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1.
Rheumatol Int ; 39(11): 1875-1882, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31522232

RESUMO

The objective of this study was to evaluate the impact of digital ulcers (DUs) in daily life of systemic sclerosis (SSc) Spanish patients. We developed a multicenter observational study to compare functional disability in SSc patients with active DUs vs. those without DUs. An additional correlation between perception of patients and physicians on disability due to DUs was performed. A total of 199 patients were enrolled, 70 (35%) with DUs. Patients with DUs were younger (48 vs. 58 years; p < 0.001) and had more frequently the diffuse subtype of SSc (45 vs. 24%; p = 0.004) than patients without DUs. Patients with DUs showed significantly higher scores in the Cochin Hand Function Scale overall (p < 0.002) and for each of its five dimensions. They also showed higher scores in the Systemic Sclerosis Health Assessment Questionnaire items related to hand function such as, dress and self-care (p < 0.013), eat (p < 0.013) and grip (p < 0.03), and higher Visual Analogic Scale scores for pain (p < 0.013), trouble related with Raynaud's Phenomenon (p < 0.001) and sense of severity (p < 0.004). Impact on daily activities was significantly higher in patients with DUs (p = 0.002), with a non-significant trend to experience higher impact on work productivity (p = 0.07). A high correlation was found between DUs patients and physicians opinion on the impact of DUs (daily life: Pearson R = 0.86; work productivity: Pearson R = 0.87). Study findings show an impaired hand function and increased disability for daily life activities and work productivity in SSc patients with DUs compared with patients without DUs in Spanish population.

3.
PLoS One ; 13(1): e0189498, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29293537

RESUMO

Gene-level analysis of ImmunoChip or genome-wide association studies (GWAS) data has not been previously reported for systemic sclerosis (SSc, scleroderma). The objective of this study was to analyze genetic susceptibility loci in SSc at the gene level and to determine if the detected associations were shared in African-American and White populations, using data from ImmunoChip and GWAS genotyping studies. The White sample included 1833 cases and 3466 controls (956 cases and 2741 controls from the US and 877 cases and 725 controls from Spain) and the African American sample, 291 cases and 260 controls. In both Whites and African Americans, we performed a gene-level analysis that integrates association statistics in a gene possibly harboring multiple SNPs with weak effect on disease risk, using Versatile Gene-based Association Study (VEGAS) software. The SNP-level analysis was performed using PLINK v.1.07. We identified 4 novel candidate genes (STAT1, FCGR2C, NIPSNAP3B, and SCT) significantly associated and 4 genes (SERBP1, PINX1, TMEM175 and EXOC2) suggestively associated with SSc in the gene level analysis in White patients. As an exploratory analysis we compared the results on Whites with those from African Americans. Of previously established susceptibility genes identified in Whites, only TNFAIP3 was significant at the nominal level (p = 6.13x10-3) in African Americans in the gene-level analysis of the ImmunoChip data. Among the top suggestive novel genes identified in Whites based on the ImmunoChip data, FCGR2C and PINX1 were only nominally significant in African Americans (p = 0.016 and p = 0.028, respectively), while among the top novel genes identified in the gene-level analysis in African Americans, UNC5C (p = 5.57x10-4) and CLEC16A (p = 0.0463) were also nominally significant in Whites. We also present the gene-level analysis of SSc clinical and autoantibody phenotypes among Whites. Our findings need to be validated by independent studies, particularly due to the limited sample size of African Americans.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Grupo com Ancestrais do Continente Europeu/genética , Estudo de Associação Genômica Ampla , Escleroderma Sistêmico/genética , Humanos , Polimorfismo de Nucleotídeo Único
4.
Ann Rheum Dis ; 75(8): 1521-6, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26338038

RESUMO

OBJECTIVES: TYK2 is a common genetic risk factor for several autoimmune diseases. This gene encodes a protein kinase involved in interleukin 12 (IL-12) pathway, which is a well-known player in the pathogenesis of systemic sclerosis (SSc). Therefore, we aimed to assess the possible role of this locus in SSc. METHODS: This study comprised a total of 7103 patients with SSc and 12 220 healthy controls of European ancestry from Spain, USA, Germany, the Netherlands, Italy and the UK. Four TYK2 single-nucleotide polymorphisms (V362F (rs2304256), P1104A (rs34536443), I684S (rs12720356) and A928V (rs35018800)) were selected for follow-up based on the results of an Immunochip screening phase of the locus. Association and dependence analyses were performed by the means of logistic regression and conditional logistic regression. Meta-analyses were performed using the inverse variance method. RESULTS: Genome-wide significance level was reached for TYK2 V362F common variant in our pooled analysis (p=3.08×10(-13), OR=0.83), while the association of P1104A, A928V and I684S rare and low-frequency missense variants remained significant with nominal signals (p=2.28×10(-3), OR=0.80; p=1.27×10(-3), OR=0.59; p=2.63×10(-5), OR=0.83, respectively). Interestingly, dependence and allelic combination analyses showed that the strong association observed for V362F with SSc, corresponded to a synthetic association dependent on the effect of the three previously mentioned TYK2 missense variants. CONCLUSIONS: We report for the first time the association of TYK2 with SSc and reinforce the relevance of the IL-12 pathway in SSc pathophysiology.


Assuntos
Interleucina-12/fisiologia , Polimorfismo de Nucleotídeo Único , Escleroderma Sistêmico/genética , TYK2 Quinase/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Mutação de Sentido Incorreto , Escleroderma Sistêmico/imunologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia
5.
Clin Exp Rheumatol ; 33(4 Suppl 91): S31-5, 2015 Jul-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26314374

RESUMO

OBJECTIVES: The current knowledge of the influence of systemic sclerosis (SSc) risk loci in the clinical sub-phenotypes is still limited. The main limitation lies in the low frequency of some sub-phenotypes which could be solved by replication studies in independent cohorts and meta-analysis between studies. In this regard, CCR6 gene variants have been recently associated with anti-topoisomerase I positive (ATA+) production in SSc patients in a candidate gene study. This gene has been proposed to have a critical role in IL-17-driven autoimmunity in human diseases. METHODS: In order to confirm the association between CCR6 and ATA+ SSc patients, we performed an independent replication study in populations of European ancestry. We studied two CCR6 genetic variants (rs968334 and rs3093024) in a total of 901 ATA+ SSc cases, 3,258 ATA- SSc cases and 7,865 healthy controls and compared allelic frequencies for those SNPs in ATA+ SSc with healthy controls and also with ATA- SSc patients. RESULTS: The comparison performed between ATA+ SSc patients and healthy controls showed significant association with SNP rs968334 (p=4.88x10(-2), OR=1.11). When we compared ATA+ SSc cases with ATA- SSc, both SNPs, rs3093024 and rs968334, showed significant associations (p=2.89x10(-2), OR=1.13; p=1.69x10(-2), OR=1.15). Finally, in order to increase even more sample size and statistical power, we meta-analysed our study with the previous reported and found a significant association between SNP rs3093024 and ATA+ SSc patients (p=1.00x10(-4), OR=1.16) comparing with healthy controls. CONCLUSIONS: Our work confirms the association of CCR6 gene and ATA+ SSc patients.


Assuntos
Autoanticorpos/sangue , DNA Topoisomerases Tipo I/imunologia , Polimorfismo de Nucleotídeo Único , Receptores CCR6/genética , Escleroderma Sistêmico/genética , Biomarcadores/sangue , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Europa (Continente) , Grupo com Ancestrais do Continente Europeu/genética , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Razão de Chances , Fenótipo , Fatores de Risco , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/etnologia , Estados Unidos/epidemiologia
7.
Semin Arthritis Rheum ; 44(2): 208-19, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24931517

RESUMO

OBJECTIVE: To determine the mortality, survival, and causes of death in patients with systemic sclerosis (SSc) through a meta-analysis of the observational studies published up to 2013. METHODS: We performed a systematic review and meta-analysis of the observational studies in patients with SSc and mortality data from entire cohorts published in MEDLINE and SCOPUS up to July 2013. RESULTS: A total of 17 studies were included in the mortality meta-analysis from 1964 to 2005 (mid-cohort years), with data from 9239 patients. The overall SMR was 2.72 (95% CI: 1.93-3.83). A total of 43 studies have been included in the survival meta-analysis, reporting data from 13,529 patients. Cumulative survival from onset (first Raynaud's symptom) has been estimated at 87.6% at 5 years and 74.2% at 10 years, from onset (non-Raynaud's first symptom) 84.1% at 5 years and 75.5% at 10 years, and from diagnosis 74.9% at 5 years and 62.5% at 10 years. Pulmonary involvement represented the main cause of death. CONCLUSIONS: SSc presents a larger mortality than general population (SMR = 2.72). Cumulative survival from diagnosis has been estimated at 74.9% at 5 years and 62.5% at 10 years. Pulmonary involvement represented the main cause of death.


Assuntos
Escleroderma Sistêmico/mortalidade , Adulto , Feminino , Humanos , Pneumopatias/etiologia , Pneumopatias/mortalidade , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/complicações , Taxa de Sobrevida , Fatores de Tempo
8.
Medicine (Baltimore) ; 93(2): 73-81, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24646463

RESUMO

Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ≤ 30 years (early onset), age between 31 and 59 years (standard onset), and age ≥ 60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients.


Assuntos
Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/fisiopatologia , Adulto , Idade de Início , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento
9.
Am J Hum Genet ; 94(1): 47-61, 2014 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-24387989

RESUMO

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.


Assuntos
Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 3/genética , Loci Gênicos , Predisposição Genética para Doença , Escleroderma Sistêmico/genética , Alelos , Proteína 5 Relacionada à Autofagia , Proteínas de Transporte/genética , Estudos de Casos e Controles , RNA Helicases DEAD-box/genética , Endodesoxirribonucleases/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Antígenos HLA/genética , Humanos , Subunidade p35 da Interleucina-12/genética , Desequilíbrio de Ligação , Modelos Logísticos , Masculino , Procedimentos Analíticos em Microchip , Proteínas Associadas aos Microtúbulos/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas/genética , Fatores de Risco
10.
Arch Bronconeumol ; 48(1): 8-13, 2012 Jan.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-22133713

RESUMO

BACKGROUND: Induced sputum is a non-invasive method for studying pulmonary inflammation. OBJECTIVES: To assess pulmonary inflammation by analysis of induced sputum specimens in patients with systemic sclerosis and lung involvement, and to determine whether there is a correlation with the pulmonary function alterations in these patients. METHODS: Twenty-five patients with systemic sclerosis were included (20 women). Patients were divided into 3 groups according to the type of lung involvement: group 1, diffuse interstitial lung disease (n=10); group 2, those with pulmonary arterial hypertension (n=7), and group 3, patients with systemic sclerosis without lung involvement (n=8). All patients underwent a complete lung function study. Induced sputum samples were obtained and differential cell count was performed by optic microscopy. RESULTS: The mean percentage of sputum neutrophils was 85%, 71%, and 75% for groups 1, 2, and 3, respectively. A significant negative correlation between sputum total cell count and DLCO was seen in group 1 and group 3 (r=-0.733, P=.016; and r=-0.893, P=.007, respectively). This negative correlation was not observed in group 2. CONCLUSIONS: Pulmonary inflammation was present in all patients with systemic sclerosis included in the study, regardless of the presence of documented signs of pulmonary involvement. This finding suggests that induced sputum could be helpful for detecting early abnormalities indicative of subclinical pulmonary involvement in patients with systemic sclerosis.


Assuntos
Hipertensão Pulmonar/etiologia , Doenças Pulmonares Intersticiais/etiologia , Fibrose Pulmonar/etiologia , Escleroderma Sistêmico/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Gasometria , Contagem de Células , Estudos Transversais , Teste de Esforço , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/patologia , Inflamação , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/patologia , Medidas de Volume Pulmonar , Masculino , Pessoa de Meia-Idade , Neutrófilos , Fibrose Pulmonar/diagnóstico , Fibrose Pulmonar/patologia , Testes de Função Respiratória , Escarro/citologia , Adulto Jovem
11.
J Rheumatol ; 38(8): 1631-5, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21632679

RESUMO

OBJECTIVE: To describe treatment outcomes and safety experience with bosentan in patients with systemic sclerosis (SSc) and digital ulcers (DU), in a clinical setting in Spain. METHODS: This was a multicenter, noninterventional retrospective cohort study. Data were collected retrospectively from patients with DU, with or without pulmonary arterial hypertension (PAH), who were initiating bosentan therapy in 2003 (n = 26) or 2004 (n = 41) and followed until May 2005. Data were obtained from centers prescribing bosentan. Relevant measures included number of DU, occurrence of new DU, overall DU clinical status (improved, stabilized, worsened), and bosentan-associated adverse events. RESULTS: Sixty-seven patients with SSc and DU or other ulcers were included. PAH was also present in 12 patients (18%). At the start of bosentan treatment, the median number of DU per patient was 3.0. The median change in number of DU was -3.6 and -5.0 at 12 and 24 months, respectively. Sixty-eight percent of the patients did not develop any new DU at 12 months. DU clinical status was reported at 12 months for 22 patients: 18 patients (81.8%) improved and 4 (18.2%) stabilized. The median treatment duration was 13.0 months. The main adverse event was increase of aminotransferase, observed in 5 patients (7%), leading to discontinuation of treatment in 3 patients (4.4%). CONCLUSION: Previously reported results of bosentan efficacy in DU management are reproducible in clinical practice. This efficacy is maintained in the longterm followup. Bosentan treatment was well tolerated and adverse events were comparable with those observed in previous reports.


Assuntos
Isquemia/patologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/etiologia , Sulfonamidas/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bosentana , Estudos de Coortes , Humanos , Hipertensão/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Escleroderma Sistêmico/patologia , Úlcera Cutânea/patologia , Espanha , Resultado do Tratamento
12.
Arch Bronconeumol ; 47(5): 239-45, 2011 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-21458128

RESUMO

BACKGROUND: Cyclophosphamide (CYC) stabilizes the parameters of lung function tests (LFT) of patients with (SSc) and interstitial lung disease (ILD) treated for 12 months. There is little information about long-term treatment (24 months). The aim of this study is to analyze the effect of intravenous CYC in LFT parameters in patients with SSc and ILD treated for 24 months. PATIENTS AND METHOD: Retrospective study of 37 patients with ILD associated with scleroderma treated with intravenous CYC for 24 months and regularly assessed by LFT (at baseline, 6, 12 and 24 months) including forced vital capacity (FVC) and transfer capacity of carbon monoxide (DL(CO)). To evaluate response to treatment the recommendations of the ATS and SEPAR were considered. RESULTS: The difference between FVC and DL(CO) values performed at baseline and those performed at 6, 12, and 24 months were less than 10%, which meant that CYC stabilized LFT. There were no differences in LFT when patients treated for 6 months were evaluated according to the type of skin involvement of the SSc (diffuse or limited) and the duration of the ILD. Although patients with severe restriction (FVC<70%) showed more improvement, it was less than 10% in all cases. CONCLUSION: In this series of patients with ILD associated with SSc intravenous CYC was effective in stabilizing LFT in long-term treatment.


Assuntos
Ciclofosfamida/uso terapêutico , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Escleroderma Sistêmico/complicações , Adulto , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Imunossupressores/administração & dosagem , Masculino , Estudos Retrospectivos
13.
BMJ Case Rep ; 20092009.
Artigo em Inglês | MEDLINE | ID: mdl-22190980

RESUMO

This case report concerns a 49-year-old woman whose physical examination was remarkable for symmetrical swollen hands, fingers and palmar fascial thickening with erythema. The fingers showed flexion contractures. Examination also revealed markedly limited bilateral shoulder and limited knee flexion.The patient's symptoms were treated with rehabilitation. The immunological laboratory investigations were normal. A technetium scan showed a slightly increased uptake in both shoulders, wrists, hips, knees and ankles. CT revealed a pelvic solid mass next to the uterus. After the patient underwent a total hysterectomy and anexectomy, the polyarthritis showed a gradual improvement but the contractures in the hands persisted.Palmar fasciitis and polyarthritis syndrome (PFPAS) is an uncommon rheumatic disorder consisting of pain, swelling, stiffness, progressive flexion contractures of both hands and thickening of palmar fascia, with erythrosis. It was first described as a paraneoplastic phenomenon with ovarian carcinoma in 1982.The characteristic hand deformities of PFPA should alert the clinician to search for an underlying malignant disease.

14.
Med Clin (Barc) ; 122(7): 253-5, 2004 Feb 28.
Artigo em Espanhol | MEDLINE | ID: mdl-15012873

RESUMO

BACKGROUND AND OBJECTIVE: We aimed to asses the efficacy of pilocarpine tablets as a symptomatic treatment for dry mouth and dry eyes in patients with primary Sjögren's syndrome (SS). PATIENTS AND METHOD: We included 40 patients with SS (38 women and 2 men), mean age 49.2 years (range, 35-68), with severe xerostomia and xerophthalmia. Objective tests (salivary scintigraphy, Schirmer's test, break-up time, Rose Bengal staining) and subjective tests (symptoms' questionnaire) were carried out before starting treatment and 6 months later to evaluate any glandular function improvement. RESULTS: All patients initially received 15 mg daily of pilocarpine. Twelve (30%) patients received 20 mg daily. Dry mouth-related symptoms improved in 57.5% of patients and dry eyes-related ones improved in 35%. Scintigraphic studies demonstrated an objective improvement of the glandular function in 35% patients. Ocular tests showed an improvement in 30% cases. CONCLUSIONS: Pilocarpine therapy is useful to improve xerostomia and xerophthalmia in SS patients with moderate and severe glandular involvement. However, we have not observed a good correlation between subjective improvement of symptoms and the objective test results.


Assuntos
Mióticos/uso terapêutico , Pilocarpina/uso terapêutico , Síndrome de Sjogren/tratamento farmacológico , Xeroftalmia/tratamento farmacológico , Administração Oral , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Sjogren/complicações , Resultado do Tratamento , Xeroftalmia/etiologia , Xerostomia/tratamento farmacológico , Xerostomia/etiologia
15.
Med. clín (Ed. impr.) ; 122(7): 253-255, mar. 2004.
Artigo em Espanhol | IBECS | ID: ibc-30387

RESUMO

FUNDAMENTO Y OBJETIVO: Evaluar la eficacia de la pilocarpina en el tratamiento de la xerostomía y xeroftalmía en pacientes afectados de síndrome de Sjögren primario. PACIENTES Y MÉTODO: Se incluyó a 40 enfermos (38 mujeres y 2 varones), con una edad media de 49,2 años (intervalo, 35-68), con xerostomía y xeroftalmía intensas. Se practicaron pruebas objetivas (gammagrafía salival, prueba de Schirmer, tiempo de rotura lagrimal, tinción corneal con rosa de Bengala) y subjetivas (cuestionario de síntomas) para valorar la función glandular antes de inicio del tratamiento y a los 6 meses. RESULTADOS: Todos los pacientes recibieron inicialmente 15 mg/día de pilocarpina distribuidos en 3 tomas; 12 (30 por ciento) recibieron 20 mg/día. El 57,5 por ciento refirió mejoría subjetiva de la xerostomía y el 35 por ciento, de la xeroftalmía. La xerostomía mejoró objetivamente en el 35 por ciento de los pacientes y la xeroftalmía, en el 30 por ciento. CONCLUSIONES: El tratamiento con pilocarpina es beneficioso en pacientes con síndrome de Sjögren primario con moderada o escasa función glandular. No siempre existe una adecuada correlación entre la mejoría objetiva y la subjetiva (AU)


Assuntos
Pessoa de Meia-Idade , Adulto , Idoso , Masculino , Feminino , Humanos , Xeroftalmia , Xerostomia , Resultado do Tratamento , Mióticos , Pilocarpina , Administração Oral , Síndrome de Sjogren
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