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1.
Cesk Slov Oftalmol ; 76(4): 1-15, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33086847

RESUMO

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and uveitis is its most important extra-articular manifestation. Evidence-based recommendations are available only to a limited extent and therefore JIA associated uveitis management is mostly based on physicians experience. Consequently, treatment practices differ widely, both nationally and internationally. Therefore, an effort to optimize and publish recommendations for the care of children and young adults with rheumatic diseases was launched in 2012 as part of the international project SHARE (Single Hub and Access Point for Pediatric Rheumatology in Europe) to facilitate clinical practice for paediatricians and (paediatric) rheumatologists. The aim of this work was to translate published international SHARE recommendations for the diagnosis and treatment of JIA associated uveitis and to adapt them for use in the Czech and Slovak Republics. International recommendations were developed according to the standard methodology of the European League against Rheumatism (EULAR) by a group of nine experienced paediatric rheumatologists and three experts in ophthalmology. It was based on a systematic literature review and evaluated in the form of an online survey and subsequently discussed using a nominal group technique. Recommendations were accepted if > 80% agreement was reached (including all three ophthalmologists). A total of 22 SHARE recommendations were accepted: 3 on diagnosis, 5 on disease activity assessment, 12 on treatment and 2 on future recommendations. Translation of the original text was updated and modified with data specific to the czech and slovak health care systems and supplemented with a proposal for a protocol of ophthalmological dispensarization of paediatric JIA patients and a treatment algorithm for JIA associated uveitis. Conclusion: The aim of the SHARE initiative is to improve and standardize care for paediatric patients with rheumatic diseases across Europe. Therefore, recommendations for the diagnosis and treatment of JIA-associated uveitis have been formulated based on the evidence and agreement of leading European experts in this field.


Assuntos
Artrite Juvenil , Uveíte , Artrite Juvenil/complicações , Artrite Juvenil/diagnóstico , Artrite Juvenil/terapia , Criança , República Tcheca/epidemiologia , Europa (Continente) , Humanos , Eslováquia/epidemiologia , Uveíte/diagnóstico , Uveíte/epidemiologia , Uveíte/etiologia , Adulto Jovem
2.
Pediatr Rheumatol Online J ; 14(1): 36, 2016 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-27301536

RESUMO

BACKGROUND: There is a lack of published evidence on the importance of methotrexate (MTX) dose and route of administration on both its efficacy and adverse events in children with Juvenile Idiopathic Arthritis (JIA). We aimed to document our clinical practice based on the treat-to-target approach in order to support the concept that better therapeutic effect achieved with an optimal dose of parenteral MTX is associated with clinically acceptable adverse effects comparable to those reported for oral treatment. METHODS: Study inclusion criteria were indication of new MTX therapy for active arthritis in confirmed JIA patients younger than 18 years. Eligible patients were evaluated prospectively every 3 months for 1 year using standardized instruments for treatment response (American College of Rheumatology Pediatric (ACRPedi) response, Juvenile Arthritis Disease Activity Score (JADAS) 71, Clinically Inactive Disease (CID)) and adverse events (laboratory monitoring, Methotrexate Intolerance Severity Score (MISS)). MTX responders had to achieve at least ACRPedi 70 response. MTX intolerance was defined by MISS ≥ 6. RESULTS: In 45/55 patients (81.8 %) MTX was started as subcutaneous injection. The initial median weekly dose was 14.4 mg/m(2) in parenteral and 11.7 mg/m(2) in oral administration. MTX therapy was effective in the level of ACRpedi70 and CID in 50.9 % and 30.9 % of patients at month 6 and in 70.9 % and 56.4 % after 12 months of the treatment, respectively. MTX intolerance at 6 and 12 months was noted in 25.5 % and 30.6 %, respectively. Management of intolerance included change in the dose and/or route of administration, education and councelling. Adverse events led to MTX withdrawal in 5 patients (9 %) due to toxicity (n = 3) and intolerance (n = 2). We did not find any significant predictive factors for either MTX therapeutic response or intolerance. CONCLUSION: Subcutaneous MTX weekly dose around 15 mg/m(2) is associated not only with a high response rate within the first 12 months of treatment, but also with a relatively low rate of significant adverse effects that would lead to the treatment termination. It allows early recognition of MTX non-responders and addition of biologic therapy. Sustainability of therapeutic effect and longer-term evolution of adverse events will be addressed by an ongoing extension of the study.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Juvenil/tratamento farmacológico , Artrite Psoriásica/tratamento farmacológico , Metotrexato/administração & dosagem , Dor Abdominal/induzido quimicamente , Administração Oral , Anemia/induzido quimicamente , Antirreumáticos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Subcutâneas , Estimativa de Kaplan-Meier , Masculino , Metotrexato/efeitos adversos , Náusea/induzido quimicamente , Úlceras Orais/induzido quimicamente , Estudos Prospectivos , Resultado do Tratamento , Vômito/induzido quimicamente
3.
Pharmacogenomics J ; 14(4): 356-64, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24709693

RESUMO

Clinical response to methotrexate (MTX) treatment for children with juvenile idiopathic arthritis (JIA) displays considerable heterogeneity. Currently, there are no reliable predictors to identify non-responders: earlier identification could lead to a targeted treatment. We genotyped 759 JIA cases from the UK, the Netherlands and Czech Republic. Clinical variables were measured at baseline and 6 months after start of the treatment. In Phase I analysis, samples were analysed for the association with MTX response using ordinal regression of ACR-pedi categories and linear regression of change in clinical variables, and identified 31 genetic regions (P<0.001). Phase II analysis increased SNP density in the most strongly associated regions, identifying 14 regions (P<1 × 10(-5)): three contain genes of particular biological interest (ZMIZ1, TGIF1 and CFTR). These data suggest a role for novel pathways in MTX response and further investigations within associated regions will help to reach our goal of predicting response to MTX in JIA.


Assuntos
Artrite Juvenil/tratamento farmacológico , Metotrexato/uso terapêutico , Artrite Juvenil/genética , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
4.
Clin Exp Rheumatol ; 27(6): 1047-53, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20149329

RESUMO

OBJECTIVE: To compare the bioavailability of oral and subcutaneous methotrexate (MTX) in children with juvenile idiopathic arthritis (JIA). METHODS: Seventeen JIA patients were administered oral (6.1-22.5 mg/m(2)) or subcutaneous (8.8-28.6 mg/m(2)) MTX. Blood samples were drawn pre-dose, and at 1, 2, and 4 hours after administration. Plasma MTX was determined by high-performance liquid chromatography. Non-compartmental pharmacokinetic analysis included the maximum concentration of plasma MTX (C(max)) and the area under the plasma concentration-time curve in the interval of 0-4h (AUC(0-4h)). RESULTS: The slopes of the regression lines of the dose-corrected parameters Cmax and AUC(0-4h) plotted against the dose were negative for oral administration indicating non-linearity in pharmacokinetics, while they did not differ from zero for subcutaneous MTX. In two groups dosed orally with < or = 10 or >10 mg/m(2) (the average doses: 7.8 vs. 13.8 mg/m(2), p<0.002), the C(max) and AUC(0-4h) were comparable (p > or = 0.32). In four patients switched from oral to subcutaneous administration of the same dose, the bioavailability of oral MTX tended to be 11-15% lower when compared to subcutaneous route. CONCLUSION: The differences in the pharmacokinetic measures of early systemic exposure between oral and subcutaneous routes support the view that lower and saturable intestinal absorption of oral MTX limits its bioavailability and efficacy within the range of standard doses used to treat children with JIA. In light of this evidence it can be recommended to use parenteral route of administration when MTX dose around and above 10-15 mg/m(2) is needed to achieve sufficient response.


Assuntos
Artrite Juvenil/tratamento farmacológico , Metotrexato/administração & dosagem , Metotrexato/farmacocinética , Administração Oral , Antirreumáticos/administração & dosagem , Antirreumáticos/farmacocinética , Área Sob a Curva , Disponibilidade Biológica , Criança , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Subcutâneas , Masculino , Análise de Regressão
5.
Rheumatology (Oxford) ; 45(10): 1273-5, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16595521

RESUMO

OBJECTIVES: To evaluate bone quality by means of quantitative ultrasonometry (QUS) in children with juvenile idiopathic arthritis (JIA). METHODS: Seventy children [37 with oligoarticular JIA, mean age (+/-s.d.) 10.54 +/- 3.42 yr; and 33 with polyarticular rheumatoid factor negative JIA, mean age (+/- s.d.) 11.33 +/- 2.88 yr] were enrolled. Quantitative ultrasonometry was measured on both heels with a Cuba Clinical portable device. Body height, weight and body mass index were recorded together with disease duration and cumulative dose of prednisone. RESULTS: The lowest QUS parameters were observed in children with polyarticular JIA (P< 0.001 and 0.01 when compared with reference data and oligoarticular JIA, respectively). In children with oligoarticular JIA, the QUS values were also significantly lower in comparison with the reference data (P< 0.002). The QUS parameters were strongly influenced by body height, and to a lesser degree by body weight. In children with polyarticular JIA, there were significant inverse correlations between QUS parameters and disease duration [r=-0.57, P< 0.01 for broadband ultrasound attenuation (BUA) and r = - 0.67, P< 0.01 for velocity of sound (VOS)]. Similarly, there were inverse correlations between QUS and cumulative dose of prednisone (r = - 0.48, P< 0.05 for BUA and r =- 0.50, P < 0.01 for VOS, respectively). Similar results were obtained when BUA and VOS were adjusted for height. CONCLUSIONS: Disease duration and cumulative dose of prednisone in children with polyarticular JIA are risk factors of stunted growth and decreased QUS values of bone quality.


Assuntos
Artrite Juvenil/diagnóstico por imagem , Calcâneo/diagnóstico por imagem , Adolescente , Análise de Variância , Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/fisiopatologia , Estatura/efeitos dos fármacos , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Criança , Pré-Escolar , Feminino , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Transtornos do Crescimento/induzido quimicamente , Transtornos do Crescimento/diagnóstico por imagem , Transtornos do Crescimento/fisiopatologia , Humanos , Modelos Lineares , Masculino , Osteoporose/induzido quimicamente , Osteoporose/diagnóstico por imagem , Osteoporose/fisiopatologia , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Estudos Prospectivos , Ultrassonografia
6.
Ann Rheum Dis ; 64(7): 1101-6, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15760930

RESUMO

OBJECTIVE: To prepare a website for families and health professionals containing up to date information about paediatric rheumatic diseases (PRD). METHODS: Firstly, paediatric rheumatology centres and family self help associations were surveyed to characterise current clinical practice of physicians providing care for children with PRD, research activities, and training facilities of each centre. Secondly, international consensus was reached on the content of the website. Finally, the website was developed and the texts translated. RESULTS: The web page contains three main sections: (a) description for families of the characteristics of 15 PRD; (b) list of paediatric rheumatology centres; (c) contact information for family self help associations. A version for 45 countries in 52 languages (with another three in progress) is now available on the web. 291 surveys from 171 centres and 102 family associations were received from 42 countries. The median proportion of time spent in paediatric practice in the centres examined was 100%, with 70% of this time dedicated to paediatric rheumatology. 90% of the centres were willing to perform clinical trials in the future. CONCLUSIONS: The PRINTO/PRES website provides a well defined and competent set of information about PRD, with appropriate multiple translated versions and easy web navigational direction.


Assuntos
Internet , Pediatria/educação , Doenças Reumáticas/psicologia , Reumatologia/educação , Criança , Educação Médica Continuada/métodos , Humanos , Disseminação de Informação , Cooperação Internacional , Educação de Pacientes como Assunto
7.
Rheumatology (Oxford) ; 44(1): 74-9, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15454631

RESUMO

OBJECTIVE: In contrast to the anti-proliferative properties of high-dose methotrexate (MTX) its anti-inflammatory mechanism of action in rheumatic diseases has been attributed to increased adenosine accumulation, most likely caused by long-lived intracellular MTX polyglutamates. The aim of this study was to assess adenosine concentrations in MTX-treated and untreated children and to relate it to MTX polyglutamate concentration measured in erythrocytes and to the therapeutic efficacy. METHODS: Adenosine and MTX-polyglutamate concentrations in erythrocytes (EMTX) were assessed in venous blood samples taken before the next MTX dose in 30 patients treated long-term for juvenile idiopathic arthritis (JIA) and in 16 untreated matched controls. The blood concentration of adenosine was measured by the liquid chromatography/tandem mass spectrometry (LC-MS/MS) method and EMTX by an enzymatic assay. Therapeutic efficacy was assessed using the preliminary definition of improvement in JIA patients. RESULTS: Mean blood adenosine concentration in MTX-treated patients was 48.05 nmol/l (s.d. 10.1) vs 49.6 nmol/l (s.d. 12.5) in untreated controls (P=0.55). Mean EMTX was 215.56 nmol/l (s.d. 212.9). No significant correlation was found between adenosine concentrations and MTX dose or EMTX (P=0.8 and 0.6, respectively). Adenosine concentration did not differ in clinical responders when compared with non-responders (P=0.9). CONCLUSIONS: We have shown that there is no impact of effective MTX dose represented by EMTX on blood adenosine concentration in JIA patients. If MTX anti-inflammatory action is mediated by adenosine it is likely that local release of adenosine at inflamed tissues is responsible for its action which may not be reflected by sustained increase of its blood concentration.


Assuntos
Adenosina/sangue , Artrite Juvenil/sangue , Artrite Juvenil/tratamento farmacológico , Metotrexato/análogos & derivados , Metotrexato/sangue , Ácido Poliglutâmico/análogos & derivados , Ácido Poliglutâmico/sangue , Adolescente , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Criança , Estudos Transversais , Relação Dose-Resposta a Droga , Eritrócitos/metabolismo , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Resultado do Tratamento
8.
Cas Lek Cesk ; 142(10): 615-9, 2003.
Artigo em Tcheco | MEDLINE | ID: mdl-14635427

RESUMO

BACKGROUND: Endothelial activation is an important etiopathogenetic factor in a group of disorders characterised by primary or secondary vasculitis. The aim of our study was to determine blood concentrations of von Willebrand factor (vWF), vypusteno soluble intercellular adhesion molecule-1 (ICAM-1) and E-selectin (E-sel) in children with various rheumatic diseases and in paediatric controls and to correlate them with clinical and laboratory variables. METHODS AND RESULTS: Total of 28 healthy children (ZD) and 48 patients were evaluated: 6 with systemic lupus erythematosus (SLE), 7 with other diffuse connective tissue diseases (SSD), 11 with Henoch-Schönlein purpura (HSP), 14 with oligoarticular juvenile idiopathic arthritis (JIA) and 10 febrile controls (FC). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and full blood count were recorded. ICAM-1, E-sel and vWF concentrations were measured by sandwich ELISA kits. In SLE patients' concentrations of vWF and ICAM-1 were significantly higher than in healthy (p < 0.05), but not febrile controls. ICAM-1 was significantly increased also in SSD group when compared to healthy children (p < 0.01). Differences in other groups did not reach statistical significance. Significant negative correlation with age was observed for the group as a whole, E-sel correlated with leukocyte and thrombocyte counts (p < 0.01), both molecules with CRP (p < 0.05) and with each other (p < 0.01). CONCLUSIONS: Combined measurement of vWF, ICAM-1 and E-sel as possible markers of endothelial activation in such vypusteno wide spectrum of paediatric patients and controls is unique vypusteno. Our finding of increased concentrations of vWF and/or ICAM-1 in children with systemic autoimmune diseases underlines the importance of endothelial involvement in these disorders, but their predictive value in the disease monitoring needs to be further studied.


Assuntos
Endotélio Vascular/fisiopatologia , Doenças Reumáticas/fisiopatologia , Vasculite/fisiopatologia , Adolescente , Artrite Juvenil/sangue , Artrite Juvenil/complicações , Artrite Juvenil/fisiopatologia , Biomarcadores/sangue , Criança , Pré-Escolar , Selectina E/sangue , Feminino , Humanos , Vasculite por IgA/sangue , Vasculite por IgA/fisiopatologia , Molécula 1 de Adesão Intercelular/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Doenças Reumáticas/sangue , Doenças Reumáticas/complicações , Vasculite/sangue , Vasculite/complicações , Fator de von Willebrand/análise
9.
Ann Rheum Dis ; 62(5): 444-9, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12695158

RESUMO

OBJECTIVES: To develop an objective method of nailfold capillaroscopy (NFC), applicable to a wide age range of paediatric patients. To compare the morphological characteristics of the nailfold capillaries in different rheumatology patient groups and controls. METHODS: A colour digital video camera attached to a stereomicroscope was used to capture nailfold capillary images. Computerised image processing was used to analyse and store data. Subsequent quantitative and qualitative morphological analysis was performed in the following paediatric patient and control groups: 18 children with connective tissue diseases (CTD: juvenile dermatomyositis, systemic sclerosis, and undifferentiated connective tissue disease), eight with systemic lupus erythematosus, nine with primary Raynaud's disease, three with primary vasculitis, 15 with juvenile idiopathic arthritis, 17 healthy children and 20 healthy adults. Images were analysed by a single assessor who was unaware of the patient details. RESULTS: The NFC technique was simple to perform and gave reproducible results, although some intra- and intersubject variation was noted. Capillary density and width was age related, with younger children having fewer and wider capillaries than older children and adults. Linear capillary density was significantly higher in healthy adults (mean (SD) 8.6 (1.6) capillaries/mm) compared with healthy children (HC 6.9 (0.9) capillaries/mm). The group with CTD had the most abnormal findings, with lower linear density (4.9 (1.7) capillaries/mm) and increased capillary loop width (10.7 (7.3) mm) compared with HC (3.5 (1.7) mm). In addition, 11/18 (61%) patients in the CTD group had more than two definitely abnormal capillaries in at least two nailfolds, an abnormality not seen in other subjects. Two qualitative measures, the degree of avascularity and general disarrangement of capillary pattern, were more commonly observed in the CTD group than in HC. The proportion of tortuous capillaries did not differ significantly between study groups. CONCLUSIONS: This study is unique in measuring objective quantitative and qualitative parameters of the nailfold vasculature across a wide spectrum of age and disease. Differences in capillary morphology and frequency in children with CTD compared with other paediatric diseases and healthy controls were demonstrated. In the clinical situation, an assessment of the general degree of disarrangement may offer a fast tool for assessment of the nailfold vasculature which correlates well with NFC data.


Assuntos
Doenças do Tecido Conjuntivo/patologia , Angioscopia Microscópica/métodos , Unhas/irrigação sanguínea , Doenças Vasculares/patologia , Adolescente , Capilares/patologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Prospectivos , Doença de Raynaud/patologia , Reprodutibilidade dos Testes , Doenças Reumáticas/patologia , Método Simples-Cego
10.
Clin Exp Rheumatol ; 20(2): 249-54, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12051408

RESUMO

OBJECTIVE: To determine serum and synovial fluid (SF) concentrations of soluble intercellular adhesion molecule-1 (ICAM-1) and E-selectin (E-sel) in patients with active juvenile idiopathic arthritis (JIA) and in paediatric controls and correlate them with clinical and laboratory variables. METHODS: Total of'30 JIA patients were evaluated: 15 with polyarticular disease course (JIA-poly) and 15 with oligoarthritis (JIA-oligo). Paediatric age-matched control groups consisted of 11 Henoch-Schönlein purpura (HSP) and 10 febrile patients (FC) and 28 healthy children (HC). Current medication, the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and full blood count (FBC) were recorded. Soluble ICAM-1 and E-sel in serum and SF were measured by a sandwich ELISA kit. RESULTS: In the JIA-poly group the concentration of ICAM-1 was significantly higher than in healthy (p < 0.01), but notfebrile controls. Both ICAM-1 and E-selectin correlated with the active joint count (p < 0.01). In 13 JIA patients no correlanon was found between SF ICAM-1 and E-sel levels and the SF leucocyte counts. No significant differences were seen in the disease control and JIA-oligo groups compared to HC. A significant negative correlation with age was observed for the group as a whole (ICAM-1: p < 0.05, E-sel: p < 0.01); E-sel correlated with the leucocyte and thrombocyte counts (p < 0.01), and both molecules with CRP (p < 0.05) and with each other (p < 0.01). CONCLUSION: A high concentration of soluble ICAM-1 in JIA patients with polyarthritis is reported here for the first time. None of the patients showed signs of injection or vasculitis, where generalised endothelial activation could be its main source. Our finding of correlations between both ICAM-1 and E-sel levels and joint counts supports the hypothesis of their synovial origin. ICAM- I and E-sel could serve as a marker of aggressive disease, but their predictive value needs to be further studied.


Assuntos
Artrite Juvenil/sangue , Selectina E/sangue , Molécula 1 de Adesão Intercelular/sangue , Líquido Sinovial/imunologia , Adolescente , Fatores Etários , Artrite Juvenil/imunologia , Biomarcadores/sangue , Criança , Pré-Escolar , Humanos , Lactente , Valores de Referência
11.
Clin Exp Rheumatol ; 19(4 Suppl 23): S45-9, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11510330

RESUMO

We report herein the results of the cross-cultural adaptation and validation into the Czech language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Czech CHAQ-CHQ were fully validated with 3 forward and 3 backward translations. A total of 150 subjects were enrolled: 81 patients with JIA (14% systemic onset, 44% polyarticular onset, 10% extended oligoarticular subtype, and 32% persistent oligoarticular subtype) and 69 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Czech version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.


Assuntos
Artrite Juvenil/diagnóstico , Comparação Transcultural , Nível de Saúde , Inquéritos e Questionários , Adolescente , Criança , Características Culturais , Tchecoslováquia , Avaliação da Deficiência , Feminino , Humanos , Idioma , Masculino , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes
13.
Cas Lek Cesk ; 128(12): 375-7, 1989 Mar 17.
Artigo em Tcheco | MEDLINE | ID: mdl-2731207

RESUMO

Transient hyperphosphatasaemia of child age is a condition characterized by temporary and isolated increase of alkaline phosphatase levels, in particular its bone isoenzyme.


Assuntos
Fosfatase Alcalina/sangue , Feminino , Humanos , Lactente , Isoenzimas/sangue , Masculino , Síndrome
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