIMALS: 10 cats with allergic dermatitis and 10 healthy control cats. PROCEDURES: Cats with allergic dermatitis were randomly allocated to 2 groups and received 2 dosages of prednisolone (1 and 2 mg/kg/d, PO, for 7 days) in a crossover design followed by 9-day tapering and 14-day washout periods. Each prednisolone-treated cat was matched to a healthy control cat on the basis of sex, neuter status, age (± 1 year), and body weight (± 10%). Control cats received no treatment during the 35-day observation period. Clinicopathologic, echocardiographic, and hemodynamic variables were measured at baseline (day 0) and predetermined times during and after prednisolone administration and compared within and between the 2 treatment groups. RESULTS: Prednisolone-treated cats had expected clinicopathologic alterations (mild increases in neutrophil and monocyte counts and serum concentrations of albumin, cholesterol, and triglycerides) but systolic arterial blood pressure; blood glucose, serum potassium, and cardiac biomarker concentrations; urinary sodium excretion; and echocardiographic variables did not differ significantly from baseline at any time. Statistically significant, albeit clinically irrelevant, increases in blood glucose and N-terminal pro-B-type natriuretic peptide concentrations were observed between baseline and the prednisolone pharmacokinetic steady state (7 days after initiation) only when the 2-mg/kg dosage was administered. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated short-term oral administration of anti-inflammatory dosages of prednisolone did not cause relevant hemodynamic, echocardiographic, or diabetogenic effects in systemically normal cats with allergic dermatitis.


Assuntos
Anti-Inflamatórios/farmacologia , Gatos , Glucocorticoides/farmacologia , Prednisolona/farmacologia , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Doenças do Gato/tratamento farmacológico , Dermatite/tratamento farmacológico , Dermatite/veterinária , Ecocardiografia/efeitos dos fármacos , Ecocardiografia/veterinária , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Hemodinâmica/efeitos dos fármacos , Masculino , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Estudos Prospectivos , Distribuição Aleatória
3.
BMJ ; 365: l1800, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31335316

RESUMO

OBJECTIVE: To determine whether extending initial prednisolone treatment from eight to 16 weeks in children with idiopathic steroid sensitive nephrotic syndrome improves the pattern of disease relapse. DESIGN: Double blind, parallel group, phase III randomised placebo controlled trial, including a cost effectiveness analysis. SETTING: 125 UK National Health Service district general hospitals and tertiary paediatric nephrology centres. PARTICIPANTS: 237 children aged 1-14 years with a first episode of steroid sensitive nephrotic syndrome. INTERVENTIONS: Children were randomised to receive an extended 16 week course of prednisolone (total dose 3150 mg/m2) or a standard eight week course of prednisolone (total dose 2240 mg/m2). The drug was supplied as 5 mg tablets alongside matching placebo so that participants in both groups received the same number of tablets at any time point in the study. A minimisation algorithm ensured balanced treatment allocation by ethnicity (South Asian, white, or other) and age (5 years or less, 6 years or more). MAIN OUTCOME MEASURES: The primary outcome measure was time to first relapse over a minimum follow-up of 24 months. Secondary outcome measures were relapse rate, incidence of frequently relapsing nephrotic syndrome and steroid dependent nephrotic syndrome, use of alternative immunosuppressive treatment, rates of adverse events, behavioural change using the Achenbach child behaviour checklist, quality adjusted life years, and cost effectiveness from a healthcare perspective. Analysis was by intention to treat. RESULTS: No significant difference was found in time to first relapse (hazard ratio 0.87, 95% confidence interval 0.65 to 1.17, log rank P=0.28) or in the incidence of frequently relapsing nephrotic syndrome (extended course 60/114 (53%) v standard course 55/109 (50%), P=0.75), steroid dependent nephrotic syndrome (48/114 (42%) v 48/109 (44%), P=0.77), or requirement for alternative immunosuppressive treatment (62/114 (54%) v 61/109 (56%), P=0.81). Total prednisolone dose after completion of the trial drug was 6674 mg for the extended course versus 5475 mg for the standard course (P=0.07). There were no statistically significant differences in serious adverse event rates (extended course 19/114 (17%) v standard course 27/109 (25%), P=0.13) or adverse event rates, with the exception of behaviour, which was poorer in the standard course group. Scores on the Achenbach child behaviour checklist did not, however, differ. Extended course treatment was associated with a mean increase in generic quality of life (0.0162 additional quality adjusted life years, 95% confidence interval -0.005 to 0.037) and cost savings (difference -£1673 ($2160; €1930), 95% confidence interval -£3455 to £109). CONCLUSIONS: Clinical outcomes did not improve when the initial course of prednisolone treatment was extended from eight to 16 weeks in UK children with steroid sensitive nephrotic syndrome. However, evidence was found of a short term health economic benefit through reduced resource use and increased quality of life. TRIAL REGISTRATION: ISRCTN16645249; EudraCT 2010-022489-29.


Assuntos
Assistência de Longa Duração , Síndrome Nefrótica , Prednisolona , Qualidade de Vida , Prevenção Secundária , Adolescente , Criança , Pré-Escolar , Análise Custo-Benefício , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Monitoramento de Medicamentos/métodos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Glucocorticoides/economia , Humanos , Imunossupressores/uso terapêutico , Lactente , Análise de Intenção de Tratamento , Assistência de Longa Duração/economia , Assistência de Longa Duração/métodos , Masculino , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/economia , Síndrome Nefrótica/psicologia , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Prednisolona/economia , Prevenção Secundária/economia , Prevenção Secundária/métodos , Resultado do Tratamento
4.
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
5.
J Dermatol ; 46(7): 626-630, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31149739

RESUMO

Morphea profunda is a rare subtype of localized scleroderma and it is difficult to evaluate the conditions of sclerotic changes at an early stage. Studies using ultrasonography to evaluate localized scleroderma are limited and, to date, the characteristic findings of morphea profunda assessed by ultrasonography have never been reported. Here, we present a case of morphea profunda diagnosed with the assistance of ultrasonography. A 69-year-old Japanese woman with a past history of morphea en plaque on her lower abdomen presented with skin indurations of her bilateral lower back and thighs. To evaluate the stiffness of the subcutis, fascia and muscle, we utilized ultrasonography and found an unexpected hyperechogenicity not only of the dermis but also in the deeper tissue. The diagnosis was revised to morphea profunda after we performed a deep skin biopsy, including the muscle tissue. From this case, we assert that ultrasonography is a useful alternative tool to assist in the differential diagnosis of morphea profunda.


Assuntos
Músculo Esquelético/patologia , Esclerodermia Localizada/diagnóstico por imagem , Pele/patologia , Tela Subcutânea/patologia , Administração Oral , Idoso , Biópsia/métodos , Diagnóstico Diferencial , Feminino , Fibrose , Humanos , Músculo Esquelético/diagnóstico por imagem , Prednisolona/administração & dosagem , Esclerodermia Localizada/patologia , Pele/diagnóstico por imagem , Tela Subcutânea/diagnóstico por imagem , Resultado do Tratamento , Ultrassonografia/instrumentação , Ultrassonografia/métodos
6.
J Dermatol ; 46(8): 716-719, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31180164

RESUMO

Pyrexia is the most common adverse event in patients with melanoma or other solid organ malignancies that are treated with the combination of dabrafenib and trametinib (combi-DT). Given the expanded indication for combi-DT, management of pyrexia is a high priority. No previous case series has revealed which blood markers reflect the course of pyrexia and there is no consensus on the management strategy for pyrexia. The current case series study describes the utility of neutrophil count (NC), neutrophil ratio (NR) and C-reactive protein (CRP) in 11 patients with metastatic melanoma and BRAF V600 mutations who experienced pyrexia during combi-DT in our department. We also described the clinical course of pyrexia episodes that were managed with the concomitant use of oral prednisolone and immediate withdrawal of combi-DT. Consequently, the analysis of 37 pyrexia episodes in 11 patients showed that the differences in NC, NR and CRP at the onset of pyrexia were significantly different from those at pyretolysis (P = 0.01, 0.006 and 0.03, respectively). Additionally, in the 24 pyrexia episodes treated with the concomitant use of oral prednisolone and the immediate withdrawal of combi-DT, the mean duration of pyrexia and the mean time to restart combi-DT were 3 and 6 days, respectively. Therefore, the blood markers that reflect the course of pyrexia during combi-DT may be helpful for the appropriate management of pyrexia; also, our management strategy for pyrexia successfully reduced the duration of pyrexia and did not require a long-term drug holiday. Further large-scale studies are required to verify our results.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Proteína C-Reativa/análise , Febre/diagnóstico , Imidazóis/efeitos adversos , Neutrófilos , Oximas/efeitos adversos , Piridonas/efeitos adversos , Pirimidinonas/efeitos adversos , Administração Oral , Adulto , Idoso , Biomarcadores/sangue , Estudos de Viabilidade , Feminino , Febre/sangue , Febre/induzido quimicamente , Febre/tratamento farmacológico , Humanos , Contagem de Leucócitos , Masculino , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
7.
Rinsho Shinkeigaku ; 59(7): 431-435, 2019 Jul 31.
Artigo em Japonês | MEDLINE | ID: mdl-31243249

RESUMO

A 53-year-old man suffering from squamous cell lung cancer presented with bilateral ptosis and bulbar palsy a month after initial treatment with the immune checkpoint inhibitor nivolumab. The symptoms showed worsening from midday, suggesting myasthenia gravis (MG), although anti-AChR antibody was negative. Although no muscle weakness was detected, the CK level was elevated to 5,255 IU/l, and MRI of the thigh revealed inflammation of the bilateral rectus femoris muscle. A muscle biopsy showed signs of necrotizing myopathy with expression of sarcolemmal HLA class I and accumulation of macrophages, CD4, CD8, and CD20-positive lymphocytes. Positivity for anti-titin antibody, one of the anti-striated muscle antibodies, was evident. The patient was diagnosed as having nivolumab-related necrotizing myopathy with myasthenia gravis, an immune-related adverse event (irAE). Treatment with prednisolone rapidly ameliorated the symptoms, and the serum CK level normalized. There have been several reports of nivolumab-related myositis with MG. On the basis of the muscle pathology and antibody data, we were able to clarify that necrotizing myopathy was related to the pathogenesis of this case.


Assuntos
Conectina/imunologia , Doenças Musculares/induzido quimicamente , Miastenia Gravis/induzido quimicamente , Nivolumabe/efeitos adversos , Autoanticorpos/sangue , Biomarcadores/sangue , Carcinoma de Células Escamosas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Doenças Musculares/diagnóstico , Doenças Musculares/tratamento farmacológico , Doenças Musculares/patologia , Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamento farmacológico , Necrose , Nivolumabe/uso terapêutico , Prednisolona/administração & dosagem , Músculo Quadríceps/patologia , Resultado do Tratamento
8.
Immunol Med ; 42(1): 45-49, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31204589

RESUMO

A healthy 32-year-old man had a fever and elevated levels of white blood cells (WBC) and C-reactive protein (CRP). In addition, he presented with a skin rash on his forehead, around the neck, and from the anterior chest to the abdomen. His laboratory findings showed elevated levels of hepatic enzyme, CRP, and ferritin; therefore, he was suspected to have adult-onset Still's disease (AOSD) and referred to our department. We ruled out hematological malignancy and established diagnosis of AOSD according to Yamaguchi's criteria and treated with 20 mg/day prednisolone. His clinical condition did not improve, therefore, we increased the dosage of prednisolone to 40 mg/day; however, his rash gradually expanded with papules and plaques. A cervical skin biopsy revealed neutrophil dermatosis and analysis of the MEFV gene revealed a heterozygous variant in exon 2 (E148Q). We found an elevated percentage of CD86+CD14+CD16- classical monocytes in the peripheral blood using flow cytometry. We added oral potassium iodide as a treatment for neutrophil dermatosis. Despite this treatment, his eruption and fever did not subside, therefore, we changed potassium iodide to colchicine, this improved his clinical condition. This case suggests the importance of autoinflammation-related gene abnormalities and macrophage activation in the pathogenesis of neutrophil dermatosis.


Assuntos
Variação Genética , Ativação de Macrófagos , Monócitos/imunologia , Pirina/genética , Síndrome de Sweet/genética , Síndrome de Sweet/imunologia , Administração Oral , Adulto , Colchicina/administração & dosagem , Quimioterapia Combinada , Humanos , Masculino , Iodeto de Potássio/administração & dosagem , Prednisolona/administração & dosagem , Doença de Still de Início Tardio , Síndrome de Sweet/sangue , Síndrome de Sweet/tratamento farmacológico , Resultado do Tratamento
9.
J Laryngol Otol ; 133(7): 566-570, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31182177

RESUMO

BACKGROUND: There are no definite guidelines regarding the most adequate steroid regimens for acute acoustic trauma. OBJECTIVE: To elucidate the dose-dependent differing benefits of oral steroids on hearing improvement following acute acoustic trauma. METHODS: Twenty-nine patients treated with oral steroids following a diagnosis of unilateral acute acoustic trauma were retrospectively reviewed. Patients were sorted into two groups with an oral steroid regimen. Group 1 received a 14-day course of treatment: 60 mg prednisolone daily for 10 days, tapering off over days 11-14. Group 2 received prednisolone for a total of 10 days: 60 mg for 5 days, tapering down each day for the remainder. Multivariable linear regression analysis was performed to evaluate the factors associated with the hearing gain. RESULTS: In the multivariable regression (R2 = 0.51, p < 0.001), patients in group 1 showed more significant improvement in the degree of hearing gain compared to group 2 (p = 0.03). CONCLUSION: After comparing the differing benefits of oral steroids on hearing improvement by dosage, we recommend a high dose of prednisolone (60 mg per day) for 10 days, tapering over the remaining 4 days, for better hearing recovery following acute acoustic trauma.


Assuntos
Perda Auditiva Provocada por Ruído/tratamento farmacológico , Prednisolona/administração & dosagem , Esteroides/administração & dosagem , Administração Oral , Esquema de Medicação , Feminino , Violência com Arma de Fogo , Testes Auditivos , Humanos , Masculino , Prednisolona/uso terapêutico , Estudos Retrospectivos , Esteroides/uso terapêutico , Resultado do Tratamento
10.
Clin Biochem ; 69: 8-14, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31077643

RESUMO

BACKGROUND: This study aimed to evaluate the relationships between concomitant biologic disease-modifying anti-rheumatic drugs (DMARDs) and prednisolone administration and blood tacrolimus exposure or serum CYP3A4/5-related markers in rheumatoid arthritis (RA) patients without severe disease activity. METHODS: Forty-six RA patients treated with oral tacrolimus once daily for maintenance of clinical remission to moderate disease activity were enrolled. The blood concentrations of tacrolimus and its major metabolite were determined at 12 h after the evening dosing. Blood samples for determination of serum markers including 4ß-hydroxycholesterol (4ß-OHC), 25-hydroxyvitamin D (25-OHD) and interleukin-6 (IL-6), and CYP3A5 genotype were collected. RESULTS: Most enrolled patients had RA with clinical remission to mild disease activity. Concomitant tocilizumab or low-dose prednisolone administration did not alter the blood tacrolimus exposure. Serum 4ß-OHC level was lower in tocilizumab co-treated patients than in the biologic DMARD non-treated patients. The blood tacrolimus concentration was inversely correlated with the serum level of 25-OHD, but not 4ß-OHC and IL-6. The serum level of 4ß-OHC was positively associated with that of 25-OHD. No correlations were observed between the serum levels of CYP3A4/5 activity markers and IL-6. The patients with the homozygous CYP3A5*3 had the higher blood tacrolimus concentration, while CYP3A5*3 allele was not associated with the serum levels of 4ß-OHC and 25-OHD. CONCLUSIONS: Concomitant use of tocilizumab or low-dose prednisolone had no effect on the pharmacokinetics of tacrolimus, while tocilizumab lowered serum 4ß-OHC. Blood tacrolimus exposure was negatively associated with serum 25-OHD in RA patients with clinical remission to moderate disease activity.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Citocromo P-450 CYP3A/sangue , Imunossupressores/uso terapêutico , Prednisolona/uso terapêutico , Tacrolimo/uso terapêutico , Idoso , Antirreumáticos/administração & dosagem , Artrite Reumatoide/enzimologia , Biomarcadores/sangue , Feminino , Humanos , Hidroxicolesteróis/sangue , Imunossupressores/sangue , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Tacrolimo/administração & dosagem , Vitamina D/análogos & derivados , Vitamina D/sangue
11.
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
12.
Ann Otol Rhinol Laryngol ; 128(6_suppl): 134S-138S, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31092042

RESUMO

OBJECTIVES: Glucocorticoids are given for sensorineural hearing loss, but little is known of their molecular impact on the inner ear. Furthermore, in spite of claims of improved hearing recovery with intratympanic delivery of steroids, no studies have actually documented the inner ear molecular functions that are enhanced with this delivery method. METHODS: To assess steroid-driven processes in the inner ear, gene chip analyses were conducted on mice treated systemically with the glucocorticoids prednisolone or dexamethasone or the mineralocorticoid aldosterone. Other mice were given the same steroids intratympanically. Inner ears were harvested at 6 hours and processed on the Affymetrix 430 2.0 Gene Chip for expression of its 34 000 genes. Results were statistically analyzed for up or down expression of each gene against control (untreated) mice. RESULTS: Analyses showed approximately 17 500 genes are normally expressed in the inner ear and steroids alter expression of 55% to 82% of these. Dexamethasone changed expression of 9424 (53.9%) inner ear genes following systemic injection but 14 899 ear genes (85%) if given intratympanically. A similar pattern was seen with prednisolone, as 7560 genes were impacted by oral delivery and 11 164 genes (63.8%) when given intratympanically. The mineralocorticoid aldosterone changed expression of only 268 inner ear genes if given orally, but this increased to 10 124 genes (57.9%) if injected intratympanically. Furthermore, the glucocorticoids given actually impacted more inner ear genes via the mineralocorticoid receptor than the glucocorticoid receptor. CONCLUSIONS: Thousands of inner ear genes were affected by steroids, and this number increased significantly if steroids were delivered intratympanically. Also, the impact of glucocorticoids on inner ear mineralocorticoid functions is more substantial than previously known. Thus, the application of therapeutic steroids for hearing loss needs to be reassessed in light of their more comprehensive impact on inner ear genes. Furthermore, simply ascribing the efficacy of steroids to immunosuppression no longer appears to be warranted.


Assuntos
Dexametasona/administração & dosagem , Orelha Interna/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/administração & dosagem , Prednisolona/administração & dosagem , Animais , Injeção Intratimpânica , Camundongos , Camundongos Endogâmicos BALB C , Análise de Sequência com Séries de Oligonucleotídeos
13.
Medicine (Baltimore) ; 98(18): e15237, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045763

RESUMO

RATIONALE: Idiopathic multicentric Castleman disease (iMCD) is a systemic disease with multiple regions of lymphadenopathy and systemic symptoms and associated with rheumatoid arthritis (RA) and collagen diseases. However, few reported have described the coexistence of iMCD and RA and the mechanisms by which iMCD induces arthritis remain elusive. We experienced a rare case of iMCD, wherein the patient exhibited symptoms of polyarthritis with high-grade fever. PATIENT CONCERNS: A 34-year-old woman was admitted to our hospital for further evaluation of a high fever with polyarthritis. The levels of both rheumatoid factor and anticitrullinated protein antibody were negative. F-fluorodeoxyglucose/positron emission tomography-computed tomography showed lymphadenopathy with increased fluoro-2-deoxy-D-glucose uptake. Magnetic resonance imaging and musculoskeletal ultrasonography revealed active synovitis in the hands which was consistent with RA. DIAGNOSES: We diagnosed iMCD based on human herpesvirus 8 negativity, HIV negativity, systemic lymphadenopathy, and pathologic findings of the lymph nodes. The patient did not satisfy the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for RA. Cytokine assay showed elevated serum levels of interleukin-17 and CXCL10, comparable to those in patients with RA. INTERVENTIONS: We administered 15 mg/d of predonisolone. OUTCOMES: After this treatment, the patient's symptoms showed improvement. As of this writing, we tapered the prednisolone to 7.5 mg/d, and the patient's remission has been maintained for >4 months. LESSONS: The present case suggests that RA-like active synovitis may coexist in iMCD, resulting from aberrant T-cell activation and histologic examination using lymph node biopsy may help enable early diagnosis of iMCD.


Assuntos
Artrite Reumatoide/complicações , Hiperplasia do Linfonodo Gigante/complicações , Linfadenopatia/diagnóstico por imagem , Sinovite/diagnóstico por imagem , Adulto , Artrite/diagnóstico , Artrite/etiologia , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/patologia , Hiperplasia do Linfonodo Gigante/sangue , Hiperplasia do Linfonodo Gigante/tratamento farmacológico , Hiperplasia do Linfonodo Gigante/patologia , Quimiocina CXCL10/sangue , Diagnóstico Diferencial , Feminino , Febre/diagnóstico , Febre/etiologia , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Herpesvirus Humano 8 , Humanos , Interleucina-17/sangue , Linfadenopatia/patologia , Imagem por Ressonância Magnética/métodos , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Sinovite/patologia , Linfócitos T/patologia , Resultado do Tratamento
14.
Medicine (Baltimore) ; 98(18): e15329, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045771

RESUMO

RATIONALE: Gain of function (GOF) mutations in PIK3CD gene encoding PI3K p110δ were recently associated with a novel combined immune deficiency characterized by recurrent sinopulmonary infections, CD4 lymphopenia, reduced class-switched memory B cells, lymphadenopathy, cytomegalovirus and/or epstein-Barr virus (EBV) viremia, and EBV-related lymphoma. A subset of affected patients also had elevated serum IgM. PATIENT CONCERNS: We report a patient who was diagnosed with systemic lupus erythematosus (SLE) at a young age and was recently found to carry heterozygous mutations in PIK3CD. The patient not only presented with recurrent sinopulmonary infections, CD4 lymphopenia, lymphadenopathy, EBV viremia, and elevated serum IgM, but also met classification criteria of SLE based on persistent proteinuria and hematuria, leukopenia and anemia, low level of serum complement, and positive autoantibody for antinuclear antibodies. DIAGNOSES: Activated PI3Kδ syndrome. INTERVENTIONS: Oral prednisolone and hydroxychloroquine combined with mycophenolate mofetil was given to the patient. He was currently receiving intravenous immunoglobulin per month in association with hydroxychloroquine, low-dose prednisolone, and mycophenolate mofetil. OUTCOMES: At present, the level of complement restored to normal, hematuria and proteinuria disappeared, and liver function returned to normal. LESSONS: SLE may be a novel phenotype of GOF mutation in PI3CKD gene (GOF PIK3CD).


Assuntos
Classe I de Fosfatidilinositol 3-Quinases/genética , Mutação com Ganho de Função/genética , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/genética , Lúpus Eritematoso Sistêmico/genética , Adolescente , Anticorpos Antinucleares/sangue , Grupo com Ancestrais do Continente Asiático/genética , Classe I de Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Proteínas do Sistema Complemento/análise , Proteínas do Sistema Complemento/efeitos dos fármacos , Inibidores Enzimáticos/uso terapêutico , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/etiologia , Infecções por Vírus Epstein-Barr/imunologia , Glucocorticoides/uso terapêutico , Herpesvirus Humano 4/imunologia , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/etiologia , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/uso terapêutico , Fenótipo , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico
15.
Rinsho Shinkeigaku ; 59(5): 268-273, 2019 May 28.
Artigo em Japonês | MEDLINE | ID: mdl-31061305

RESUMO

A 61-year-old woman presented with acute intense lower back pain and weakness in her left leg. She also presented with throbbing headache on the same day. On admission, muscle weakness in her left leg, lower left quadrantanopia and left lower extremity deep sensory disturbance were observed. Laboratory data showed no coagulopathy and autoimmune antibody was negative. Cerebrospinal fluid examination showed bloody and inflammatory findings. Brain MRI revealed cerebral infarction with multiple intracranial arterial stenosis and convexal subarachnoid hemorrhage. Spinal MRI revealed spinal hemorrhage in the cervical, thoracic, and part of the lumbar spine. Because these lesions occurred simultaneously, we made a diagnosis of vasculitis. After high dose corticosteroids therapy was undertaken, the multiple arterial stenosis improved. Primary angiitis of the central nervous system is sometimes difficult to distinguish from reversible cerebral vasoconstriction syndrome in its initial stage; although symptoms, examination findings and treatment differ in both.


Assuntos
Infarto Cerebral/etiologia , Hemorragia/etiologia , Doenças da Medula Espinal/etiologia , Vasculite do Sistema Nervoso Central/complicações , Vasculite do Sistema Nervoso Central/tratamento farmacológico , Dor nas Costas/etiologia , Infarto Cerebral/diagnóstico por imagem , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética , Feminino , Cefaleia/etiologia , Hemorragia/diagnóstico por imagem , Humanos , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Pulsoterapia , Índice de Gravidade de Doença , Doenças da Medula Espinal/diagnóstico por imagem , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/etiologia , Resultado do Tratamento , Vasculite do Sistema Nervoso Central/diagnóstico
16.
Rinsho Shinkeigaku ; 59(5): 274-278, 2019 May 28.
Artigo em Japonês | MEDLINE | ID: mdl-31061306

RESUMO

Hemolytic uremic syndrome (HUS) and acute encephalopathy caused by enterohemorrhagic Escherichia coli infection occur commonly in children, whereas adult-onset disease is rare. Here we report the case of a 24-year-old woman who developed acute encephalopathy and recovered without sequelae. She initially developed abdominal pain and diarrhea. On day 6, O-157 Shiga toxin was detected in her stool and she developed HUS. On day 11, acute encephalopathy developed and she required artificial ventilation. She was treated with steroid pulse therapy and plasma exchange (PE) and then discharged on day 53 without any sequelae. Globotriaosylceramide, a Shiga toxin receptor, is more frequently present on the cellular membranes of women than on those of men. Therefore, it is conceivable that adult women are at a higher risk of developing acute encephalopathy than men. Steroid pulse therapy and PE may effectively treat acute encephalopathy by reducing inflammatory cytokine levels in the blood; therefore, these treatments should be proactively considered.


Assuntos
Encefalopatias/etiologia , Encefalopatias/terapia , Escherichia coli Êntero-Hemorrágica , Infecções por Escherichia coli/complicações , Síndrome Hemolítico-Urêmica/etiologia , Síndrome Hemolítico-Urêmica/terapia , Doença Aguda , Antígenos Glicosídicos Associados a Tumores , Escherichia coli Êntero-Hemorrágica/isolamento & purificação , Feminino , Humanos , Metilprednisolona/administração & dosagem , Troca Plasmática , Prednisolona/administração & dosagem , Pulsoterapia , Risco , Toxina Shiga/isolamento & purificação , Resultado do Tratamento , Triexosilceramidas , Adulto Jovem
17.
Tidsskr Nor Laegeforen ; 139(7)2019 Apr 09.
Artigo em Norueguês, Inglês | MEDLINE | ID: mdl-30969044

RESUMO

BACKGROUND: Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, has a predilection for the upper airways, lungs and kidneys. However, any other organ can be affected. Although cutaneous lesions are common, they have only rarely been reported as a primary manifestation of the disease. CASE PRESENTATION: We present a case of a teenage boy with pyoderma gangrenosum-like ulcerations of the neck and face. Anti-neutrophil cytoplasmic antibody with antigen specificity for proteinase 3 (PR3-ANCA) was detected. In the absence of other symptoms and organ manifestations, the ulcerations were still considered to be pyoderma gangrenosum. The ulcers started to heal during treatment with corticosteroids and infliximab. One month later the patient developed sinusitis, and eventually lost vision in his left eye. The diagnosis was changed to GPA and he started treatment with methylprednisolone, rituximab and cyclophosphamide with good response on vision, sinusitis and ulcerations. INTERPRETATION: Recognition of this rare skin presentation of GPA is essential, to prevent delays in diagnosis and treatment that can lead to organ damage.


Assuntos
Face/patologia , Granulomatose com Poliangiite , Pescoço/patologia , Úlcera Cutânea/etiologia , Adolescente , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/uso terapêutico , Diagnóstico Diferencial , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/patologia , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/uso terapêutico , Infliximab/administração & dosagem , Infliximab/uso terapêutico , Masculino , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Pioderma Gangrenoso/diagnóstico , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/patologia
18.
J Dermatol ; 46(6): 535-539, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31021010

RESUMO

Pegylated liposomal doxorubicin (PLD) is an anthracycline anticancer agent used in ovarian cancer and a form of doxorubicin enclosed in pegylated liposomes. There are only a few reports on intertrigo-like eruptions caused by PLD. We describe the first case of severe bullous erythema, including intertrigo-like eruptions with angioedema, induced by PLD in Japan. We present the case of a 53-year-old woman who was diagnosed with stage IIIC ovarian cancer. After receiving three cycles of PLD, the patient developed swelling of the upper lip and painful erythema with blisters and erosions on the axilla, upper back, flank and wrists. The patient was diagnosed with angioedema and severe skin lesions, including intertrigo-like eruptions induced by PLD. Although treatment with oral prednisolone and topical steroids was effective against these eruptions, the administration of PLD was discontinued because of its ineffectiveness against the primary disease. Several risk factors, such as obesity, perspiration and racial differences, may contribute toward a severe manifestation such as that seen in our patient. Moreover, our case was the first accompanied by angioedema. The mechanism of coexistence of intertrigo-like eruptions and angioedema is not clear; further studies are required to clarify the pathological mechanism of intertrigo-like eruptions.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Doxorrubicina/análogos & derivados , Erupção por Droga/etiologia , Prednisolona/administração & dosagem , Administração Oral , Angioedema/induzido quimicamente , Angioedema/diagnóstico , Angioedema/tratamento farmacológico , Angioedema/patologia , Vesícula/induzido quimicamente , Vesícula/diagnóstico , Vesícula/tratamento farmacológico , Vesícula/patologia , Doxorrubicina/efeitos adversos , Erupção por Droga/diagnóstico , Erupção por Droga/tratamento farmacológico , Erupção por Droga/patologia , Eritema/induzido quimicamente , Eritema/diagnóstico , Eritema/tratamento farmacológico , Eritema/patologia , Feminino , Humanos , Intertrigo/induzido quimicamente , Intertrigo/diagnóstico , Intertrigo/tratamento farmacológico , Intertrigo/patologia , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Polietilenoglicóis/efeitos adversos , Pele/efeitos dos fármacos , Pele/patologia , Resultado do Tratamento
19.
BMJ Case Rep ; 12(4)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31023740

RESUMO

Gingival pathology is a daily presentation, however a small number of systemic conditions can manifest similar to a common gingival condition and have fatal results. Dentist referred 56-year-old woman to Oral and Maxillofacial Surgery department with a 2-week medical history of gingival bleeding not responding to local measures. Biopsy showed eosinophilic infiltrate and vasculitis, and blood tests showed positive markers including cytoplasmic antineutrophil cytoplasmatic antibodies. Granulomatosis with polyangiitis is a rare disease affecting the respiratory tract, blood vessels and kidneys. Oral lesions are rarely the primary presenting feature. When left untreated, most cases are fatal within a year of diagnosis. The diagnosis can only be made when certain criteria are found, including granular oral lesions exhibiting an eosinophilic inflammatory infiltrate on biopsy. With 5% of cases showing intraoral lesions as the primary feature, it is essential that dentists have the knowledge of this rare disease to refer and not to treat as a common gingival condition.


Assuntos
Odontólogos/educação , Doenças da Gengiva/diagnóstico , Granulomatose com Poliangiite/patologia , Úlceras Orais/etiologia , Assistência ao Convalescente , Antibacterianos/uso terapêutico , Anticorpos Anticitoplasma de Neutrófilos/metabolismo , Biópsia , Diagnóstico Diferencial , Eosinófilos/patologia , Feminino , Células Gigantes de Corpo Estranho/patologia , Doenças da Gengiva/patologia , Glucocorticoides/uso terapêutico , Granulomatose com Poliangiite/sangue , Granulomatose com Poliangiite/tratamento farmacológico , Hemorragia/diagnóstico , Hemorragia/etiologia , Humanos , Pessoa de Meia-Idade , Úlceras Orais/diagnóstico , Úlceras Orais/tratamento farmacológico , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Doenças Raras , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
20.
Asian Pac J Cancer Prev ; 20(4): 1171-1176, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31030491

RESUMO

Objective: Chemotherapy is the most widely recognized technique to regard leukemia and also different sorts of human tumors. In any case, tranquilize protection has stayed as the primary test against the adequacy of medications. Besides, having different unfriendly impacts, chemotherapy drugs are getting to be traded by characteristic modalities for growth treatment. In such manner, natural segments, for example, resveratrol and prednisolone have been recognized to sharpen the leukemic cells to modified cell demise through an arrangement of complex procedures. In this investigation, we have analyzed effect of 15, 50 and 100µM of resveratrol and 700µM of prednisolone on the human multidrug protection quality 1 (MDR1) as a notable marker for cell sedate protection. We assessed the impact of resveratrol and prednisolone on MDR1 protein expression in the CCRF-CEM cell line as an agent for intense lymphoblastic leukemia. The investigation was planned to clear up whether. Materials and methods: CCRF-CEM cells linage get under drug treatment with use of resveratrol and prednisolone. Western blot use at 24 and 48 hours with different doses of resveratrol and prednisolone to analysis of MDR1 expression changes. Results: Effect of 15, 50, and 100 micro molar of resveratrol and 700 micro molars of prednisolone on CCRF-CEM cells led to the MDR1 decrease. Western blot use for evaluation of MDR1 protein expression changes. Conclusion: In the present study, we observed that resveratrol and prednisolone, with a dose-dependent effect, can reduce the expression of the MDR1 protein. This reduction of expression demonstrates that resveratrol and prednisolone can overcome to drug resistance created by MDR1.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Apoptose , Proliferação de Células , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Prednisolona/administração & dosagem , Resveratrol/administração & dosagem , Células Tumorais Cultivadas
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