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1.
Proc Natl Acad Sci U S A ; 115(1): 204-209, 2018 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-29203662

RESUMO

Strongyloides stercoralis hyperinfection causes high mortality rates in humans, and, while hyperinfection can be induced by immunosuppressive glucocorticoids, the pathogenesis remains unknown. Since immunocompetent mice are resistant to infection with S. stercoralis, we hypothesized that NSG mice, which have a reduced innate immune response and lack adaptive immunity, would be susceptible to the infection and develop hyperinfection. Interestingly, despite the presence of large numbers of adult and first-stage larvae in S. stercoralis-infected NSG mice, no hyperinfection was observed even when the mice were treated with a monoclonal antibody to eliminate residual granulocyte activity. NSG mice were then infected with third-stage larvae and treated for 6 wk with methylprednisolone acetate (MPA), a synthetic glucocorticoid. MPA treatment of infected mice resulted in 50% mortality and caused a significant >10-fold increase in the number of parasitic female worms compared with infected untreated mice. In addition, autoinfective third-stage larvae, which initiate hyperinfection, were found in high numbers in MPA-treated, but not untreated, mice. Remarkably, treatment with Δ7-dafachronic acid, an agonist of the parasite nuclear receptor Ss-DAF-12, significantly reduced the worm burden in MPA-treated mice undergoing hyperinfection with S. stercoralis Overall, this study provides a useful mouse model for S. stercoralis autoinfection and suggests a therapeutic strategy for treating lethal hyperinfection.


Assuntos
Colestenos/farmacologia , Metilprednisolona/análogos & derivados , Strongyloides stercoralis/imunologia , Estrongiloidíase/tratamento farmacológico , Estrongiloidíase/imunologia , Animais , Colestenos/efeitos adversos , Feminino , Metilprednisolona/efeitos adversos , Metilprednisolona/farmacologia , Acetato de Metilprednisolona , Camundongos , Estrongiloidíase/patologia
2.
Australas J Dermatol ; 62(1): e95-e97, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32935855

RESUMO

Bullous pemphigoid is rarely seen in adolescence, and its presentation, clinical course, and treatment can differ to that found in other age groups. We present a case of bullous pemphigoid in a 16-year-old with features of koebnerisation and oral mucosal involvement and provide a brief review of paediatric bullous pemphigoid.


Assuntos
Penfigoide Bolhoso/patologia , Adolescente , Anti-Inflamatórios/uso terapêutico , Antibióticos Antituberculose/uso terapêutico , Betametasona/análogos & derivados , Betametasona/uso terapêutico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Metilprednisolona/análogos & derivados , Metilprednisolona/uso terapêutico , Ácido Micofenólico/uso terapêutico , Penfigoide Bolhoso/tratamento farmacológico , Prednisona/uso terapêutico
3.
Biotechnol Bioeng ; 117(4): 901-911, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31814109

RESUMO

Synthetic glucocorticoids such as methylprednisolone are compounds of fundamental interest to the pharmaceutical industry as their modifications within the sterane scaffold lead to higher inflammatory potency and reduced side effects compared with their parent compound cortisol. In methylprednisolone production, the complex chemical hydroxylation of its precursor medrane in position C21 exhibits poor stereo- and regioselectivity making the process unprofitable and unsustainable. By contrast, the use of a recombinant E. coli system has recently shown high suitability and efficiency. In this study, we aim to overcome limitations in this biotechnological medrane conversion yielding the essential methylprednisolone-precursor premedrol by optimizing the CYP21A2-based whole-cell system on a laboratory scale. We successfully improved the whole-cell process in terms of premedrol production by (a) improving the electron supply to CYP21A2; here we use the N-terminally truncated version of the bovine NADPH-dependent cytochrome P450 reductase (bCPR-27 ) and coexpression of microsomal cytochrome b5 ; (b) enhancing substrate access to the heme by modification of the CYP21A2 substrate access channel; and (c) circumventing substrate inhibition which is presumed to be the main limiting factor of the presented system by developing an improved fed-batch protocol. By overcoming the presented limitations in whole-cell biotransformation, we were able to achieve a more than 100% improvement over the next best system under equal conditions resulting in 691 mg·L-1 ·d-1 premedrol.


Assuntos
Escherichia coli/genética , Engenharia Metabólica/métodos , Metilprednisolona , Proteínas Recombinantes/metabolismo , Esteroide 21-Hidroxilase/metabolismo , Animais , Biotransformação , Bovinos , Escherichia coli/metabolismo , Hidroxilação , Metilprednisolona/análogos & derivados , Metilprednisolona/análise , Metilprednisolona/química , Metilprednisolona/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Esteroide 21-Hidroxilase/química , Esteroide 21-Hidroxilase/genética
4.
J Drugs Dermatol ; 19(9): 894-896, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33026750

RESUMO

Epidermal growth factor (EGFR)-inhibitors have emerged as the primary therapy in advanced solid tumor malignancies because of improvement in survival with overall favorable side effect profile. However, 50–90% of patients treated with EGFR-inhibitors develop a follicular or acneiform rash, which can be symptomatic and source of psychosocial distress, negatively impacting quality of life. As this acneiform rash is a well-recognized cutaneous toxicity of EGFR-inhibitors, a treatment algorithm has been proposed for management based on severity. However, treatment options for EGFR-inhibitor induced rash may not be generalizable to African Americans whose differences in skin biology and sensitivity present pathophysiologic challenges. Herein, we present a case of an African American patient who developed this acneiform rash while on cetuximab. We also review the few cases that have been reported in the literature of EGFR-inhibitor rash in African Americans, highlighting important management considerations in this patient population. J Drugs Dermatol. 2020;19(9):894-896. doi:10.36849/JDD.2020.5275.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Cetuximab/efeitos adversos , Toxidermias/imunologia , Neoplasias Orofaríngeas/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Negro ou Afro-Americano , Antibacterianos/uso terapêutico , Toxidermias/diagnóstico , Toxidermias/tratamento farmacológico , Toxidermias/etnologia , Quimioterapia Combinada , Receptores ErbB/antagonistas & inibidores , Humanos , Masculino , Metilprednisolona/análogos & derivados , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/imunologia , Neoplasias Orofaríngeas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundário , Resultado do Tratamento
5.
Lancet ; 392(10156): 1423-1433, 2018 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-30343858

RESUMO

BACKGROUND: To our knowledge, the comparative effectiveness of commonly used conservative treatments for carpal tunnel syndrome has not been evaluated previously in primary care. We aimed to compare the clinical and cost-effectiveness of night splints with a corticosteroid injection with regards to reducing symptoms and improving hand function in patients with mild or moderate carpal tunnel syndrome. METHODS: We did this randomised, open-label, pragmatic trial in adults (≥18 years) with mild or moderate carpal tunnel syndrome recruited from 25 primary and community musculoskeletal clinics and services. Patients with a new episode of idiopathic mild or moderate carpal tunnel syndrome of at least 6 weeks' duration were eligible. We randomly assigned (1:1) patients (permutated blocks of two and four by site) with an online web or third party telephone service to receive either a single injection of 20 mg methylprednisolone acetate (from 40 mg/mL) or a night-resting splint to be worn for 6 weeks. Patients and clinicians could not be masked to the intervention. The primary outcome was the overall score of the Boston Carpal Tunnel Questionnaire (BCTQ) at 6 weeks. We used intention-to-treat analysis, with multiple imputation for missing data, which was concealed to treatment group allocation. The trial is registered with the European Clinical Trials Database, number 2013-001435-48, and ClinicalTrial.gov, number NCT02038452. FINDINGS: Between April 17, 2014, and Dec 31, 2016, 234 participants were randomly assigned (118 to the night splint group and 116 to the corticosteroid injection group), of whom 212 (91%) completed the BCTQ at 6 weeks. The BCTQ score was significantly better at 6 weeks in the corticosteroid injection group (mean 2·02 [SD 0·81]) than the night splint group (2·29 [0·75]; adjusted mean difference -0·32; 95% CI -0·48 to -0·16; p=0·0001). No adverse events were reported. INTERPRETATION: A single corticosteroid injection shows superior clinical effectiveness at 6 weeks compared with night-resting splints, making it the treatment of choice for rapid symptom response in mild or moderate carpal tunnel syndrome presenting in primary care. FUNDING: Arthritis Research UK.


Assuntos
Anti-Inflamatórios/administração & dosagem , Síndrome do Túnel Carpal/terapia , Injeções , Metilprednisolona/análogos & derivados , Contenções , Adulto , Idoso , Síndrome do Túnel Carpal/economia , Análise Custo-Benefício , Feminino , Humanos , Masculino , Metilprednisolona/administração & dosagem , Acetato de Metilprednisolona , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do Tratamento
6.
Pediatr Dermatol ; 36(6): 1017-1018, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31602682

RESUMO

The vast majority of atopic dermatitis follows a mild, chronic relapsing course. In this article, we highlight the art and practice of treating atopic dermatitis based upon a foundation of maintenance care and a ladder of therapy that can teach patients and their families how to best tailor their pharmaceutical options to optimize the management of their disease.


Assuntos
Dermatite Atópica/tratamento farmacológico , Índice de Gravidade de Doença , Clobetasol/uso terapêutico , Gerenciamento Clínico , Esquema de Medicação , Glucocorticoides/uso terapêutico , Humanos , Metilprednisolona/análogos & derivados , Metilprednisolona/uso terapêutico , Inibidores da Fosfodiesterase 4/uso terapêutico , Triancinolona/uso terapêutico
7.
Contact Dermatitis ; 78(1): 76-82, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28960334

RESUMO

BACKGROUND: Corticosteroids are among the most commonly used topical drugs. Contact allergy to these exists, but can be easily missed. Corticosteroid screening markers have been included in the baseline series with the aim of detecting most of the sensitized patients. OBJECTIVES: To assess the prevalence of contact allergy to topical corticosteroids in Spain and examine the usefulness of corticosteroid markers to detect contact allergy to corticosteroids. METHODS: In total, 3699 patients referred to 20 dermatology departments across Spain for patch testing with the baseline series, including budesonide and tixocortol pivalate, were also tested with six supplementary corticosteroids (methylprednisolone aceponate, mometasone furoate, prednicarbate, clobetasol propionate, betamethasone 17-valerate, and betamethasone 17,21-dipropionate). Additionally, 2547 (68.8%) patients were tested with hydrocortisone 17-butyrate. RESULTS: Fifty-four patients showed positive reactions to at least one of all tested corticosteroids (1.46%). Thirty-nine (1.05%) reacted to at least one of the additionally tested corticosteroids; among these, 24 of 39 (61.5%) did not react to any of the corticosteroid allergy screening markers tested. CONCLUSIONS: More than half of the patients who were allergic to the additionally tested corticosteroids were not detected with the corticosteroid allergy markers. An update of the corticosteroid allergy screening markers is encouraged, with consideration of group 3 corticosteroids.


Assuntos
Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/epidemiologia , Fármacos Dermatológicos/efeitos adversos , Testes do Emplastro , Administração Cutânea , Adulto , Betametasona/administração & dosagem , Betametasona/efeitos adversos , Betametasona/análogos & derivados , Valerato de Betametasona/administração & dosagem , Valerato de Betametasona/efeitos adversos , Clobetasol/administração & dosagem , Clobetasol/efeitos adversos , Dermatite Alérgica de Contato/etiologia , Fármacos Dermatológicos/administração & dosagem , Feminino , Humanos , Hidrocortisona/administração & dosagem , Hidrocortisona/efeitos adversos , Hidrocortisona/análogos & derivados , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Metilprednisolona/análogos & derivados , Furoato de Mometasona/administração & dosagem , Furoato de Mometasona/efeitos adversos , Valor Preditivo dos Testes , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Prednisolona/análogos & derivados , Prevalência , Estudos Prospectivos , Espanha/epidemiologia
8.
Int Orthop ; 42(1): 109-116, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29119296

RESUMO

INTRODUCTION: Plantar fasciitis is a common cause of heel pain. Considering different interventions which are applied for patients with plantar fasciitis, dry needling is proposed as a new modality of treatment recently. The aim of this study is to evaluate the effectiveness of dry needling versus steroid injection for plantar fasciitis. METHODS: Sixty-six patients were recruited to this single-blind clinical trial study. Participants were randomly allocated to receive 1 ml (40 mg) of Depo-Medrol (methylprednisolone acetate) or dry needling. They were followed up for 12 months and monitored for total perception of pain using the visual analogue scale (VAS), with data obtained in baseline and at three weeks, six weeks, three months, six months and one year after treatment. RESULTS: Mean VAS score before treatment was 6.96 ± 0.87 for the steroid group and 6.41 ± 0.83 for the dry-needling group (P value = 0.54). Steroid injection reduced VAS scores rapidly until three weeks after treatment compared with dry needling (0.32 ± 0.71 and 3.47 ± 1.32, respectively; P value < 0.001). However, patients who were underwent dry needling reported lower VAS scores at the end of follow-up compared with the steroid group (0.69 ± 0.93 and 2.09 ± 1.58, respectively; P value = 0.004). Over the long term, 82.3% and 17.6% of changes in pain were contributed to time since treatment and treatment method, respectively (P values < 0.001). CONCLUSIONS: Steroid injection can palliate plantar heel pain rapidly but dry needling can provide more satisfactory results for patients with plantar fasciitis in the long term.


Assuntos
Analgesia por Acupuntura/métodos , Fasciíte Plantar/terapia , Glucocorticoides/administração & dosagem , Metilprednisolona/análogos & derivados , Adulto , Feminino , Seguimentos , Humanos , Masculino , Metilprednisolona/administração & dosagem , Acetato de Metilprednisolona , Pessoa de Meia-Idade , Dor/etiologia , Manejo da Dor/métodos , Medição da Dor/métodos , Método Simples-Cego , Resultado do Tratamento
9.
J Dtsch Dermatol Ges ; 16(1): 34-40, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29280553

RESUMO

BACKGROUND: The sulfone dapsone has an established role in systemic therapy. Its pharmacological and toxicological properties are well known. Topically, dapsone is used in a gel formulation for the treatment of acne vulgaris. In addition, there have been individual case reports on the efficacy of topical dapsone preparations in the treatment of various neutrophilic dermatoses. To date, no finished medicinal product for topical use has been available in Germany. MATERIAL AND METHODS: Against this background, we set out to develop extemporaneous preparations containing dapsone (5 %) that meet the quality requirements of the European Pharmacopoeia as well as the manufacturing requirements of the German Ordinance on the Operation of Pharmacies (ApBetrO). These formulations included the incorporation of dapsone in a hydrophobic cream base ("hydrophobe Basiscreme DAC") as well as in methylprednisolone aceponate 0.1 % ointment (alternatively, in the latter's cream base without active ingredient). RESULTS: Tests aimed at investigating the physical, chemical, and microbiological stability of these formulations showed them to meet the aforementioned quality requirements. CONCLUSION: The extemporaneous formulations presented herein broaden the therapeutic options for topical treatment, in particular for patients with chronic inflammatory dermatoses associated with a neutrophilic pathogenesis.


Assuntos
Dapsona/química , Dapsona/uso terapêutico , Administração Cutânea , Combinação de Medicamentos , Composição de Medicamentos , Estabilidade de Medicamentos , Humanos , Metilprednisolona/análogos & derivados , Metilprednisolona/química , Metilprednisolona/uso terapêutico , Pomadas , Creme para a Pele
10.
J Cell Biochem ; 118(8): 2072-2086, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27918081

RESUMO

Steroid, also known as glucocorticoid, induced osteonecrosis of the femoral head in young adults, which has been a challenging disorder for the frequent incidence of collapse of femoral head, leading to dysfunction of hip joint and impairing life quality of human. Bioavailable and less toxic synthetic retinoids, such as the atypical adamantyl retinoid ST1926, have been developed and investigated in clinical trials for many diseases. Serum lipid-related indicators were assessed to elucidate the role of ST1926 in regulating lipid metabolism. Microfocal computed tomography (Micro-CT) was included to explore the effects of ST1926 treatment on microstructure and bone mass. Then, the role of ST1926 treatment in regulating osteoclast differentiation was also evaluated in vivo and in vitro. In addition, alkaline phosphatase (ALP), osteoprotegerin (OPG), bone alkaline phosphatase (BAP) and bone morphogenic protein (BMP) expression in serum and cells were detected at protein or mRNA levels. The ratio of empty lacuna in the bone tissue samples was significantly low in ST1926-treated groups than in the control group. Micro-CT evaluation suggested that ST1926 treatment could ameliorate the microstructure of the bone and up-regulate bone mineral density in steroid-induced rats. Moreover, ST1926 treatment suppressed osteoclast differentiation and promoted bone formation markers. Also, OPG, ALP, and Wnt3a/ß-catenin down-regulation as well as inflammation up-regulation could be reversed by ST1926 administration through NFκB inhibition. Hence, ST1926 may inhibit steroid-induced osteoporosis and promote steroid-induced bone remodeling by regulating the Wnt3a/ß-catenin/NFκB signaling pathway. J. Cell. Biochem. 118: 2072-2086, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Adamantano/análogos & derivados , Conservadores da Densidade Óssea/farmacologia , Reabsorção Óssea/prevenção & controle , Cinamatos/farmacologia , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Osteonecrose/tratamento farmacológico , Adamantano/farmacologia , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Densidade Óssea/efeitos dos fármacos , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Reabsorção Óssea/induzido quimicamente , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Regulação da Expressão Gênica , Masculino , Metilprednisolona/efeitos adversos , Metilprednisolona/análogos & derivados , Acetato de Metilprednisolona , NF-kappa B/genética , NF-kappa B/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteonecrose/induzido quimicamente , Osteonecrose/genética , Osteonecrose/metabolismo , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais , Proteína Wnt3A/genética , Proteína Wnt3A/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
11.
Inflamm Res ; 66(3): 239-248, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27853846

RESUMO

OBJECTIVE AND DESIGN: To determine the ability of methylprednisolone acetate (MPA) to influence interleukin 1ß (IL1ß)-induced gene expression in ovine knee joint tissues. MATERIAL OR SUBJECTS: Ovine articular cartilage, synovium, and infrapatellar fat pad (IPFP) explants. TREATMENT: Explants were treated with 10-3 M or 10-4 M MPA. METHODS: Explant treatment groups: (1) control (DMEM); (2) inflammation (IL1ß); (3) IL1ß + 10-3 M MPA; or (4) IL1ß + 10-4 M MPA. Cell viability was assessed pre- and post-treatment. Expression of mRNA levels for inflammatory, degradative, anabolic, innate immunity, and adipose-related molecules was quantified via qPCR, and analyzed via the comparative C T method. RESULTS: Except for IL8 in a subset of cartilage locations, matrix metalloproteinases (MMPs) were the only genes consistently affected by MPA. MPA mitigated IL1ß-induced MMP3 expression levels in all regions of the articular cartilage, and in the synovium and IPFP, while MMP1 mRNA expression levels were significantly decreased with MPA after IL1ß in the tibial plateau and synovium, but paradoxical increases in the IPFP. MMP13 mRNA expression levels exhibited significant decreases with MPA after IL1ß in the femoral condyles, tibial plateau, synovium, and IPFP. CONCLUSIONS: MPA treatment suppressed IL1ß-induced mRNA levels for MMPs in articular cartilage, synovium, and IPFP and was found to be tissue-, location-, and gene-specific.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Cartilagem Articular/efeitos dos fármacos , Citocinas/genética , Metilprednisolona/análogos & derivados , RNA Mensageiro/metabolismo , Membrana Sinovial/efeitos dos fármacos , Adiponectina/genética , Tecido Adiposo/metabolismo , Animais , Cartilagem Articular/metabolismo , Feminino , Inflamação/metabolismo , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/metabolismo , Leptina/genética , Metaloproteinases da Matriz/genética , Metilprednisolona/farmacologia , Acetato de Metilprednisolona , Nicotinamida Fosforribosiltransferase/genética , Ovinos , Membrana Sinovial/metabolismo , Receptor 4 Toll-Like/genética
12.
Cochrane Database Syst Rev ; 2: CD010847, 2017 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-28158933

RESUMO

BACKGROUND: Simple bone cysts, also known as a unicameral bone cysts or solitary bone cysts, are the most common type of benign bone lesion in growing children. Cysts may lead to repeated pathological fracture (fracture that occurs in an area of bone weakened by a disease process). Occasionally, these fractures may result in symptomatic malunion. The main goals of treatment are to decrease the risk of pathological fracture, enhance cyst healing and resolve pain. Despite the numerous treatment methods that have been used for simple bone cysts in long bones of children, there is no consensus on the best procedure. This is an update of a Cochrane review first published in 2014. OBJECTIVES: To assess the effects (benefits and harms) of interventions for treating simple bone cysts in the long bones of children, including adolescents.We intended the following main comparisons: invasive (e.g. injections, curettage, surgical fixation) versus non-invasive interventions (e.g. observation, plaster cast, restricted activity); different categories of invasive interventions (i.e. injections, curettage, drilling holes and decompression, surgical fixation and continued decompression); different variations of each category of invasive intervention (e.g. different injection substances: autologous bone marrow versus steroid). SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, the China National Knowledge Infrastructure Platform, trial registers, conference proceedings and reference lists. Date of last search: April 2016. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials evaluating methods for treating simple bone cysts in the long bones of children. DATA COLLECTION AND ANALYSIS: Two review authors independently screened search results and performed study selection. We resolved differences in opinion between review authors by discussion and by consulting a third review author. Two review authors independently assessed risk of bias and data extraction. We summarised data using risk ratios (RRs) or mean differences (MDs), as appropriate, and 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the overall quality of the evidence. MAIN RESULTS: In this update in 2017, we did not identify any new randomised controlled trials (RCT) for inclusion. We identified one ongoing trial that we are likely to include in a future update. Accordingly, our results are unchanged. The only included trial is a multicentre RCT conducted at 24 locations in North America and India that compared bone marrow injection with steroid (methylprednisolone acetate) injection for treating simple bone cysts. Up to three injections were planned for participants in each group. The trial involved 90 children (mean age 9.5 years) and presented results for 77 children at two-year follow-up. Although the trial had secure allocation concealment, it was at high risk of performance bias and from major imbalances in baseline characteristics. Reflecting these study limitations, we downgraded the quality of evidence by two levels to 'low' for most outcomes, meaning that we are unsure about the estimates of effect. For outcomes where there was serious imprecision, we downgraded the quality of evidence by a further level to 'very low'.The trial provided very low quality evidence that fewer children in the bone marrow injection group had radiographically assessed healing of bone cysts at two years than in the steroid injection group (9/39 versus 16/38; RR 0.55 favouring steroid injection, 95% CI 0.28 to 1.09). However, the result was uncertain and may be compatible with no difference or small benefit favouring bone marrow injection. Based on an illustrative success rate of 421 children with healed bone cysts per 1000 children treated with steroid injections, this equates to 189 fewer (95% CI 303 fewer to 38 more) children with healed bone cysts per 1000 children treated with bone marrow injections. There was low quality evidence of a lack of difference between the two interventions at two years in functional outcome, based on the Activity Scale for Kids function score (0 to 100; higher scores equate to better outcome: MD -0.90; 95% CI -4.26 to 2.46) or in pain assessed using the Oucher pain score. There was very low quality evidence of a lack of differences between the two interventions for adverse events: subsequent pathological fracture (9/39 versus 11/38; RR 0.80, 95% CI 0.37 to 1.70) or superficial infection (two cases in the bone marrow group). Recurrence of bone cyst, unacceptable malunion, return to normal activities, and participant satisfaction were not reported. AUTHORS' CONCLUSIONS: The available evidence is insufficient to determine the relative effects of bone marrow versus steroid injections, although the bone marrow injections are more invasive. Noteably, the rate of radiographically assessed healing of the bone cyst at two years was well under 50% for both interventions. Overall, there is a lack of evidence to determine the best method for treating simple bone cysts in the long bones of children. Further RCTs of sufficient size and quality are needed to guide clinical practice.


Assuntos
Cistos Ósseos/terapia , Transplante de Medula Óssea/métodos , Glucocorticoides/administração & dosagem , Metilprednisolona/análogos & derivados , Adolescente , Criança , Humanos , Metilprednisolona/administração & dosagem , Acetato de Metilprednisolona , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Acta Radiol ; 58(8): 964-970, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27856801

RESUMO

Background Ultrasound-guided percutaneous irrigation of calcific tendinopathy (US-PICT) with intrabursal steroid injection is an elective treatment for painful rotator cuff calcific tendinopathy. Purpose To compare the efficacy of post-US-PICT intrabursal 40 mg injection of triamcinolone acetonide (TA) versus methylprednisolone acetate (MA). Material and Methods Forty patients (22 women; mean age 48.7 ± 7.2 years) with painful shoulder calcific tendinopathy, treated with TA or MA injected intrabursally after US-PICT, were included in this randomized controlled trial. At baseline and after 1, 7, 15, 30, 45, and 180 days, patients underwent US and clinical examination, using Constant (CS) and VAS (VS) scores. Complications and analgesic use were also recorded. Results Compared to baseline, at the 45-day follow-up, TA and MA group showed a similar improvement (Δ) in CS (42 ± 10 versus 36 ± 9 points) and VS (-4.4 ± 1.3 versus -3.6 ± 1.3 points). At the 180-day follow-up, the improvement was higher in TA versus MA (ΔCS: 53 ± 7 versus 44 ± 7 points; ΔVS: -4.9 ± 1.1 versus -3.9 ± 1 points). Multivariate analysis showed a mean CS higher ( P = 0.02) in TA versus MA group, while VS was similar. TA had a 5 × higher ( P = 0.007) chance of reaching complete remission (CS = 100 points) than MA group. A progressive decrease in analgesic use, concomitant to a significant and similar reduction of bursitis and calcifications, was observed in both groups. No major complications occurred. Conclusion Two-needle US-PICT with intrabursal steroid injection is safe and effective. The chance of reaching better scores and, even more important for a clinical perspective, of functional recovery, is higher in patients treated with TA than MA.


Assuntos
Calcinose/tratamento farmacológico , Glucocorticoides/uso terapêutico , Metilprednisolona/análogos & derivados , Dor de Ombro/tratamento farmacológico , Tendinopatia/tratamento farmacológico , Triancinolona/uso terapêutico , Ultrassonografia de Intervenção , Calcinose/diagnóstico por imagem , Feminino , Glucocorticoides/administração & dosagem , Humanos , Injeções Intralesionais , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Acetato de Metilprednisolona , Pessoa de Meia-Idade , Dor de Ombro/diagnóstico por imagem , Tendinopatia/diagnóstico por imagem , Resultado do Tratamento , Triancinolona/administração & dosagem
14.
J Shoulder Elbow Surg ; 26(10): 1789-1793, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28689827

RESUMO

BACKGROUND: Arthroscopic rotator cuff (RC) repair incorporates suture anchors to secure torn RC tendons to the greater tuberosity (GT) bone. RC repair strength depends on the anchor-bone interface and on the quality of the GT. We evaluated the effect of single and multiple corticosteroid injections on the pullout strength of suture anchors. METHODS: Fifty rats were divided into those receiving saline solution injection (control group), a single methylprednisolone acetate (MTA) injection (MTA1 group), or 3 once-weekly MTA injections (MTA3 group). Rats were killed humanely at 1 or 4 weeks after the last injection. A mini-suture anchor was inserted into the humeral head through the GT. Specimens were tested biomechanically. RESULTS: At 1 week after the last injection, the mean maximal pullout strength was significantly reduced in the MTA1 group (63.5%) and MTA3 group (56%) compared with the control group (P < .05 for both). Mean stiffness decreased significantly in both treatment groups compared with controls (P < .05). At 4 weeks after the last injection, there was a significant increase in the mean maximal pullout strength after single and triple MTA injections compared with values recorded at the 1-week time point (P < .05). At 4 weeks, the mean maximal pullout strength after a single MTA injection was 92.8% of the pullout strength measured in the control group. CONCLUSIONS: We showed a significant detrimental effect of corticosteroid exposure on the pullout strength of a suture anchor at 1 week. However, this effect was transient and resolved within a relatively short period. These findings indicate that a waiting period is required between subacromial corticosteroid injection and RC repair surgery that involves the use of suture anchors.


Assuntos
Anti-Inflamatórios/uso terapêutico , Artroscopia , Cabeça do Úmero/cirurgia , Metilprednisolona/análogos & derivados , Manguito Rotador/cirurgia , Âncoras de Sutura , Animais , Artroplastia , Fenômenos Biomecânicos , Metilprednisolona/uso terapêutico , Acetato de Metilprednisolona , Ratos , Técnicas de Sutura , Tendões/cirurgia , Resistência à Tração
15.
Vet Dermatol ; 28(5): 499-e117, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28378419

RESUMO

BACKGROUND: Pemphigus foliaceus is a severe, autoimmune blistering skin disease, which is described in humans and some animal species. In small ruminants pemphigus foliaceus has rarely been described and, to the best of the authors' knowledge, little information is available about successful treatment in sheep. AIM: This case report describes a Berrichon du Cher ram with the presumed diagnosis of pemphigus foliaceus. METHODS: The ram was treated with methylprednisolone acetate 40 mg at a dosage of 2.5 mg/kg in one subcuticular injection at four week intervals over a one year period, with regular observation of clinical parameters. Four months after treatment was initiated the haematological parameters showed lymphopenia and leukopenia; some enzyme activities were substantially increased. RESULTS: The ram's dermatological condition improved to the point of complete healing of the affected skin. The ram was discharged in good condition. No adverse effects, except an elevation of some enzymes associated with liver function, were observed. At postmortem examination moderate fatty liver syndrome was the only abnormality found. CONCLUSIONS AND CLINICAL IMPORTANCE: This case report demonstrated that long term therapy with methylprednisolone acetate in a sheep with pemphigus foliaceus did not have a negative effect on clinical parameters. Nevertheless, due to the extended statutory withdrawal period resulting from the regular administration of glucocorticoids, such a therapeutic option must be critically assessed in food producing animals.


Assuntos
Anti-Inflamatórios/uso terapêutico , Metilprednisolona/análogos & derivados , Pênfigo/veterinária , Doenças dos Ovinos/tratamento farmacológico , Animais , Anti-Inflamatórios/administração & dosagem , Esquema de Medicação/veterinária , Injeções Subcutâneas/veterinária , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Acetato de Metilprednisolona , Pênfigo/diagnóstico , Pênfigo/tratamento farmacológico , Pênfigo/patologia , Ovinos , Doenças dos Ovinos/diagnóstico , Doenças dos Ovinos/patologia , Pele/patologia
16.
Hautarzt ; 68(4): 307-315, 2017 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-28091698

RESUMO

The combination of topical fungicide and glucocorticoids has been proven as a successful therapy of cutaneous mycoses with accompanying inflammatory reactions, particularly when used at an early stage. Various national and international therapeutic guidelines recommend this practice. In this context, two individually manufactured formulations have been developed and tested for stability: the combination of methylprednisolone aceponate-a topical glucocorticoid with the therapeutic index of 2.0-with clotrimazole and with ciclopirox olamine, respectively. This has been conducted in compliance with the requirements for quality controlled extemporaneous formulations and the legal framework of the German Pharmacy Working Regulations (Apothekenbetriebsordnung). There are now two formulations for clinical use that are microbiologically, physically, and chemically stable, which combine methylprednisolone aceponate-a glucocorticoid with a good risk-benefit ratio-with the broad-spectrum fungicides clotrimazole and, for the first time, ciclopirox olamine.


Assuntos
Antifúngicos/administração & dosagem , Clotrimazol/administração & dosagem , Dermatomicoses/tratamento farmacológico , Dermatomicoses/patologia , Metilprednisolona/análogos & derivados , Piridonas/administração & dosagem , Administração Tópica , Ciclopirox , Fármacos Dermatológicos/administração & dosagem , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Medicina Baseada em Evidências , Humanos , Metilprednisolona/administração & dosagem , Resultado do Tratamento
17.
Clin Exp Rheumatol ; 34(5): 857-863, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27244700

RESUMO

OBJECTIVES: The aim of the present study was to compare the clinical results and the quality of life in patients with symptomatic knee osteoarthritis randomised to either a new HA (HYADD 4) or corticosteroid (CS). A separate rationale was to evaluate the safety profile of HYADD 4. METHODS: All the patients presenting for unilateral symptomatic primary knee osteoarthritis were prospectively randomly assigned to receive 2 injections of either HYADD 4 or CS, and were evaluated before the injections and at 6, 12, 26 and 52 weeks. Primary end point was WOMAC score at 26 weeks; secondary end points were WOMAC score, VAS for pain, and SF-36 score at any time point. RESULTS: There were 53 females and 22 males in the HYADD 4 group (mean age 71.5±10.6 years), and 50 females and 25 males in the CS group (mean age 68.6±9.9 years). The observed sided effects were mild and their incidence was similar in the two groups. Patients in the HYADD 4 group reported significantly better WOMAC scores at 26 weeks. The patients improved in all considered outcomes after the injections, with a peak of therapeutic effect between 6 and 12 weeks. Patients in the HYADD 4 group obtained significantly better scores than the CS group up to 26 weeks. At the 1-year follow-up no statistically significant differences between treatments were detected. CONCLUSIONS: HYADD 4 did not have significantly higher side effects when compared to CS injections and provided better short-term (but not long-term) control of symptoms in patients with mild to moderate knee osteoarthritis. Patients with less pain and dysfunction at baseline may be the best candidates for HYADD 4 injections.


Assuntos
Antirreumáticos/uso terapêutico , Glucocorticoides/uso terapêutico , Ácido Hialurônico/uso terapêutico , Articulação do Joelho/efeitos dos fármacos , Metilprednisolona/análogos & derivados , Osteoartrite do Joelho/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Avaliação da Deficiência , Esquema de Medicação , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Nível de Saúde , Indicadores Básicos de Saúde , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/efeitos adversos , Ácido Hialurônico/análogos & derivados , Injeções Intra-Articulares , Articulação do Joelho/fisiopatologia , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Metilprednisolona/uso terapêutico , Acetato de Metilprednisolona , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/fisiopatologia , Osteoartrite do Joelho/psicologia , Medição da Dor , Estudos Prospectivos , Qualidade de Vida , Indução de Remissão , Cidade de Roma , Índice de Gravidade de Doença , Método Simples-Cego , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
18.
J Biol Regul Homeost Agents ; 30(2 Suppl 3): 77-81, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27498662

RESUMO

As one of the most common dermatologic chronic-recurrent disease, variable therapeutic options are available today for management of psoriasis. Although topical high potency corticosteroids, alone or in association with salicylic acid or vitamin D analogues, are still considered the best treatment, they do not seem to possess the capability for a long-term control of the disease or prevent recurrences, as their side effects are major contraindications for continuative use. The aim of this study was to investigate whether Dr. Michaels® product family is comparable to methylprednisolone aceponate (MPA) as a viable alternative treatment option for the treatment and management of stable chronic plaque psoriasis. Thirty adults (13 male, 17 female, mean age 40 years) with mild to severe stable chronic plaque psoriasis, were included in the study. Patients were advised to treat the lesions of the two sides of their body (left and right) with two different unknown modalities for 8 weeks; the pack of Dr. Michaels® products on the left side (consisting of a cleansing gel, an ointment and a skin conditioner) and a placebo pack on the right side, consisting of a cleansing gel, methylprednisolone ointment and a placebo conditioner. Assessment was done using the Psoriasis Activity Severity Index (PASI) scores before treatment and after 2, 4, 6 and 8 weeks. The results achieved with the Dr. Michaels® (Soratinex®) product family for the treatment of chronic plaque psoriasis were better than the results achieved with methylprednisolone aceponate (MPA), even though quicker resolution was achieved with the steroid with 45% of patients achieving resolution within 8-10 days in comparison to 5-6 weeks in the Dr. Michaels® (Soratinex®) group. Before therapy, the mean PASI score of the LHS in Dr. Michaels® (Soratinex®) group was 13.8±4.1 SD and 14.2±4.2 SD in the RHS methylprednisolone aceponate (MPA) group. After 8 weeks of treatment 62% of the Dr. Michaels® (Soratinex®) group had achieved resolution whilst in the methylprednisolone aceponate (MPA) group, the figure remained at 45%. The mean PASI score after 8 weeks of treatment was calculated and in the LHS Dr. Michaels® (Soratinex®) group it was 2.8±1.6 SD and 6.8±2.4 SD in the RHS methylprednisolone aceponate group. In the RHS -methylprednisolone aceponate (MPA) group, 22% of patients failed to respond to the treatment in comparison to 6% in the LHS Dr. Michaels® (Soratinex®) group. Based on the results of this study, Dr. Michaels® products are a more effective treatment option, with insignificant side effects, compared to local treatment with methylprednisolone aceponate (MPA).


Assuntos
Fármacos Dermatológicos/uso terapêutico , Metilprednisolona/análogos & derivados , Psoríase/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Metilprednisolona/uso terapêutico , Psoríase/patologia , Pele/efeitos dos fármacos , Pele/patologia , Resultado do Tratamento
19.
Dig Dis Sci ; 61(2): 572-7, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26320087

RESUMO

BACKGROUND: Abdominal wall pain (AWP) is an important cause of chronic abdominal pain. History and physical examination are critical to the diagnosis of AWP. Trigger point injection (TPI) using either a steroid or a local anesthetic or a combination of both is often used to treat AWP. AIM: To determine the efficacy of ultrasound-guided TPI and to determine the predictors of a successful response. METHODS: Patients who received ultrasound-guided TPI between July 2010 and June 2011 were surveyed. The primary outcome was determined using the Treatment Efficacy Questionnaire (TEQ). Electronic medical records were reviewed to determine patient, pain and TPI characteristics. Linear regression was used to determine the predictors of a successful response on the TEQ. RESULTS: Right upper quadrant was the most common site of AWP, and the median pain duration was 12 months. Pain was rated as >8 (1-10 scale) by 57 % and 30 % described it as an ache. Narcotic use was reported in 38 %, and 73 % had a history of at least one abdominal surgery. Forty-four of the 120 (37 %) patients met the criteria for responder on the TEQ. Compared to before treatment, 36 % reported being "significantly better" and 22 % "slightly better." Multiple linear regression analysis showed that higher somatization negatively predicted response. None of the other historical, examination or TPI characteristics were associated with response to the TPI. CONCLUSION: TPI can provide significant, long-term symptom relief in a third of patients with chronic abdominal pain attributed to AWP. Somatization was inversely related to the treatment success.


Assuntos
Dor Abdominal/tratamento farmacológico , Parede Abdominal , Bupivacaína/farmacologia , Lidocaína/farmacologia , Metilprednisolona/análogos & derivados , Pontos-Gatilho/patologia , Betametasona/administração & dosagem , Betametasona/farmacologia , Bupivacaína/administração & dosagem , Feminino , Humanos , Lidocaína/administração & dosagem , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/farmacologia , Acetato de Metilprednisolona , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
BMC Musculoskelet Disord ; 17(1): 415, 2016 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-27716159

RESUMO

BACKGROUND: Patients diagnosed with idiopathic mild to moderate carpal tunnel syndrome (CTS) are usually managed in primary care and commonly treated with night splints and/or corticosteroid injection. The comparative effectiveness of these interventions has not been reliably established nor investigated in the medium and long term. The primary objective of this trial is to investigate whether corticosteroid injection is effective in reducing symptoms and improving hand function in mild to moderate CTS over 6 weeks when compared with night splints. Secondary objectives are to determine specified comparative clinical outcomes and cost effectiveness of corticosteroid injection over 6 and 24 months. METHOD/DESIGN: A multicentre, randomised, parallel group, clinical pragmatic trial will recruit 240 adults aged ≥18 years with mild to moderate CTS from GP Practices and Primary-Secondary Care Musculoskeletal Interface Clinics. Diagnosis will be by standardised clinical assessment. Participants will be randomised on an equal basis to receive either one injection of 20 mg Depo-Medrone or a night splint to be worn for 6 weeks. The primary outcome is the overall score of the Boston Carpal Tunnel Questionnaire (BCTQ) at 6 weeks. Secondary outcomes are the BCTQ symptom severity and function status subscales, symptom intensity, interrupted sleep, adherence to splinting, perceived benefit and satisfaction with treatment, work absence and reduction in work performance, EQ-5D-5L, referral to surgery and health utilisation costs. Participants will be assessed at baseline and followed up at 6 weeks, 6, 12 and 24 months. The primary analysis will use an intention to treat (ITT) approach and multiple imputation for missing data. The sample size was calculated to detect a 15 % greater improvement in the BTCQ overall score in the injection group compared to night-splinting at approximately 90 % power, 5 % two-tailed significance and allows for 15 % loss to follow-up. DISCUSSION: The trial makes an important contribution to the evidence base available to support effective conservative management of CTS in primary care. No previous trials have directly compared these treatments for CTS in primary care populations, reported on clinical effectiveness at more than 6 months nor compared cost effectiveness of the interventions. TRIAL REGISTRATION: Trial registration: EudraCT 2013-001435-48 (registered 05/06/2013), ClinicalTrials.gov NCT02038452 (registered 16/1/2014), and Current Controlled Trials ISRCTN09392969 (retrospectively registered 01/05/2014).


Assuntos
Síndrome do Túnel Carpal/terapia , Análise Custo-Benefício , Glucocorticoides/uso terapêutico , Metilprednisolona/análogos & derivados , Contenções/economia , Adulto , Síndrome do Túnel Carpal/economia , Glucocorticoides/administração & dosagem , Glucocorticoides/economia , Mãos , Humanos , Injeções , Metilprednisolona/administração & dosagem , Metilprednisolona/economia , Metilprednisolona/uso terapêutico , Acetato de Metilprednisolona , Satisfação do Paciente , Atenção Primária à Saúde/métodos , Inquéritos e Questionários , Resultado do Tratamento
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