RESUMEN
The high incidence of cardiovascular disease in hemodialyzed (HD) patients is well established and oxidative stress has been involved in this phenomenon. The aim of our study was to evaluate if a vitamin E-coated dialyzer could offer protection to HD patients against oxidative stress. Sixteen HD patients were successively assessed for one month (i) on a high biocompatible synthetic dialyzer (AN) and (ii) on a vitamin E-coated dialyzer (VE). Blood samples were taken before and after the dialysis session at the end of each treatment period. HD session conducted with the AN dialyzer was responsible for acute oxidative stress, significantly assessed after HD by a decreased plasma vitamin C level and an increased ascorbyl free radical (AFR)/vitamin C ratio used as an index of oxidative stress. Plasma elastase activity, reflecting neutrophil activation, was also increased; soluble P-selectin, reflecting platelet activation, did not show any variation. The use of the VE dialyzer was associated with a less extended oxidative stress compared with the AN membrane: basal vitamin C level was higher, and after the HD session AFR/vitamin C ratio and elastase activity were not significantly increased. Plasma vitamin E levels were not affected. Our study demonstrates that HD is associated with oxidative stress, which can be partially prevented by the use of a vitamin E-coated dialyzer. Our data suggest that this dialyzer may exert a site-specific scavenging effect on free radical species in synergy with a reduced activation of neutrophils.
Asunto(s)
Antioxidantes/farmacología , Riñones Artificiales , Estrés Oxidativo/efectos de los fármacos , Diálisis Renal , Vitamina E/farmacología , Anciano , Ácido Ascórbico/sangre , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/prevención & control , Estudios Cruzados , Femenino , Radicales Libres/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Elastasa Pancreática/sangre , Estudios Prospectivos , Diálisis Renal/efectos adversosRESUMEN
OBJECTIVE: The high incidence of cardiovascular diseases in chronic renal failure (CRF) and hemodialyzed (HD) patients is now well established and the involvement of oxidative stress has been hypothesized in these phenomena. The aim of our study was to evaluate the level of oxidative stress in healthy controls (CTL) compared with CRF and HD patients before (pre-HD) and after (post-HD) the dialysis session, carried out on a high biocompatible polyacrylonitrile membrane AN69. METHODS: Several indicators of the extracellular redox status were evaluated in plasma. The ascorbyl free radical (AFR) was directly measured using electron spin resonance spectroscopy (ESR) and expressed with respect to the vitamin C level to obtain a direct index of oxidative stress. Indirect plasma parameters such as vitamin E, thiol and uric acid levels were also quantified. The plasma antioxidant status (PAS) was evaluated by the allophycocyanin test. Nitric oxide (NO) stable-end metabolites: nitrites and nitrates (NO(x)), were measured in plasma. RESULTS: In CRF patients, vitamin C and thiol levels were low, and the AFR/vitamin C ratio high compared with the CTL. On the other hand, PAS and uric acid levels were shown to be higher in CRF patients. After the dialysis session, vitamin C level decreased and AFR/vitamin C ratio increased. The thiol levels were shown to be increased, in return PAS and uric acid levels were significantly lower after the dialysis session. NO(x) levels rose during CRF, but were significantly decreased after the dialysis procedure. No differences in vitamin E status were observed between CTL, CRF and HD patients. CONCLUSION: Our study demonstrates that profound disturbances in the extracellular redox system occur during the course of chronic renal failure and hemodialysis, and may provide an explanation for the cardiovascular complications in these patients.
Asunto(s)
Antioxidantes/análisis , Enfermedades Cardiovasculares/etiología , Fallo Renal Crónico/complicaciones , Anciano , Análisis de Varianza , Ácido Ascórbico/sangre , Enfermedades Cardiovasculares/sangre , Estudios de Casos y Controles , Colesterol/sangre , Espectroscopía de Resonancia por Spin del Electrón , Femenino , Radicales Libres/análisis , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Nitratos/sangre , Óxido Nítrico/sangre , Nitritos/sangre , Estrés Oxidativo , Diálisis Renal , Factores de Riesgo , Compuestos de Sulfhidrilo/análisis , Ácido Úrico/sangre , Vitamina E/sangreRESUMEN
A French family with hereditary renal amyloidosis (HRA) was studied. The disease presented in 7 of the 8 affected individuals with proteinuria or the nephrotic syndrome. The age of onset was in the fifth decade of life. There is currently no sign of extrarenal involvement in any affected individual. However, the nephropathy in this family is progressive and led to terminal renal failure in 4 patients. Immunohistochemistry studies of glomerular amyloid deposits suggested that the amyloid protein was the fibrinogen A alpha chain. Direct DNA sequencing revealed a G 4993 T transversion and subsequently Arg 554 Leu mutation in the fibrinogen A alpha chain. This is the first description of this fibrinogen A alpha chain mutation in Europe. This family is of French descent and cannot be related to the previously reported Peruvian/Mexican and African-American kindreds.
Asunto(s)
Amiloidosis/genética , Arginina/genética , Fibrinógenos Anormales/genética , Enfermedades Renales/genética , Leucina/genética , Mutación , Adulto , Anciano , Sustitución de Aminoácidos , Secuencia de Bases , ADN , Femenino , Fibrinógenos Anormales/química , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Linaje , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
In the following we describe a case of nephropathia epidemica, which exhibited, a few years after acute infection, arterial hypertension and multiple papillary necrosis. Papillary necrosis was diagnosed by i.v. pyelography and CT Scan. A complete evaluation of the patient failed to show any other etiology for medullary necrosis. If arterial hypertension has already been reported as a complication of nephropathia epidemica, papillary necrosis is exceptional, but may be explained by the severe vascular troubles engendered by Hantavirus infection in kidney medulla.
Asunto(s)
Infecciones por Hantavirus/complicaciones , Infecciones por Hantavirus/diagnóstico por imagen , Necrosis Papilar Renal/diagnóstico por imagen , Necrosis Papilar Renal/etiología , Adulto , Orthohantavirus/inmunología , Humanos , Masculino , Tomografía Computarizada por Rayos XRESUMEN
Lecithin:cholesterol acyltransferase (LCAT) is responsible for the formation of the majority of plasma cholesteryl esters. Familial LCAT deficiency is associated with corneal opacity, anemia and proteinurea and typically results in renal failure in the 4-5th decade; this syndrome is equally characterized by the quasi-absence of plasma LCAT activity with variable enzyme mass and very low levels of plasma cholesteryl esters. In this study, we report detailed analyses of plasma lipids and lipoprotein profile in two sisters (CM and ML) presenting classical homozygous LCAT-deficiency; the younger sibling (CM) had proteinurea from an early age whereas the older sister (ML) has never exhibited renal dysfunction. We investigated the molecular defect in the 45 year-old woman (proband CM) exhibiting all clinical and biochemical features of familial LCAT deficiency: a plasma cholesterol level of 105 mg/dl, of which 95% was unesterified, an HDL-cholesterol of 6.5 mg/dl and an apo A-I level of 52 mg/dl. The proband (CM) displayed a plasma cholesterol esterification rate which corresponded to 2% of normal LCAT activity; plasma LCAT protein concentration was 0.56 microg/ml and equivalent to approximately 10% of normal LCAT mass. Analysis by single strand conformation polymorphism (SSCP) of the PCR products corresponding to exons 4 and 5 of the LCAT gene revealed a visible band shift. Sequence analyses of exons 4 + 5 revealed two separate single point mutations: a C --> T transition replacing Arg147 by Trp and a T --> G transition converting Tyr171 to a stop codon. The presence of these two point mutations was confirmed by restriction enzyme analyses: the C --> T transition abolished a MwoI site whereas the T --> G transition created an AvrII site. The Arg147 mutation was associated with a non-secreted protein. The Tyr171 mutation resulted in formation of a truncated protein lacking the catalytic site. In summary, we have identified an LCAT deficient patient corresponding to a compound heterozygote for the Arg147 --> Trp mutation and a new molecular defect involving a Tyr171 --> Stop mutation in the LCAT gene.
Asunto(s)
Deficiencia de la Lecitina Colesterol Aciltransferasa/genética , Fosfatidilcolina-Esterol O-Aciltransferasa/genética , Mutación Puntual , Apolipoproteína A-I/metabolismo , Arginina , Colesterol/sangre , Ésteres del Colesterol/sangre , HDL-Colesterol/sangre , ADN/química , Femenino , Heterocigoto , Humanos , Deficiencia de la Lecitina Colesterol Aciltransferasa/sangre , Persona de Mediana Edad , Linaje , Fosfatidilcolina-Esterol O-Aciltransferasa/sangre , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Análisis de Secuencia de ADN , TirosinaRESUMEN
BACKGROUND: When routine blood chemistry shows elevated chloride alone, another anion (bromide, iodine, fluoride) may be involved. CASE REPORTS: Hyperchloremia and decreased anion gap was observed in four patients. Chloremia ranged from 134 to 174 mmol/l at initial blood tests. Careful history taking led to the discovery of long-term use of calcium bromogalacto-glucomate. Specific assay with inductively coupled plasma mass spectrometry (ICPMS) confirmed the presence of bromide in the blood. Chloridemia returned to normal levels after discontinuing use of bromine. DISCUSSION: Bromism is not a common diagnosis. Risks include neurological and psychiatric disorders due to bromide diffusion through the blood-brain barrier. Clinical manifestations have been described including skin lesions, digestive intolerance, and fever. Bromide is contained in certain prescription drugs. Patients should be warned against the adverse effects of overuse.
Asunto(s)
Bromuros/envenenamiento , Cloruros/sangre , Adulto , Anciano , Bromuros/sangre , Femenino , Humanos , Persona de Mediana EdadAsunto(s)
Trasplante de Riñón/efectos adversos , Venas Renales/patología , Venas Renales/cirugía , Stents , Angioplastia/instrumentación , Constricción Patológica/diagnóstico por imagen , Constricción Patológica/cirugía , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Venas Renales/diagnóstico por imagenRESUMEN
A multicenter, prospective, and controlled trial was performed to evaluate the efficacy and tolerance of intravenous (i.v.) and subcutaneous (s.c.) recombinant erythropoietin (rH-EPO) administration routes in 49 long-term hemodialyzed patients on maintenance phase of treatment, to determine the usefulness of replacing i.v. route by SC route in all of them. Each of these patients had already been treated with rH-EPO by the i.v. route for at least 6 months and included in the protocol on stabilized consumption phase. We arbitrarily chose three strata according to previous needs: Stratum A (> 150 U/kg/week) for eight patients, Stratum B (100 to 150 U/kg/week) for 12 patients, and Stratum C (< 100 U/kg/week) for 29 patients. In each stratum, the further treatment route (i.v. or s.c.) was randomized. Finally, 25 patients continued with i.v. route, and the other 24 changed to the s.c. route. The objective was to maintain a stable hemoglobin level, ranging from 9 to 10 g/dL. Tolerance and consumption in each group (i.v. and s.c.) were compared 4 months later. Globally, for an identical efficacy, rH-EPO needs were lesser using s.c. route (84 U/kg/week) than i.v. route (112 U/kg/week) (P = 0.02). However, when the strata were studied, it transpires that this benefit existed only for consumers having the highest needs (Stratum A) and not for the others. With regard to tolerance, only thrombotic events might be less frequent by using s.c. route, but the significance threshold is not reached (P = 0.09). Thus, replacing i.v. route by SC route, especially in high consumers, reduces the cost of treatment by rH-EPO. This benefit might be dependent on previous needs.
Asunto(s)
Eritropoyetina/administración & dosificación , Diálisis Renal , Adulto , Anciano , Eritropoyetina/efectos adversos , Femenino , Hemoglobinas/análisis , Humanos , Inyecciones Intravenosas/efectos adversos , Inyecciones Subcutáneas/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Recombinantes/administración & dosificaciónRESUMEN
By analogy with desmoid tumours, tamoxifen has been used in the treatment of idiopathic retroperitoneal fibrosis. The authors report the 6th case of retroperitoneal fibrosis treated by tamoxifen alone, which had not recurred 11 months after stopping treatment.
Asunto(s)
Antagonistas de Estrógenos/uso terapéutico , Fibrosis Retroperitoneal/tratamiento farmacológico , Tamoxifeno/uso terapéutico , Adulto , Antagonistas de Estrógenos/administración & dosificación , Estudios de Seguimiento , Humanos , Masculino , Inducción de Remisión , Tamoxifeno/administración & dosificaciónRESUMEN
We have previously shown that human B lymphocytes cultured in the CD40 system, composed of an anti-CD40 mAb presented by a CD32-transfected fibroblastic cell line, proliferate but do not secrete immunoglobulins (Igs). However, the addition of particles of Staphylococcus aureus Cowan (SAC) induces B cell to secrete considerable amounts of Igs even in the absence of exogenous cytokines (CD40/SAC system). Additionally, B lymphocytes cultured in the CD40 system in the presence of human IL-10, produce high level of IgM, IgG and IgA, which are further increased by addition of SAC. Here, we have studied the capacity of peripheral blood lymphocytes from patients with IgA deficiency (IgA-D) to secrete Igs, particularly IgA after CD40 triggering. Peripheral blood mononuclear cells (PBMNC) from IgA-D patients cultured in the CD40/SAC system produced IgM and IgG, but no IgA. The addition of IL-10 to the cultures, enhanced the production of IgM and IgG and most strikingly induced the production of high amounts of IgA. The addition of IL-10 to PBMNC from IgA-D patients activated through CD40 alone resulted in the production of IgA. Thus, IL-10 can remove the block in B cell differentiation and allows B cells from IgA-D patients to differentiate into IgA secreting cells.
Asunto(s)
Linfocitos B/inmunología , Deficiencia de IgA/inmunología , Inmunoglobulina A/biosíntesis , Interleucina-10/farmacología , Adulto , Antígenos CD40/inmunología , Células Cultivadas , Femenino , Humanos , Inmunoglobulina G/biosíntesis , Inmunoglobulina M/biosíntesis , Activación de Linfocitos , Masculino , Staphylococcus aureus/inmunologíaAsunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antígenos CD4/inmunología , Rechazo de Injerto/prevención & control , Trasplante de Riñón/inmunología , Receptores de Interleucina-2/inmunología , Corticoesteroides/uso terapéutico , Adulto , Antígenos CD/inmunología , Azatioprina/uso terapéutico , Transfusión Sanguínea , Creatinina/metabolismo , Ciclosporina/uso terapéutico , Femenino , Humanos , Inmunoglobulina G/uso terapéutico , Terapia de Inmunosupresión/métodos , Trasplante de Riñón/fisiología , Masculino , Persona de Mediana Edad , Proyectos Piloto , Resultado del TratamientoAsunto(s)
Azatioprina/efectos adversos , Glomerulonefritis por IGA/cirugía , Trasplante de Riñón/inmunología , Metiltransferasas/deficiencia , Pancitopenia/inducido químicamente , Adulto , Azatioprina/farmacocinética , Eritrocitos/enzimología , Femenino , Glomerulonefritis por IGA/enzimología , Glomerulonefritis por IGA/genética , Homocigoto , Humanos , Masculino , Mercaptopurina/sangre , Mercaptopurina/farmacocinética , Metiltransferasas/sangre , Metiltransferasas/genética , Linaje , Tioguanina/análisisRESUMEN
We have previously shown that human B lymphocytes cultured in the CD40 system, composed of an anti-CD40 mAb presented by a CD32-transfected fibroblastic cell line, proliferate but do not secrete antibodies. However, the addition of particles of Staphylococcus aureus Cowan (SAC) induces B cell differentiation even in the absence of exogenous cytokines (CD40/SAC system). Additionally, B lymphocytes cultured in the CD40 system in the presence of human IL-10, produce IgM, IgG, and IgA, and Ig levels are further increased by SAC. Here, we have studied the capacity of peripheral blood lymphocytes from patients with IgA deficiency (IgA-D) to secrete Igs, particularly IgA after CD40 triggering. Peripheral blood mononuclear cells (PBMNC) from IgA-D patients cultured in the CD40/SAC system produced IgM and IgG, but not IgA. The addition of IL-10 to the cultures, enhanced the production of IgM and IgG and most strikingly induced the production of high amounts of IgA. The addition of IL-10 to PBMNC from IgA-D patients activated through CD40 alone resulted in the production of IgA. Thus, SAC and anti-CD40 mAb stimulate B cells to differentiate into cells secreting IgG and IgM whereas IL-10 plays a central role in inducing B cells from IgA-D patients to differentiate into IgA secreting cells.
Asunto(s)
Linfocitos B/efectos de los fármacos , Deficiencia de IgA/inmunología , Inmunoglobulina A Secretora/metabolismo , Interleucina-10/farmacología , Adolescente , Adulto , Anticuerpos Monoclonales/inmunología , Antígenos CD/fisiología , Antígenos de Diferenciación de Linfocitos B/fisiología , Linfocitos B/inmunología , Antígenos CD40 , Células Cultivadas , Niño , Preescolar , Femenino , Humanos , Inmunofenotipificación , MasculinoAsunto(s)
Trasplante de Riñón/diagnóstico por imagen , Tecnecio Tc 99m Mertiatida , Adolescente , Adulto , Creatinina/sangre , Estudios de Evaluación como Asunto , Femenino , Humanos , Pruebas de Función Renal/métodos , Trasplante de Riñón/fisiología , Masculino , Persona de Mediana Edad , Cintigrafía , Valores de ReferenciaAsunto(s)
Deficiencia de IgA/etiología , Inmunoglobulina A/análisis , Trasplante de Riñón/inmunología , Adulto , Infecciones por Citomegalovirus/inmunología , Femenino , Supervivencia de Injerto , Hepatitis B/inmunología , Humanos , Deficiencia de IgA/sangre , Inmunoglobulina A/sangre , Terapia de Inmunosupresión/métodos , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Saliva/inmunología , Factores de TiempoRESUMEN
Depressed immunity in uremic patients increases by ten the risk of tuberculosis. In such patients, 40% of tuberculosis manifestations are extrapulmonary, and peritoneum is involved in about 6% of the cases. Seventeen cases of peritoneal tuberculosis have been so far reported in CAPD patients, and we add a new case. The prognosis of the disease is severe since 8 patients died. Three deaths out of 8 are directly linked to tuberculosis. Indeed, peritoneal tuberculosis diagnosis is hard and often late, at least for two main reasons: at first, it can be difficult to exclude the other causes of lymphocytic peritonitis (viral, fungal, bacterial, etc.), secondly, growth of mycobacteria in dialysate effluent cultures is late and inconstant. Omental biopsy in lymphocytic peritonitis of unknown origin could be of great value for an early diagnosis. Despite the adaptation of antituberculous drugs doses, side-effects are not so rare: optical neuritis and liver toxicity in our case. In spite of ultrafiltration loss, stopping CAPD is not always necessary, as in the reported case.