RESUMEN

Renal involvement is one of the main complications of systemic lupus erythematosus, causing a significant impact on patients' morbidity and mortality. Renal biopsy is still the gold standard of diagnosis, but it has many limitations. In this sense, several recent studies aim to identify biomarkers that not only predict disease activity and renal histology, but also lead to earlier treatment. In previous studies, the soluble vascular cell adhesion molecule-1 measured in urine showed a strong association with the presence of lupus nephritis, with clinical and histological activity indexes of the disease and with more severe renal lesions. This paper reviews the main urinary biomarkers of lupus nephritis that have been studied, with special emphasis on vascular cell adhesion molecule-1 results.

Asunto(s)

Nefritis Lúpica/orina , Molécula 1 de Adhesión Celular Vascular/orina , Biomarcadores/orina , Estudios de Casos y Controles , Humanos , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/fisiopatología

RESUMEN

Urinary biomarkers can predict the progression of chronic kidney disease (CKD). In this study, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and N-acetyl-ß-D-glucosaminidase (NAG) were correlated with the stages of CKD, and the association of these biomarkers with CKD progression and adverse outcomes was determined. A total of 250 patients, including 111 on hemodialysis, were studied. Urinary KIM-1, NGAL, and NAG were measured at baseline. Patients not on dialysis at baseline who progressed to a worse CKD stage were compared with those who did not progress. The association of each biomarker and selected covariates with progression to more advanced stages of CKD, end-stage kidney disease, or death was evaluated by Poisson regression. NGAL was moderately correlated (rs=0.467, P<0.001) with the five stages of CKD; KIM-1 and NAG were also correlated, but weakly. Sixty-four patients (46%) progressed to a more advanced stage of CKD. Compared to non-progressors, those patients exhibited a trend to higher levels of KIM-1 (P=0.064) and NGAL (P=0.065). In patients not on dialysis at baseline, NGAL was independently associated with progression of CKD, ESKD, or death (RR=1.022 for 300 ng/mL intervals; CI=1.007-1.037, P=0.004). In patients on dialysis, for each 300-ng/mL increase in urinary NGAL, there was a 1.3% increase in the risk of death (P=0.039). In conclusion, urinary NGAL was associated with adverse renal outcomes and increased risk of death in this cohort. If baseline urinary KIM-1 and NGAL predict progression to worse stages of CKD is something yet to be explored.

Asunto(s)

Acetilglucosaminidasa/orina , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Lipocalina 2/orina , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/orina , Adulto , Factores de Edad , Anciano , Análisis de Varianza , Biomarcadores/orina , Creatinina/sangre , Creatinina/orina , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estándares de Referencia , Valores de Referencia , Diálisis Renal , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/fisiopatología , Reproducibilidad de los Resultados , Factores de Riesgo , Factores Sexuales , Estadísticas no Paramétricas

RESUMEN

Levamisole has been increasingly used as an adulterant of cocaine in recent years, emerging as a public health challenge worldwide. Levamisole-associated toxicity manifests clinically as a systemic vasculitis, consisting of cutaneous, hematological, and renal lesions, among others. Purpura retiform, cutaneous necrosis, intravascular thrombosis, neutropenia, and less commonly crescentic nephritis have been described in association with anti-neutrophil cytoplasmic antibodies (ANCAs) and other autoantibodies. Here we report the case of a 49-year-old male who was a chronic cocaine user, and who presented spontaneous weight loss, arthralgia, and 3 weeks before admission purpuric skin lesions in the earlobes and in the anterior thighs. His laboratory tests on admission showed serum creatinine of 4.56 mg/dL, white blood count 3,800/µL, hemoglobin 7.3 g/dL, urinalysis with 51 white blood cells/µL and 960 red blood cells/µL, and urine protein-to-creatinine ratio 1.20. Serum ANCA testing was positive (>1:320), as well as serum anti-myeloperoxidase and anti-proteinase 3 antibodies. Urine toxicology screen was positive for cocaine and levamisole, with 62.8% of cocaine, 32.2% of levamisole, and 5% of an unidentified substance. Skin and renal biopsies were diagnostic for leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis, respectively. The patient showed a good clinical response to cocaine abstinence, and use of corticosteroids and intravenous cyclophosphamide. Last serum creatinine was 1.97 mg/dL, white blood cell count 7,420/µL, and hemoglobin level 10.8 g/dL. In levamisole-induced systemic vasculitis, the early institution of cocaine abstinence, concomitant with the use of immunosuppressive drugs in severe cases, may prevent permanent end organ damage and associate with better clinical outcomes.

Asunto(s)

Cocaína/efectos adversos , Glomerulonefritis/inducido químicamente , Levamisol/efectos adversos , Púrpura/inducido químicamente , Vasculitis Sistémica/inducido químicamente , Glomerulonefritis/patología , Humanos , Masculino , Persona de Mediana Edad , Púrpura/patología , Vasculitis Sistémica/patología

RESUMEN

HIV infection has a broad spectrum of renal manifestations. This study examined the clinical and histological manifestations of HIV-associated renal disease, and predictors of renal outcomes. Sixty-one (64% male, mean age 45 years) HIV patients were retrospectively evaluated. Clinical presentation and renal histopathology were assessed, as well as CD4 T-cell count and viral load. The predictive value of histological lesion, baseline CD4 cell count and viral load for end-stage renal disease (ESRD) or death were determined using the Cox regression model. The outcomes of chronic kidney disease (CKD) and ESRD or death were evaluated by baseline CD4 cell count. The percent distribution at initial clinical presentation was non-nephrotic proteinuria (54%), acute kidney injury (28%), nephrotic syndrome (23%), and chronic kidney disease (22%). Focal segmental glomerulosclerosis (28%), mainly the collapsing form (HIVAN), acute interstitial nephritis (AIN) (26%), and immune complex-mediated glomerulonephritis (ICGN) (25%) were the predominant renal histology. Baseline CD4 cell count ≥ 200 cells/mm3 was a protective factor against CKD (hazard ratio=0.997; 95%CI=0.994-0.999; P=0.012). At last follow-up, 64% of patients with baseline CD4 ≥ 200 cells/mm3 had eGFR >60 mL·min-1·(1.73 m2)-1 compared to the other 35% of patients who presented with CD4 <200 cells/mm3 (log rank=9.043, P=0.003). In conclusion, the main histological lesion of HIV-associated renal disease was HIVAN, followed by AIN and ICGN. These findings reinforce the need to biopsy HIV patients with kidney impairment and/or proteinuria. Baseline CD4 cell count ≥ 200 cells/mm3 was associated with better renal function after 2 years of follow-up.

Asunto(s)

Infecciones por VIH/complicaciones , Insuficiencia Renal Crónica/virología , Nefropatía Asociada a SIDA/patología , Biopsia , Recuento de Linfocito CD4 , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular , Glomerulonefritis/patología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Proteinuria/sangre , Insuficiencia Renal Crónica/patología , Estudios Retrospectivos , Albúmina Sérica , Estadísticas no Paramétricas , Factores de Tiempo , Carga Viral

RESUMEN

Levamisole has been increasingly used as an adulterant of cocaine in recent years, emerging as a public health challenge worldwide. Levamisole-associated toxicity manifests clinically as a systemic vasculitis, consisting of cutaneous, hematological, and renal lesions, among others. Purpura retiform, cutaneous necrosis, intravascular thrombosis, neutropenia, and less commonly crescentic nephritis have been described in association with anti-neutrophil cytoplasmic antibodies (ANCAs) and other autoantibodies. Here we report the case of a 49-year-old male who was a chronic cocaine user, and who presented spontaneous weight loss, arthralgia, and 3 weeks before admission purpuric skin lesions in the earlobes and in the anterior thighs. His laboratory tests on admission showed serum creatinine of 4.56 mg/dL, white blood count 3,800/μL, hemoglobin 7.3 g/dL, urinalysis with 51 white blood cells/μL and 960 red blood cells/μL, and urine protein-to-creatinine ratio 1.20. Serum ANCA testing was positive (>1:320), as well as serum anti-myeloperoxidase and anti-proteinase 3 antibodies. Urine toxicology screen was positive for cocaine and levamisole, with 62.8% of cocaine, 32.2% of levamisole, and 5% of an unidentified substance. Skin and renal biopsies were diagnostic for leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis, respectively. The patient showed a good clinical response to cocaine abstinence, and use of corticosteroids and intravenous cyclophosphamide. Last serum creatinine was 1.97 mg/dL, white blood cell count 7,420/μL, and hemoglobin level 10.8 g/dL. In levamisole-induced systemic vasculitis, the early institution of cocaine abstinence, concomitant with the use of immunosuppressive drugs in severe cases, may prevent permanent end organ damage and associate with better clinical outcomes.

Asunto(s)

Humanos , Masculino , Persona de Mediana Edad , Púrpura/inducido químicamente , Levamisol/efectos adversos , Cocaína/efectos adversos , Vasculitis Sistémica/inducido químicamente , Glomerulonefritis/inducido químicamente , Púrpura/patología , Vasculitis Sistémica/patología , Glomerulonefritis/patología

RESUMEN

HIV infection has a broad spectrum of renal manifestations. This study examined the clinical and histological manifestations of HIV-associated renal disease, and predictors of renal outcomes. Sixty-one (64% male, mean age 45 years) HIV patients were retrospectively evaluated. Clinical presentation and renal histopathology were assessed, as well as CD4 T-cell count and viral load. The predictive value of histological lesion, baseline CD4 cell count and viral load for end-stage renal disease (ESRD) or death were determined using the Cox regression model. The outcomes of chronic kidney disease (CKD) and ESRD or death were evaluated by baseline CD4 cell count. The percent distribution at initial clinical presentation was non-nephrotic proteinuria (54%), acute kidney injury (28%), nephrotic syndrome (23%), and chronic kidney disease (22%). Focal segmental glomerulosclerosis (28%), mainly the collapsing form (HIVAN), acute interstitial nephritis (AIN) (26%), and immune complex-mediated glomerulonephritis (ICGN) (25%) were the predominant renal histology. Baseline CD4 cell count ≥200 cells/mm3 was a protective factor against CKD (hazard ratio=0.997; 95%CI=0.994-0.999; P=0.012). At last follow-up, 64% of patients with baseline CD4 ≥200 cells/mm3 had eGFR >60 mL·min-1·(1.73 m2)-1 compared to the other 35% of patients who presented with CD4 <200 cells/mm3 (log rank=9.043, P=0.003). In conclusion, the main histological lesion of HIV-associated renal disease was HIVAN, followed by AIN and ICGN. These findings reinforce the need to biopsy HIV patients with kidney impairment and/or proteinuria. Baseline CD4 cell count ≥200 cells/mm3 was associated with better renal function after 2 years of follow-up.

Asunto(s)

Humanos , Masculino , Femenino , Persona de Mediana Edad , Infecciones por VIH/complicaciones , Insuficiencia Renal Crónica/virología , Proteinuria/sangre , Factores de Tiempo , Biopsia , Albúmina Sérica , Modelos de Riesgos Proporcionales , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Nefropatía Asociada a SIDA/patología , Estadísticas no Paramétricas , Progresión de la Enfermedad , Recuento de Linfocito CD4 , Carga Viral , Insuficiencia Renal Crónica/patología , Tasa de Filtración Glomerular , Glomerulonefritis/patología

RESUMEN

BACKGROUND: Kidney graft fibrosis is a major factor related to chronic loss of kidney function. At present, the finding of fibrosis depends on the analysis of tissue in the renal biopsy, which has important limitations. In this study, we evaluated the messenger mRNA transcription and gene expression of kidney injury molecule-1 (KIM-1) in kidney tissue and in urinary sediment cells of kidney transplant patients with graft dysfunction aiming at the development of techniques that may allow the noninvasive diagnosis of interstitral fibrosis/tubular atrophy (IF/TA). PATIENTS AND METHODS: RNA extracted from cells in tissue and urine of 77 renal transplant patients whose biopsies were classified according to the Banff scheme-2007. Four diagnostic groups were established: (1) acute tubular necrosis (n = 9); (2) acute rejection (n = 49); (3) acute calcineurin inhibitors nephrotoxicity (n = 10); and (4) interstitial fibrosis and tubular atrophy (IFTA, n = 29). Tissue and urine cell RNA was amplified and quantification were made by real-time polymerase chain reactron. Data from the quantification of gene expression are presented as median and 25th to 75th percentiles. RESULTS: Messenger RNA levels of the KIM-1 gene were higher in the biopsies (26.17; 3.38-294.53) and urinary sediment cells (0.09; 0-5.81) of the patients classified as having IF/TA as compared with all others groups. A significant correlation between gene expression in samples of urine and tissue cells was found (P < .01). CONCLUSION: These initial data suggests that KIM-1 gene mRNA quantification can be used as a noninvasive biomarker of IF/TA.

Asunto(s)

Rechazo de Injerto/genética , Enfermedades Renales/genética , Trasplante de Riñón/efectos adversos , Riñón/química , Riñón/cirugía , Glicoproteínas de Membrana/genética , ARN Mensajero/análisis , Receptores Virales/genética , Atrofia , Biopsia , Femenino , Fibrosis , Marcadores Genéticos , Rechazo de Injerto/patología , Rechazo de Injerto/orina , Receptor Celular 1 del Virus de la Hepatitis A , Humanos , Inmunosupresores/efectos adversos , Riñón/efectos de los fármacos , Riñón/patología , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Enfermedades Renales/orina , Masculino , Glicoproteínas de Membrana/orina , Necrosis , Valor Predictivo de las Pruebas , ARN Mensajero/orina , Reacción en Cadena en Tiempo Real de la Polimerasa , Resultado del Tratamiento , Urinálisis

RESUMEN

AIMS: To analyse the performances of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and of Modification of Diet in Renal Disease (MDRD) study equations to estimate glomerular filtration rate (GFR) in patients with Type 2 diabetes mellitus with GFRs >60 ml/min and in healthy volunteers. METHODS: This cross-sectional study included 111 individuals (56 patients with Type 2 diabetes and 55 healthy volunteers), aged 58 ± 9 years; 54 individuals were men (49%) and ninety-eight (88%) were white. Glomerular filtration rate was measured by the (51) Cr-EDTA single-injection method ((51) Cr-GFR) and estimated according to the standardized MDRD and CKD-EPI equations. Serum creatinine was measured by a traceable Jaffe method. Bland-Altman analysis was used to examine the agreement between measured and estimated GFR. Bias, accuracy and precision were evaluated. RESULTS: In diabetic individuals, (51) Cr-GFR was 106 ± 27 ml/min/1.73 m(2) , CKD-EPI-estimated GFR 82 ± 18 ml/min/1.73 m(2) and MDRD-estimated GFR 80 ± 21 ml/min/1.73 m(2) (P < 0.001). In healthy volunteers, the corresponding values were 98 ± 20, 89 ± 13 and 84 ± 14 ml/min/1.73 m(2) (P < 0.001). The accuracy of CKD-EPI (P30) was higher in healthy volunteers than in diabetic patients (90 vs. 66%, respectively, P < 0.001). The MDRD equation performed as poorly as the CKD-EPI equation in individuals with Type 2 diabetes. CONCLUSIONS: The CKD-EPI equation is less accurate in patients with Type 2 diabetes when compared with healthy individuals, with a 2.5-fold greater bias.

Asunto(s)

Diabetes Mellitus Tipo 2/epidemiología , Nefropatías Diabéticas/epidemiología , Enfermedades Renales/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Creatinina/sangre , Estudios Transversales , Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/fisiopatología , Femenino , Tasa de Filtración Glomerular , Humanos , Enfermedades Renales/fisiopatología , Masculino , Persona de Mediana Edad

RESUMEN

The clinical relevance of anti-HLA antibodies following kidney transplantation has been a recent focus of research. Patients who present anti-HLA antibodies in the posttransplantation period have shown higher incidences of acute rejection episodes (ARE) and chronic allograft nephropathy (CAN). The objective of this study was to evaluate the presence of anti-HLA antibodies during the first year after kidney transplantation and their association with the occurrence of ARE and CAN. Eighty-eight kidney transplant recipients were evaluated for the presence of IgG anti-HLA antibodies using an enzyme-linked immunosorbent assay (LAT-M and LAT-1240, One Lambda Inc, Calif, United States). Protocol kidney biopsies were performed in consenting patients. ARE and CAN were diagnosed by clinical, laboratory, and histopathological criteria. Anti-HLA antibodies were observed in 20 (22.7%) patients. At 1 year follow-up, 26.1% presented ARE and 51.2% developed CAN. Nine patients (45%) with antibodies developed ARE as opposed to 20.6% without antibodies and 64.7% developed CAN as opposed to 47.8% of those without antibodies. In the histological analysis, the anti-HLA antibodies were associated with Banff IIA ARE (P = .001) and Banff grade II CAN (P = .012). Routine posttransplantation search for antibodies may identify cases at higher risk for acute and chronic rejection, and perhaps help to tailor the immunosuppressive regimen.

Asunto(s)

Autoanticuerpos/sangre , Rechazo de Injerto/inmunología , Rechazo de Injerto/patología , Antígenos HLA/inmunología , Trasplante de Riñón/inmunología , Enfermedad Aguda , Estudios de Seguimiento , Rechazo de Injerto/sangre , Humanos , Complicaciones Posoperatorias/inmunología , Factores de Tiempo , Trasplante Homólogo/inmunología

RESUMEN

Delayed graft function (DGF) often occurs in kidney transplants from deceased donors. We wanted to provide studies giving more accurate non-invasive tests for acute rejection (AR). Using real-time PCR, we examined the expression of cytolytic molecules such as perforin, granzyme B, and fas-ligand along with serpin proteinase inhibitor-9. We also measured the expression of FOXP3, a characteristic gene of T-regulatory cells known to be involved in AR. These studies were conducted on peripheral blood monocytes, urinary cells, and 48 surveillance kidney biopsies taken from a total of 35 patients with DGF. Of these patients, 20 had a histopathological diagnosis of AR, whereas other 28 had characteristics of acute tubular necrosis (ATN). Expression of cytolytic and apoptotic-associated genes in the biopsy tissue, peripheral blood leukocytes, and urinary cells was significantly higher in patients with AR than that in patients with ATN. Diagnostic parameters associated with FOXP3 gene expression were most accurate in peripheral blood leukocytes and urine cells with sensitivity, specificity, positive and negative predictive values, and accuracy between 94 and 100%. Our study shows that quantification of selected genes in peripheral blood leukocytes and urinary cells from renal transplant patients with DGF may provide a useful and accurate non-invasive diagnosis of AR.

Asunto(s)

Funcionamiento Retardado del Injerto/diagnóstico , Rechazo de Injerto/diagnóstico , Trasplante de Riñón , Enfermedad Aguda , Adulto , Biopsia , Femenino , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

Renal biopsy is currently the gold standard to assess the causes of renal allograft dysfunction. In the present study, we prospectively assessed the role of the renal allograft biopsy in the diagnosis and treatment of renal allograft dysfunction. Seven hundred and fifteen biopsies were performed in 399 patients. The anatomopathological results in group 1 (delayed graft function) were: 60.4% acute tubular necrosis, 17.6% acute rejection, 4.3% calcineurin inhibitor toxicity, and 17.7% other diagnoses; in group 2 (acute graft dysfunction): 42.3% acute rejection, 22% acute tubular necrosis, 8.4% calcineurin inhibitor toxicity, and 27.3% other diagnoses. Among patients with delayed graft function, 42.2% of biopsies led to a change in the treatment. In 60.5%, the biopsy of patients with acute dysfunction led to a change in the patient management. In our series, the result of the biopsy disagreed with the clinical diagnosis in 39.6% and 57.7% of cases, respectively. These results demonstrated that renal graft biopsy remains an indispensable tool for the accurate management of kidney transplant patients.

Asunto(s)

Trasplante de Riñón/patología , Trasplante de Riñón/fisiología , Complicaciones Posoperatorias/patología , Adulto , Biopsia , Femenino , Rechazo de Injerto/epidemiología , Rechazo de Injerto/patología , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/clasificación , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Trasplante Homólogo/patología , Trasplante Homólogo/fisiología

Asunto(s)

Azatioprina/uso terapéutico , Hepatitis C/inmunología , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Pruebas de Función Hepática , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Brasil , Humanos

Asunto(s)

Biopsia/métodos , Trasplante de Riñón/patología , Estudios de Seguimiento , Rechazo de Injerto/patología , Humanos , Complicaciones Posoperatorias/patología , Factores de Tiempo

Asunto(s)

Rechazo de Injerto/tratamiento farmacológico , Supervivencia de Injerto , Inmunosupresores/uso terapéutico , Trasplante de Riñón/fisiología , Muromonab-CD3/uso terapéutico , Adulto , Resistencia a Medicamentos , Femenino , Estudios de Seguimiento , Rechazo de Injerto/inmunología , Humanos , Trasplante de Riñón/inmunología , Trasplante de Riñón/mortalidad , Masculino , Reoperación , Esteroides/uso terapéutico , Tasa de Supervivencia , Factores de Tiempo , Trasplante Homólogo

Asunto(s)

Biopsia/normas , Trasplante de Riñón/patología , Trasplante de Riñón/fisiología , Enfermedad Aguda , Adulto , Biopsia/métodos , Cadáver , Creatinina/sangre , Ciclosporina/efectos adversos , Quimioterapia Combinada , Femenino , Rechazo de Injerto/patología , Humanos , Inmunosupresores/uso terapéutico , Donadores Vivos , Masculino , Embarazo , Proteinuria , Donantes de Tejidos

Asunto(s)

Rechazo de Injerto/patología , Trasplante de Riñón/patología , Biopsia , Humanos , Trasplante de Riñón/efectos adversos

Asunto(s)

Glomeruloesclerosis Focal y Segmentaria/complicaciones , Glomeruloesclerosis Focal y Segmentaria/cirugía , Trasplante de Riñón , Sarcoidosis Pulmonar/complicaciones , Adulto , Femenino , Estudios de Seguimiento , Glomeruloesclerosis Focal y Segmentaria/patología , Humanos , Riñón/patología

RESUMEN

Nerve regeneration experiments were carried out using tubular nerve guides of poly[(ethylalanato)1.4(imidazolyl)0.6phosphazene] (PEIP). By means of in vivo tests, this polymer was found to be biodegradable and transformed into harmless products. The tubular nerve guides were prepared by deposition of the dissolved polymer on a glass capillary tube, followed by evaporation of the solvent (methylene dichloride). After transectioning, rat sciatic nerve stumps were immediately sutured into the ends of 10-mm-long polymer tubes. On removal of the prosthesis, after implantation for 45 d, a tissue cable was found bridging the nerve stumps in all cases. Histological analysis revealed that the tissue cable was essentially composed of a regenerated nerve fibre bundle. A parallel series of experiments was undertaken to compare the use of silicone tubes that are not biodegradable and are most frequently used for studies of nerve regeneration with tubulization techniques. The advantages of biodegradable PEIP tubular nerve guides used for peripheral nerve repair are discussed.

Asunto(s)

Materiales Biocompatibles , Regeneración Nerviosa , Compuestos Organofosforados , Sistema Nervioso Periférico/cirugía , Polímeros , Prótesis e Implantes , Animales , Sistema Nervioso Periférico/fisiología , Ratas , Nervio Ciático/cirugía , Siliconas

Asunto(s)

Anciano , Humanos , Femenino , Nitrofurazona , Insuficiencia Respiratoria , Mediciones del Volumen Pulmonar