Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 11 de 11
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Ann Rheum Dis ; 77(1): 128-132, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29061853

RESUMO

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc). In this longitudinal study, we aimed to identify factors associated with an unfavourable outcome in patients with SSc with early PAH (SSc-PAH) from the DETECT cohort. METHODS: Patients with SSc-PAH enrolled in DETECT were observed for up to 3 years. Associations between cross-sectional variables and disease progression (defined as the occurrence of any of the following events: WHO Functional Class worsening, combination therapy for PAH, hospitalisation or death) were analysed by univariable logistic regression. RESULTS: Of 57 patients with PAH (median observation time 12.6 months), 25 (43.9%) had disease progression. The following factors (OR (95% CI)) were associated with disease progression: male gender (4.1 (1.2 to 14.1)), high forced vital capacity % predicted/carbon monoxide lung diffusion capacity (DLCO)% predicted ratio (3.6 (1.2 to 10.7)), high Borg Dyspnoea Index (1.7 (1.1 to 2.6)) and low DLCO% predicted (non-linear relationship). CONCLUSION: More than 40% of early-diagnosed patients with SSc-PAH had disease progression during a short follow-up time, with male gender, functional capacity and pulmonary function tests at PAH diagnosis being associated with progression. This suggests that even mild PAH should be considered a high-risk complication of SSc.


Assuntos
Progressão da Doença , Hipertensão Pulmonar/fisiopatologia , Escleroderma Sistêmico/complicações , Índice de Gravidade de Doença , Adulto , Estudos Transversais , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Modelos Logísticos , Estudos Longitudinais , Pulmão/fisiopatologia , Masculino , Fatores de Risco , Escleroderma Sistêmico/fisiopatologia , Fatores Sexuais , Capacidade Pulmonar Total
2.
Arthritis Rheumatol ; 68(10): 2527-39, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27111549

RESUMO

OBJECTIVE: To identify nailfold videocapillaroscopic features and other clinical risk factors for new digital ulcers (DUs) during a 6-month period in patients with systemic sclerosis (SSc). METHODS: In this multicenter, prospective, observational cohort study, the videoCAPillaroscopy (CAP) study, we evaluated 623 patients with SSc from 59 centers (14 countries). Patients were stratified into 2 groups: a DU history group and a no DU history group. At enrollment, patients underwent detailed nailfold videocapillaroscopic evaluation and assessment of demographic characteristics, DU status, and clinical and SSc characteristics. Risk factors for developing new DUs were assessed using univariable and multivariable logistic regression (MLR) analyses. RESULTS: Of the 468 patients in the DU history group (mean ± SD age 54.0 ± 13.7 years), 79.5% were female, 59.8% had limited cutaneous SSc, and 22% developed a new DU during follow-up. The strongest risk factors for new DUs identified by MLR in the DU history group included the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs (categorized as 0, 1, 2, or ≥3), and the presence of critical digital ischemia. The receiver operating characteristic (ROC) of the area under the curve (AUC) of the final MLR model was 0.738 (95% confidence interval [95% CI] 0.681-0.795). Internal validation through bootstrap generated a ROC AUC of 0.633 (95% CI 0.510-0.756). CONCLUSION: This international prospective study, which included detailed nailfold videocapillaroscopic evaluation and extensive clinical characterization of patients with SSc, identified the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs at enrollment, and the presence of critical digital ischemia at enrollment as risk factors for the development of new DUs.


Assuntos
Dedos , Angioscopia Microscópica , Doenças Vasculares Periféricas/epidemiologia , Escleroderma Sistêmico/diagnóstico por imagem , Úlcera Cutânea/epidemiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/diagnóstico por imagem , Doenças Vasculares Periféricas/etiologia , Doenças Vasculares Periféricas/fisiopatologia , Estudos Prospectivos , Curva ROC , Fatores de Risco , Esclerodermia Limitada/complicações , Esclerodermia Limitada/diagnóstico por imagem , Escleroderma Sistêmico/complicações , Úlcera Cutânea/diagnóstico por imagem , Úlcera Cutânea/etiologia , Úlcera Cutânea/fisiopatologia
3.
Orphanet J Rare Dis ; 10: 81, 2015 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-26084276

RESUMO

BACKGROUND: Gastrointestinal (GI) disturbances such as diarrhea and flatulence are the most frequent adverse effects associated with miglustat therapy in type 1 Gaucher disease (GD1) and Niemann-Pick disease type C (NP-C), and the most common recorded reason for stopping treatment during clinical trials and in clinical practice settings. Miglustat-related GI disturbances are thought to arise from the inhibition of intestinal disaccharidases, mainly sucrase isomaltase. We report the effects of a co-administered dietary probiotic, S. boulardii, on the GI tolerability of miglustat in healthy adult subjects. METHODS: In a double-blind, placebo-controlled, two-period, two-treatment cross-over trial, healthy adult male and female subjects were randomly allocated to treatment sequences, A-B and B-A (treatment A - miglustat 100 mg t.i.d. + placebo; treatment B - miglustat 100 mg t.i.d. + S. boulardii [500 mg, b.i.d.]). GI tolerability data were collected in patient diaries. The primary endpoint was the total number of 'diarrhea days' (≥3 loose stools within a 24-h period meeting Bristol Stool Scores [BSS] 6-7) based on WHO criteria. Secondary endpoints comprised numerous other diarrhea and GI tolerability indices. RESULTS: Twenty-one subjects received randomized therapy in each treatment sequence (total N = 42), and overall, 37 (88 %) subjects completed the study. The total number of diarrhea days was <1.5 for both treatment sequences, and approximately 60 % of subjects did not experience diarrhea during either treatment period. The mean (SD) number of diarrhea days was lower with miglustat + S. boulardii (0.8 [2.4] days) than with miglustat + placebo (1.3 [2.4] days), but the paired treatment difference was not statistically significant (-0.5 [2.4] days; p = 0.159). However, a significant treatment difference (-0.7 [1.9]; p < 0.05) was identified after post hoc exclusion of a clear outlier who had a very high number of diarrhea days (n = 13) and inconsistent GI tolerability reporting. The incidence of the GI AEs was higher with miglustat + placebo (82 %) than with miglustat + S. boulardii (73 %). There were no between-treatment differences in miglustat pharmacokinetics. CONCLUSIONS: Although the primary endpoint was not met, the results of the post-hoc analysis suggest that co-administration of miglustat with S. boulardii might improve GI tolerability.


Assuntos
1-Desoxinojirimicina/análogos & derivados , Trato Gastrointestinal/efeitos dos fármacos , Saccharomyces , 1-Desoxinojirimicina/efeitos adversos , 1-Desoxinojirimicina/farmacocinética , 1-Desoxinojirimicina/uso terapêutico , Adulto , Estudos Cross-Over , Método Duplo-Cego , Inibidores Enzimáticos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos
4.
Arthritis Res Ther ; 16(6): 493, 2014 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-25491468

RESUMO

INTRODUCTION: Patients with mean pulmonary artery pressures (mPAP) of 21 to 24 mm Hg have a so-called borderline elevation of mPAP (BoPAP)--a condition thought to represent early-stage pulmonary arterial vasculopathy. Based on the DETECT study, this post-hoc analysis examined patient characteristics of systemic sclerosis (SSc) patients with normal mPAP, BoPAP and elevated mPAP, fulfilling pulmonary arterial hypertension (PAH) criteria. METHODS: Adult patients with a duration of SSc more than 3 years, a diffusing capacity of the lung for carbon monoxide less than 60% predicted, and no previous diagnosis of any form of pulmonary hypertension (PH) underwent screening tests followed by right heart catheterization. Subjects were divided into three groups: normal mPAP, BoPAP, and PAH. Exploratory comparative and binary logistic regression analyses were performed for the BoPAP versus normal mPAP and PAH versus BoPAP groups. RESULTS: Of 244 patients evaluated, 148 (60%) had normal mPAP, 36 (15%) had BoPAP, and 60 (25%) had definite PAH. Univariable logistic regression (ULR) showed the mean tricuspid regurgitation velocity in patients with BoPAP to be intermediate between normal mPAP and PAH. In the ULR analyses BoPAP versus normal mPAP and PAH versus BoPAP, the statistically significant predictors were, amongst others: demographic, clinical, pulmonary function, echocardiographic and hemodynamic variables. CONCLUSIONS: In this exploratory post-hoc analysis of the DETECT study population patients with BoPAP could be distinguished from patients with normal mPAP and PAH, and it appears that BoPAP may be an intermediate stage on the continuum between normal PA pressures and PAH.


Assuntos
Pressão Arterial , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/fisiopatologia , Artéria Pulmonar/fisiopatologia , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/fisiopatologia , Adulto , Idoso , Pressão Arterial/fisiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
5.
J Inherit Metab Dis ; 37(1): 93-101, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23793527

RESUMO

OBJECTIVE: The Suspicion Index (SI) screening tool was developed to identify patients suspected of having Niemann-Pick disease type C (NP-C). The SI provides a risk prediction score (RPS) based on NP-C manifestations within and across domains (visceral, neurological, and psychiatric). The aim of these subanalyses was to further examine the discriminatory power of the SI by age and manifestation-associations by NP-C suspicion-level and leading manifestations. METHODS: The original retrospectively collected data were split into three patient age groups, where NP-C-positive cases were >16 years (n = 30), 4-16 years (n = 18), and <4 years (n = 23), and patients' RPS were analyzed by logistic regression. Co-occurrence of manifestations within groups of suspicion level (low, medium, high) and leading manifestations (presence/absence of ataxia, cognitive decline, psychosis, and splenomegaly) were analyzed descriptively. RESULTS: NP-C-positive cases versus controls showed strong discriminatory power of RPS. Area under the receiver operating characteristic curve was 0.964 (>16 years) and 0.981 (4-16 years) but weaker 0.562 for infants (<4 years). Patients with RPS <70 were characterized by a lack of psychiatric manifestations and low levels of neurological involvement, suggestive of a preneurological phase of the disease. In patients >4 years, prominent leading manifestation-associations were ataxia with dystonia, dysarthria/dysphagia, and cognitive decline. Psychosis was associated with dysarthria/dysphagia but also with cognitive decline and treatment-resistant psychiatric symptoms. CONCLUSIONS: The SI tool maintains strong discriminatory power in patients >4 years but is not as useful for infants <4 years. The SI is also informative regarding the association and co-occurrence of manifestations in patients with NP-C.


Assuntos
Doença de Niemann-Pick Tipo C/diagnóstico , Adolescente , Fatores Etários , Ataxia/complicações , Criança , Pré-Escolar , Transtornos Cognitivos/complicações , Coleta de Dados , Técnicas de Apoio para a Decisão , Feminino , Humanos , Lactente , Modelos Logísticos , Masculino , Programas de Rastreamento/métodos , Fenótipo , Transtornos Psicóticos/complicações , Curva ROC , Estudos Retrospectivos , Risco , Esplenomegalia/complicações
6.
Ann Rheum Dis ; 73(7): 1340-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23687283

RESUMO

OBJECTIVE: Earlier detection of pulmonary arterial hypertension (PAH), a leading cause of death in systemic sclerosis (SSc), facilitates earlier treatment. The objective of this study was to develop the first evidence-based detection algorithm for PAH in SSc. METHODS: In this cross-sectional, international study conducted in 62 experienced centres from North America, Europe and Asia, adults with SSc at increased risk of PAH (SSc for >3 years and predicted pulmonary diffusing capacity for carbon monoxide <60%) underwent a broad panel of non-invasive assessments followed by diagnostic right heart catheterisation (RHC). Univariable and multivariable analyses selected the best discriminatory variables for identifying PAH. After assessment for clinical plausibility and feasibility, these were incorporated into a two-step, internally validated detection algorithm. Nomograms for clinical practice use were developed. RESULTS: Of 466 SSc patients at increased risk of PAH, 87 (19%) had RHC-confirmed PAH. PAH was mild (64% in WHO functional class I/II). Six simple assessments in Step 1 of the algorithm determined referral to echocardiography. In Step 2, the Step 1 prediction score and two echocardiographic variables determined referral to RHC. The DETECT algorithm recommended RHC in 62% of patients (referral rate) and missed 4% of PAH patients (false negatives). By comparison, applying European Society of Cardiology/European Respiratory Society guidelines to these patients, 29% of diagnoses were missed while requiring an RHC referral rate of 40%. CONCLUSIONS: The novel, evidence-based DETECT algorithm for PAH detection in SSc is a sensitive, non-invasive tool which minimises missed diagnoses, identifies milder disease and addresses resource usage.


Assuntos
Algoritmos , Cateterismo Cardíaco/métodos , Ecocardiografia/métodos , Hipertensão Pulmonar/diagnóstico , Escleroderma Sistêmico/complicações , Adulto , Idoso , Testes Respiratórios , Estudos Transversais , Diagnóstico Precoce , Medicina Baseada em Evidências , Hipertensão Pulmonar Primária Familiar , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nomogramas , Capacidade de Difusão Pulmonar , Pressão Propulsora Pulmonar , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença
7.
Hum Mol Genet ; 22(21): 4349-56, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23773996

RESUMO

Niemann-Pick disease type C (NP-C) is a rare, autosomal-recessive, progressive neurological disease caused by mutations in either the NPC1 gene (in 95% of cases) or the NPC2 gene. This observational, multicentre genetic screening study evaluated the frequency and phenotypes of NP-C in consecutive adult patients with neurological and psychiatric symptoms. Diagnostic testing for NP-C involved NPC1 and NPC2 exonic gene sequencing and gene dosage analysis. When available, results of filipin staining, plasma cholestane-3ß,5α,6ß-triol assays and measurements of relevant sphingolipids were also collected. NPC1 and NPC2 gene sequencing was completed in 250/256 patients from 30 psychiatric and neurological reference centres across the EU and USA [median (range) age 38 (18-90) years]. Three patients had a confirmed diagnosis of NP-C; two based on gene sequencing alone (two known causal disease alleles) and one based on gene sequencing and positive filipin staining. A further 12 patients displayed either single mutant NP-C alleles (8 with NPC1 mutations and 3 with NPC2 mutations) or a known causal disease mutation and an unclassified NPC1 allele variant (1 patient). Notably, high plasma cholestane-3ß,5α,6ß-triol levels were observed for all NP-C cases (n = 3). Overall, the frequency of NP-C patients in this study [1.2% (95% CI; 0.3%, 3.5%)] suggests that there may be an underdiagnosed pool of NP-C patients among adults who share common neurological and psychiatric symptoms.


Assuntos
Proteínas de Transporte/genética , Testes Genéticos , Glicoproteínas/genética , Glicoproteínas de Membrana/genética , Doença de Niemann-Pick Tipo C/diagnóstico , Doença de Niemann-Pick Tipo C/genética , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Alelos , Feminino , Variação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Doença de Niemann-Pick Tipo C/fisiopatologia , Doença de Niemann-Pick Tipo C/psicologia , Fenótipo , Análise de Sequência de DNA , Adulto Jovem
8.
Hypertension ; 55(5): 1206-9, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20231521

RESUMO

The urotensin system has been hypothesized to play an important role in the pathophysiology of diabetic nephropathy. In this multicenter, randomized, double-blind, placebo-controlled, 2-period crossover study, the effects of the urotensin receptor antagonist palosuran on urinary albumin excretion and blood pressure in hypertensive patients with type 2 diabetic nephropathy treated with a single blocker of the renin-angiotensin-aldosterone system were assessed. Patients with 24-hour albuminuria >0.5 and <3.0 g, systolic blood pressure >135 and <170 mm Hg, and/or diastolic blood pressure >85 and <110 mm Hg received both palosuran 125 mg BID and placebo for 4 weeks each. Fifty-four patients (20% women; mean age: 61.6 years, blood pressure: 155/84 mm Hg, and albuminuria: 1016 mg per 24 hours) were included in the per-protocol analysis. Palosuran did not affect albuminuria, blood pressure, glomerular filtration rate, or renal plasma flow significantly. These results question whether urotensin receptor antagonism represents a new treatment strategy in this high-risk patient population.


Assuntos
Anti-Hipertensivos/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/complicações , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Quinolinas/uso terapêutico , Ureia/análogos & derivados , Adulto , Idoso , Albuminúria/prevenção & controle , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Creatinina/urina , Estudos Cross-Over , Feminino , Humanos , Hipertensão/urina , Masculino , Pessoa de Meia-Idade , Placebos , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Sistema Renina-Angiotensina/efeitos dos fármacos , Ureia/uso terapêutico , Urotensinas/efeitos dos fármacos , Urotensinas/metabolismo
9.
Mol Genet Metab ; 99(4): 351-7, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20045366

RESUMO

A randomized, controlled trial of miglustat indicated that miglustat (Zavesca) stabilized neurological disease over 12 months in adult and juvenile patients with Niemann-Pick disease type C (NP-C). We report data from a non-controlled, open-label extension to this initial randomized trial. All patients completing the randomized trial were allowed to continue treatment in a 12-month, non-controlled open-label extension. Those completing 12 months of extension therapy could continue further on miglustat in a 'continued extension' phase. From a total of 29 patients in the randomized phase (mean [+/-SD] age 24.6+/-9.1 ears; 52% female), 21 completed 12 months of therapy with miglustat (17 of whom received miglustat in the initial randomized phase, and four in the extension phase), and 15 patients (all from the miglustat-randomized group) completed 24 months on miglustat. Mean horizontal saccadic eye movement velocity (HSEM-alpha) indicated improvement in the 12-month miglustat group, and stabilization in the 24-month group; swallowing was improved or stable in 86% and in up to 93%, respectively. Ambulation was stabilized in both the 12- and 24-month groups. In an exploratory disease stability analysis of prospective data on key parameters of disease progression (HSEM-alpha, swallowing, ambulation and cognition), 13/19 (68%) patients receiving >or= 12 months' miglustat therapy had stable disease. Among all patients receiving >or= 1 dose of miglustat (n=28), the most frequent adverse events were diarrhoea, weight decrease, flatulence and tremor. Overall, these data suggest that long-term miglustat therapy stabilizes neurological disease and is well tolerated in adult and juvenile patients with NP-C.


Assuntos
1-Desoxinojirimicina/análogos & derivados , Doença de Niemann-Pick Tipo C/tratamento farmacológico , 1-Desoxinojirimicina/efeitos adversos , 1-Desoxinojirimicina/uso terapêutico , Adolescente , Adulto , Criança , Deglutição/efeitos dos fármacos , Diarreia/induzido quimicamente , Feminino , Humanos , Caminhada , Perda de Peso
10.
J Child Neurol ; 25(3): 300-5, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19822772

RESUMO

Niemann-Pick disease type C is a rare, genetic disease associated with impaired intracellular lipid trafficking and progressive neurological symptoms. Miglustat slowed disease progression in a 12-month randomized trial in juveniles and adults with Niemann-Pick disease type C, and in a parallel, noncontrolled study in affected children. Here, the authors report the open-label extension to the pediatric study. Patients aged 4 to 12 years received open-label miglustat (dose adjusted for body surface area) for an initial 12 months, during a further 12-month extension, and a long-term, continued extension phase. Efficacy assessments included horizontal saccadic eye movement, swallowing, and ambulation. Ten children completed 24 months' treatment. Horizontal saccadic eye movement, ambulation, and swallowing were stabilized at 24 months. Analysis of key parameters of disease progression showed disease stability in 8 of 10 patients (80%). Miglustat stabilized neurological disease progression in pediatric patients with Niemann-Pick disease type C, with comparable safety and tolerability to that observed in adults and juveniles.


Assuntos
1-Desoxinojirimicina/análogos & derivados , Inibidores Enzimáticos/uso terapêutico , Doença de Niemann-Pick Tipo C/tratamento farmacológico , 1-Desoxinojirimicina/administração & dosagem , 1-Desoxinojirimicina/efeitos adversos , 1-Desoxinojirimicina/uso terapêutico , Criança , Pré-Escolar , Deglutição/efeitos dos fármacos , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Masculino , Atividade Motora/efeitos dos fármacos , Estudos Prospectivos , Movimentos Sacádicos/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento
11.
Clin Pharmacol Ther ; 80(3): 246-56, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16952491

RESUMO

OBJECTIVE: In patients with renal disease increased urotensin II plasma levels have been observed. We have investigated whether palosuran, a potent, selective, and competitive antagonist of the urotensin II receptor, has effects in patients who are prone to the development of renal disease. METHODS: Macroalbuminuric, diabetic patients, categorized by renal function, were treated with oral doses of 125 mg palosuran twice daily for 13.5 days in addition to treatment with either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. The 24-hour urinary albumin excretion rate was determined twice at baseline and after 13.5 days of treatment. Plasma concentrations of palosuran were determined for 12 hours after the first and last drug intake. Renal hemodynamics was measured before and after 12.5 days of treatment. Tolerability and safety parameters were monitored. RESULTS: An overall clinically significant reduction of 24.3% (geometric mean) (95% confidence interval, 4.1 to 45.0) in the 24-hour urinary albumin excretion rate was observed (P = .014). No effect was observed on renal hemodynamic parameters. Palosuran was rapidly absorbed with maximum plasma concentrations at 1 hour after drug administration. The accumulation factor was 1.7 (geometric mean) (95% confidence interval, 1.3 to 2.1). Palosuran was well tolerated. CONCLUSIONS: The good tolerability profile and the decrease in the 24-hour urinary albumin excretion rate may benefit diabetic patients with renal failure with regard to their disease progression. Larger placebo-controlled trials in this patient population are needed to investigate whether urotensin II receptor antagonists, given as monotherapy or combination therapy, may improve the current treatment of diabetic nephropathy.


Assuntos
Albuminúria/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Quinolinas/farmacocinética , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Ureia/análogos & derivados , Idoso , Albuminúria/tratamento farmacológico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Área Sob a Curva , Creatinina/sangue , Creatinina/urina , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/tratamento farmacológico , Fadiga/induzido quimicamente , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Cefaleia/induzido quimicamente , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Nasofaringite/induzido quimicamente , Quinolinas/efeitos adversos , Quinolinas/uso terapêutico , Circulação Renal/efeitos dos fármacos , Resultado do Tratamento , Ureia/efeitos adversos , Ureia/farmacocinética , Ureia/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA