[Recurrent vascular access trombosis associated with the prothrombin mutation G20210A in a adult patient in haemodialysis]. / Trombosis recurrente del acceso vascular asociada a la mutación G202 10A del gen de la protrombina en un paciente adulto en hemodiálisis.

Vascular access-related complications are a frequent cause of morbidity in haemodialysis patients and generate high costs. We present the case of an adult patient with end-stage renal disease and recurrent vascular access thrombosis associated with the prothrombin mutation G20210A and renal graft intolerance. The clinical expression of this heterozygous gene mutation may have been favoured by inflammatory state, frequent in dialysis patients. In this patient, the inflammatory response associated with the renal graft intolerance would have favored the development of recurrent vascular access thrombosis in a adult heterozygous for prothrombin mutation G20210A. In the case of early dysfunction of haemodialysis vascular access and after ruling out technical problems, it is convenient to carry out a screening for thrombophilia.

Trombosis recurrente del acceso vascular asociada a la mutación G20210A del gen de la protrombina en un paciente adulto en hemodiálisis / Recurrent vascular access trombosis associated with the prothrombin mutation G20210a in a adult patient in haemodialysis

Las complicaciones relacionadas con el acceso vascular (AV) son una causa frecuentede morbilidad de los pacientes en hemodiálisis (HD) y generan un elevadocoste. Presentamos el caso de un paciente adulto con insuficiencia renal crónicaterminal y trombosis repetidas del AV para hemodiálisis, asociado a lamutación G20210A del gen de la protrombina, en el contexto de una intoleranciaa un injerto renal no funcionante. La expresión clínica de este tipo de alteracionesde la coagulación, puede estar favorecida en el paciente en HD, por lapresencia de un estado inflamatorio, frencuente en estos pacientes. En este caso,la respuesta inflamatoria asociada a la intolerancia al injerto renal podría haberfavorecido la manifestación clínica en forma de trombosis de repetición del AV enun paciente heterocigoto para la mutación G20210A del gen de la protrombina.En los pacientes que desarrollan disfunción precoz del AV y no presentan problemasen la técnica de implantación, debe estudiarse la existencia de un estadoprotrombótico

Vascular access-related complications are a frequent cause of morbidity in haemodialysispatients and generate high costs. We present the case of an adult patient withend-stage renal disease and recurrent vascular access thrombosis associated with theprothrombin mutation G20210A and renal graft intolerance. The clinical expression of this heterozygous gene mutation may have been favoured by inflammatory state, frequentin dialysis patients. In this patient, the inflammatory response associated withthe renal graft intolerance would have favored the development of recurrent vascularaccess thrombosis in a adult heterozygous for prothrombin mutation G20210A. In thecase of early dysfunction of haemodialysis vascular access and after ruling out technicalproblems, it is convenient to carry out a screening for thrombophilia

[Cytomegalovirus esophagitis in a patient on peritoneal dyalisis]. / Esofagitis por citomegalovirus en un paciente en diálisis peritoneal.

Symptomatic cytomegalovirus (CMV) infection usually affects immunocompromised patients, such as transplant recipients. From that point of view, the patient with endstage renal disease under maintenance dialysis is considered as immunocompetent. Thus, opportunistic infections, such as CMV infection, is not systematicaly searched in these patients, despite that an impaired cellular immunity has been reported in dialysis patients. We report a case of CMV esophagitis, clinically symptomatic, in a patient endstage renal disease under peritoneal dialysis, without other known immunosuppressive factors and with a good clinical response to gancyclovir treatment.

Esofagitis por citomegalovirus en un paciente en diálisis peritoneal / Cytomegalovirus esophagitis in a patient on peritoneal dyalisis

La infección por citomegalovirus (CMV) clínicamente sintomática se presenta habitualmenteen personas severamente inmunocomprometidas, como los pacientestransplantados. Desde ese punto de vista, se ha considerado clásicamente al pacientecon insuficiencia renal crónica (IRC) en diálisis como «inmunocompetente».Por ello, las infecciones por gérmenes oportunistas, como el CMV, no son investigadassistemáticamente en este tipo de enfermos, a pesar de haberse demostradoalteraciones en la inmunidad celular en los pacientes en diálisis.Presentamos un caso de esofagitis por CMV, clínicamente sintomática, en un pacientecon IRC en diálisis peritoneal (DP), sin otros factores clásicos de inmunosupresióny con buena respuesta al ganciclovir

Symptomatic cytomegalovirus (CMV) infection usually affects immunocompromisedpatients, such as transplant recipients. From that point of view, the patientwith endstage renal disease under maintenance dialysis is considered as immunocompetent.Thus, opportunistic infections, such as CMV infection, is not systematicalysearched in these patients, despite that an impaired cellular immunity hasbeen reported in dialysis patients.We report a case of CMV esophagitis, clinically symptomatic, in a patient endstagerenal disease under peritoneal dialysis, without other known immunosuppressivefactors and with a good clinical response to gancyclovir treatment

[Superior vena cava thrombosis in a patient on hemodialysis]. / Trombosis de la vena cava superior en un paciente en hemodiálisis.

We present a patient with end-stage renal disease on maintenace hemodialysis through a permanent catheter (Permcath) on the right subclavian vein. One month after the catheter placement the patient exhibited a superior vena cava syndrome due to a pericatheter thrombosis. The patient was initially managed with anticoagulation with early clinical improvement. Nevertheless, the reappearance of the symptoms forced the removal of the catheter and percutaneous angioplasty of the superior vena cava. After those measures and anticoagulation with coumarin the patient remains stable with complete clinical resolution and angiographical improvement.

Trombosis de la vena cava superior en un paciente en hemodiálisis / Superior vena cava thrombosis in a patient on hemodialysis

Presentamos el caso de un paciente con insuficiencia renal crónica terminal en programa de hemodiálisis crónica a través de un catéter Permcath® subclavio derecho, que presentó un síndrome de la vena cava superior (VCS) a consecuencia de una trombosis pericatéter que se trató inicialmente de manera conservadora mediante anticoagulación con mejoría inicial. Por reaparición de la clínica debió finalmente procederse a la retirada del Permcath®, angioplastia de la VCS y continuar la anticoagulación con dicumarínicos, con resolución clínica del cuadro y mejoría radiológica (AU)

We present a patient with end-stage renal disease on maintenace hemodialysis through a permanent catheter (Permcath®) on the right subclavian vein. One month after the catheter placement the patient exhibited a superior vena cava syndrome due to a pericatheter thrombosis. The patient was initially managed with anticoagulation with early clinical improvement. Nevertheless, the reappearance of the symptoms forced the removal of the catheter and percutaneous angioplasty of the superior vena cava. After those measures and anticoagulation with coumarin the patient remains stable with complete clinical resolution and angiographical improvement (AU)

[Uremic media affects hemostatic properties of human endothelial cells in culture and increases the production of von Willebrand factor]. / El medio urémico altera las propiedades hemostáticas de células endoteliales humanas en cultivo y aumenta la producción de factor von Willebrand.

We have investigated the ability of serum from uremic patients to modify the thrombogenic properties of the endothelium. The effect of the uremic media on the morphology of ECs, and their resistance to flow was analyzed. The reactivity of the extracellular matrix (ECM) generated by ECs towards normal platelets was evaluated in a parallel-plate perfusion chamber. Exposure of ECs to uremic media resulted in abnormal morphology and signs of accelerated growth. Detachment of ECs exposed to circulating blood was increased when cells had been grown with media supplemented with uremic serum (22% vs 13%). Platelet deposition and formation of aggregates were significantly elevated on ECMs generated in the presence of uremic media (40.23 +/- 6.43% vs 25.42 +/- 2.69%, p < 0.05, n = 5). Immunocytochemical methods detected an enhanced expression of von Willebrand factor antigen on uremic ECMs (uremic 17.1 +/- 4.2% vs control 13.57 +/- 3.98%, p < 0.05) and its mRNA expression in endothelial cells (uremic 213.24 +/- 6.13 vs control 200.77 +/- 7.52, p < 0.05). These results suggest that uremic medium alters endothelial function and impairs the antithrombotic functions of cultured endothelial cells. This effect may contribute to the increased cardiovascular and thrombotic risk reported in ESRD patients.

El medio urémico altera las propiedades hemostáticas de células endoteliales humanas en cultivo y aumenta la producción de factor von Willebrand / Uraemic medium alters endothelial function and increases the thrombogenicity and von Willebrand factor expression of the extracellular matrix

El objetivo de este estudio fue determinar la capacidad del suero urémico de modificar las propiedades hemostáticas del endotelio. Para ello se analizó el efecto del medio urémico sobre la morfología y resistencia al flujo de las células endoteliales, así como la trombogenicidad de la matriz subendotelial generada por las células endoteliales.La exposición de células endoteliales en cultivo a un suero urémico indujo alteraciones en su morfología y un crecimiento acelerado de las mismas.Cuando las células endoteliales en cultivo eran expuestas a sangre circulante el desprendimiento de las mismas era superior cuando fueron cultivadas en suero urémico (22 por ciento vs 13 por ciento). La adhesión de plaquetas y la formación de agregados eran superiores en las matrices subendoteliales generadas en presencia de medio urémico (40,23 ñ 6,43 por ciento vs 25,42 ñ 2,69 por ciento, p < 0,05, n = 5).Asimismo, se detectó un aumento en la expresión de antígeno del factor von Willebrand mediante métodos inmunocitoquímicos en las matrices subendoteliales urémicas (17,1 ñ 4,2 por ciento vs 13,57 ñ 3,98, p < 0,05) y la de la expresión de su ARNm en células endoteliales (213,24 ñ 6,13 vs 200,77 ñ 7,52, p < 0,05).Estos resultados indican que el medio urémico altera la función endotelial in vitro y aumenta la trombogenicidad del subendotelio. Estos cambios podrían estar implicados en el aumento del riesgo cardiovascular y de sufrir fenómenos trombóticos que presentan los pacientes con insuficiencia renal crónica. (AU)

Uremic medium disturbs the hemostatic balance of cultured human endothelial cells.

We have investigated the ability of serum from uremic patients to modify the thrombogenic properties of the endothelium. The effects of uremic medium on the morphology of endothelial cells (ECs), and their resistance to flow was analyzed. The influence of uremic media on the reactivity of the extracellular matrix (ECM) generated by ECs towards normal platelets was evaluated in a parallel-plate perfusion chamber. Exposure of ECs to uremic medium resulted in abnormal cell morphology and signs of an accelerated growth. Detachment of ECs exposed to circulating blood was increased when cells had been grown with media supplemented with uremic serum (21% vs. 14% non exposed). Platelet deposition was significantly elevated on ECMs generated in the presence of uremic media (uremicECMs) (p<0.01 vs. control studies). Effects of uremic serum were not observed at short incubation periods (5 h) but were evident after 24 or 72 h of incubation. Northern blot analysis revealed increased expression of tissue factor (TF) mRNA in ECs exposed to uremic conditions. Immunocytochemical methods detected an augmented expression of TF antigen on uremic ECMs. Incubation of ECMs with an antibody to human tissue factor prevented the increase in platelet deposition observed in uremic ECMs, suggesting that the presence of TF in ECM could be responsible for the enhanced platelet deposition. Results from our study indicate that uremic medium impairs the antithrombotic functions of cultured endothelial cells.

[Vascular access in Spain: analysis of its distribution, morbidity, and monitoring systems]. / El acceso vascular en España: análisis de su distribución, morbilidad y sistemas de monitorización.

Vascular access disfunction causes a therapeutic emergency with different implications in patients and care givers. The aim of this study was to know the distribution of different kinds of vascular access between prevalent hemodialysis patients, the proportion of incident patients that holds a permanent vascular access, the monthly hospital ratio for access repair and the use of surveillance systems of vascular access adequacy in the different Centers. This is a National survey that shows results of a questionnaire sent to all hemodialysis units in Spain on september 1999. Eighty-eight units answered the questionnaire (42%) providing information about 5,476 prevalent patients. Of these patients, 81% receives treatment through an arteriovenous fistula, 10% uses a central catheter and 9% a graft. Only 56% of incident patients have a permanent vascular access. Reasons for catheter use between prevalent patients were exhaustion of vascular sites in 42%, maduration of permanent access in 24%, thrombosis of the access in 14% and another reasons in 19%. Patients monthly hospitalization ratio for vascular repair was 3%, that might represent more than 5,600 hospital ingress by year. More than 80% of the Units releases different surveillance programs of access adequacy, 69% by fiscal detection problems, 47% by dynamic alterations and 18% by dilution and imaging procediments. The conclusions of this survey are that arteriovenous fistula is the most used vascular access in Spain. Almost half of the patients do not have vascular access in use for the beginning of hemodialysis. Exhausted vascular sites is the primary reason for central catheter using. A great proportion of Units are employing programs for access monitoring.

El acceso vascular en españa: análisis de su distribución, morbilidad y sistemas de monitorización / Vascular access in Spain: distribution, morbidity and surveillance systems

La disfunción del acceso vascular constituye una emergencia terapéutica que ocasiona diferentes tipos de repercusión entre pacientes y profesionales.El objetivo del presente estudio es el de conocer la distribución de las diferentes modalidades de acceso vascular entre la población en programa de hemodiálisis periódicas en España, la proporción de enfermos que disponen de un acceso vascular permanente en el momento de iniciar el tratamiento, la tasa de ingresos hospitalarios que originan las complicaciones del acceso vascular y la implantación de sistemas de monitorización sobre la función del mismo.Se analizan los datos de un cuestionario remitido a todas las Unidades de Diálisis según censo de un catálogo internacional y se obtienen los siguientes resultados: sobre una muestra de 5.472 pacientes el 81 por ciento se dializan mediante una fístula arteriovenosa, el 10 mediante un catéter y un 9 por ciento emplea un injerto. El 44 por ciento de los pacientes no disponen de acceso vascular permanente en el momento de iniciar el tratamiento. El 42 por ciento de los pacientes que emplea catéteres es debido al agotamiento de la red venosa para proceder a la implantación de nuevos accesos, un 24 por ciento porque su fístula está en período de maduración, un 14 por ciento porque su acceso se ha trombosado y está pendiente de reparación y un 19 por ciento por otras razones. La tasa de ingresos para reparar disfunciones es del 3 por ciento de pacientes/mes lo que representa más de 5.600 hospitalizaciones a nivel nacional por este concepto. El 80 por ciento de las Unidades realiza monitorización sistemática del funcionamiento del AV: 69 por ciento emplea parámetros físicos, el 47 por ciento dinámicos y el 18 por ciento técnicas de imagen y dilución.El 71 por ciento de las Unidades utiliza al menos un sistema de monitorización, más del 50 por ciento de las Unidades utiliza dos sistemas conjuntos, y un 9 por ciento realiza los tres sistemas de control.Se concluye del presente estudio que la fístula arteriovenosa es el acceso vascular que se utiliza de forma preferente en España. Cerca de la mitad de los pacientes no disponen de acceso permanente en el momento de iniciar la hemodiálisis. El agotamiento de la red venosa es la causa más frecuente de la utilización de catéteres. La disfunción del acceso provoca una tasa significativa de ingresos.La Mayoría de las Unidades del país emplean sistemas de monitorización del acceso vascular. (AU)

[Increased adrenomedullin levels in hypertensive patients on maintenance hemodialysis]. / Niveles elevados de adrenomedulina en pacientes hipertensos en programa de hemodiálisis.

Hypertension is a frequent finding in uremic patients. The pathogenesis of this complication in uremia is complex and not fully elucidated. An imbalance between the vasoconstrictor and vasodilator systems may be involved in its pathogenesis. In this study we have evaluated the state of nitric oxide (NO) and adrenomedullin (ADM) in hemodialyzed patients, especially those with hypertension. We included a group of hypertensive hemodialyzed patients (n = 9) and a group of normotensive control patients (n = 10). We measured plasma renin activity, as well as plasma catecholamines, ADM, and nitrite/nitrate levels in basal conditions before starting the hemodialysis session. Plasma volume, as well as left ventricular ejection fraction were also measured. Hemodialysis patients showed plasma levels of nitrite/nitrates and ADM higher than the reference values in the normal population. We observed no differences in the plasma levels of nitrite/nitrates, but ADM levels were higher in hypertensive (278.2 +/- 15.5 pg/ml) patients than in normotensive patients (225 +/- 9.9 pg/ml) (p < 0.05). When considering all patients together, mean arterial pressure positively correlated with plasma ADM (r = 0.468, p < 0.05). Plasma volume and left ventricular ejection fraction were similar in the two groups of patients. In summary, plasma levels of nitrite/nitrates and ADM are increased in hemodialyzed patients, although only ADM levels were further increased in hypertensive patients. Our results do not suggest that a decreased production in the vasodilator factors evaluated is involved in the pathogenesis of hypertension in uremic patients.

Estatus epiléptico no convulsivo secundario a cefepima a dosis ajustadas en enfermos con insuficiencia renal crónica / Non-convulsive epileptic status after administration of cefepime in patients with advanced chronic renal failure

El síndrome febril es uno de los principales motivos de ingreso hospitalario en pacientes con insuficiencia renal crónica. En algunos casos se presentan sin focalidad clínica evidente y la falta de respuesta al tratamiento empírico inicial obliga al cambio por otros antibióticos de más amplio espectro. La disponibilidad de cefalosporinas de cuarta generación (cefepima) y la frecuencia creciente de resistencias microbianas a antibióticos más antiguos hace que el uso de estas sea cada día más frecuente en el medio hospitalario. Presentamos dos casos clínicos de estatus epiléptico no convulsivo en pacientes con insuficiencia renal que recibieron cefepima a dosis corregidas para el grado de función renal segón posología recomendada por el laboratorio. El cuadro neurológico debutó en forma de bradipsiquia, desorientación, déficit de atención y posterior aparición de movimientos mioclónicos. En los dos casos el electroencefalograma (EEG) presentaba un patrón compatible con estatus epiléptico no convulsivo. El cuadro clínico remitió y se normalizó el EEG en ambos casos tras la retirada del antibiótico. Una revisión de la literatura sobre la farmacocinética de cefepima indica que las dosis aconsejadas en la ficha técnica del fármaco son posíblemente demasiado elevadas en pacientes con insuficiencia renal avanzada. Concluimos que el tratamiento con cefepima en pacientes con insuficiencia renal avanzada puede desencadenar un estatus epiléptico no convulsivo. Es urgente que los estudios farmacocinéticos aclaren definitivamente la posología de este fármaco en este grupo de pacientes (AU)

Niveles elevados de adrenomedulina en pacientes hipertensos en programa de hemodiálisis / Increased plasma adrenomedullin levels in patients with end-stage renal disease on maintenance hemodialysis: role of hypertension

Los pacientes urémicos presentan con frecuencia hipertensión arterial cuyo origen es multifactorial y no bien dilucidado. Un disbalance entre la actividad de los sistemas presores y vasodilatadores podría estar implicado en su patogenia. En este trabajo nos hemos propuesto valorar el estado del óxido nítrico (NO) y la adrenomedulina (ADM) en pacientes hemodializados con hipertensión arterial. Estudiamos un grupo de pacientes hemodializados hipertensos (n = 9) y un grupo de pacientes normotensos (n = 10) controles. A estos pacientes se les determinó la actividad renina plasmática (ARP), así como niveles plasmáticos de catecolaminas, ADM, nitritos/nitratos (para estimar la producción de NO) en condiciones basales, antes de iniciar la sesión de hemodiálisis. Los niveles plasmáticos cite catecolaminas y ARP eran similares en ambos grupos de pacientes. Los pacientes hemodializados en conjunto presentaban unos niveles de nitritos/nitratos y de ADM superiores a los valores de referencia en la población general. No se observaron diferencias significativas en los niveles de nitritos/n¡tira tos, pero los niveles de ADM eran superiores en los pacientes hipertensos (278,3 ñ 15,5 pg/ml) respecto a los normotensos (224,9 ñ 9,9 pglml) (p < 0;01). Considerando a todos los pacientes en conjunto observamos una correlación positiva entre niveles adrenomedulina y niveles de presión arterial diastólica (r = 0,51, p < 0,05) y media (r = 0,468, p = 0,05).En conclusión, los niveles de ADM y nitritoslnitratos están elevados en los pacientes en HD, aunque sólo los niveles de ADM eran superiores en los pacientes hipertensos. Nuestros resultados no sugieren que un descenso de la liberación de factores vasodilatadores estén implicados en la HTA del paciente urémico (AU)

Abnormal platelet cytoskeletal assembly in hemodialyzed patients results in deficient tyrosine phosphorylation signaling.

BACKGROUND: Uremic patients have a bleeding tendency associated with a platelet dysfunction. We evaluated the impact of a repeated hemodialysis procedure on primary hemostasis by analyzing different aspects of platelet activation in uremic patients. METHODS: Studies were performed in (1) eight patients with end-stage renal disease before the hemodialysis program was initiated and after initiating hemodialysis treatment, and in (2) eight patients on maintenance hemodialysis who were transferred to continuous ambulatory peritoneal dialysis. Studies included routine platelet aggregations and evaluation of platelet-subendothelium interactions under flow conditions. Contractile proteins and tyrosine phosphorylation associated with the cytoskeleton were analyzed, before and after thrombin activation of platelets, by electrophoresis after Triton X-100 extraction. RESULTS: No changes in the clinical parameters analyzed were observed among the different study groups. Aggregation and platelet adhesion only improved when patients were shifted from hemodialysis to continuous ambulatory peritoneal dialysis (P < 0.05 for both percentage of surface covered by platelets and aggregate formation). The association of cytoskeletal proteins in platelets from patients under hemodialysis treatment was statistically decreased with respect to the corresponding values in platelets from patients not subjected to dialysis (P < 0.01 for actin). However, after two months on peritoneal dialysis, these values increased to almost control values (P < 0.001 for actin, vs. hemodialysis). Similarly, translocation of tyrosine-phosphorylated proteins to the cytoskeletal fraction was impaired in platelets from hemodialyzed patients, and it recovered partially after the patients transferred to continuous ambulatory peritoneal dialysis. CONCLUSIONS: Our present data support the concept that repeated platelet stress during hemodialysis has a deleterious effect on the organization of platelet cytoskeleton, which seems to impair the translocation of signal transduction proteins within platelets compromising the platelet function in uremia.

Increased plasma adrenomedullin levels in hemodialysis patients with sustained hypotension.

BACKGROUND: Sustained hypotension in end-stage renal disease patients is characterized, despite an overactivation of the sympathetic and renin-angiotensin systems, by decreased vascular resistance and a blunted vascular response to pressor stimuli. An increased production of one or more vasodilator substances might play a role in the reduced vascular resistance and response to pressor stimuli in these patients. We evaluated the possible role of an increased production of nitric oxide and/or adrenomedullin (ADM) in the pathophysiology of chronic hypotension in hemodialysis (HD) patients. METHODS: Three groups of hypotensive (N = 9), normotensive (N = 10), and hypertensive (N = 9) HD patients were included in the study. Plasma renin activity (PRA) and plasma levels of catecholamines, ADM, nitrite/nitrate (an estimator of nitric oxide production), tumor necrosis factor (TNF), and interleukin-1beta (IL-1beta) were measured. Plasma volume and left ventricular ejection fraction (LVEF) were also evaluated. RESULTS: Plasma levels of nitrite/nitrate and ADM were elevated in HD patients with respect to the reference values in normal subjects. Plasma ADM levels, but not nitrite/nitrate levels, were higher in hypotensive (368.1 +/- 25.4 pg/mL) than normotensive (225 +/- 9.9 pg/mL) and hypertensive HD patients (278.2 +/- 15.5 pg/mL, P < 0.01). When considering hypotensive and normotensive patients together, the mean blood pressure inversely correlated with time on HD (r = -0. 53, P < 0.05) and plasma ADM levels (r = -0.78, P < 0.01). CONCLUSIONS: Plasma ADM and nitrite/nitrate levels are increased in HD patients, but only ADM levels were higher in hypotensive than in normotensive and hypertensive HD patients. The higher plasma levels of this peptide in hypotensive patients and its inverse correlation with mean arterial pressure suggest that ADM may be involved in the pathophysiology of chronic hypotension in HD patients.

[Non-convulsive status epilepticus secondary to adjusted cefepime doses in patients with chronic renal failure]. / Estatus epiléptico no convulsivo secundario a cefepima a dosis ajustadas en enfermos con insuficiencia renal crónica.

Fever is one of the most frequent causes of hospital admission in patients with end-stage renal disease. Lack of an identified source of infection and/or lack of clinical response to the first empirical antibiotic treatment favour the use of broader spectrum antibiotics. The availability of fourth-generation cephalosporins (e.g. cefepime) and the increasing incidence of bacterial resistances to classical antibiotics has increased their use in the clinical practice. We present two cases of non-convulsive status epilepticus in patients with advanced chronic renal failure who received cefepime at doses corrected for the degree of renal function according to the manufacturer's instrument as. The clinical symptoms included shouthough, processes, disorientation, loss of attention, and the later appearance of myoclonus. In both cases the electroencephalogram (EEG) was compatible with non-convulsive epileptic status. After cefepime withdrawal there was a clinical remission of symptoms and normalization of the EEG. It is concluded that cefepime treatment can induce a non-convulsive epileptic status in patients with advanced chronic renal failure. Pharmacokinetic studies are urgently needed to clearly define the appropriate dose of cefepime in patients with advanced chronic renal failure.

Erythropoietin improves signaling through tyrosine phosphorylation in platelets from uremic patients.

Erythropoietin has shown to be effective in the correction of the hemostatic defect present in uremic patients. We have investigated the possible effect of recombinant human erythropoietin (rHuEPO) on the signaling processes occurring in platelets. Platelet suspensions were obtained from hemodialyzed patients before and after at least one month of initiating treatment with rHuEPO. Aliquots of non-activated or thrombin-activated platelets were treated to obtain platelet lysates or processed to extract platelet cytoskeleton. Samples were resolved by 8% SDS-polyacrylamide gel electrophoresis followed by Western blotting. After thrombin activation, proteins p120, p85, p78, p75, pp62, pp60, p59, p58, p56, p54 and p52 associated with the Triton-insoluble cytoskeletal fraction appeared phosphorylated in control profiles. In profiles from platelets obtained from uremic patients before treatment with rHuEPO, only proteins p58 and p56 appeared clearly and p54 was slightly phosphorylated. However, in platelets from the same patients under rHuEPO treatment, thrombin-induced phosphorylation improved to levels even above those observed in control profiles. Specially, the band at 54KDa appeared consistently more phosphorylated in all the patients under rHuEPO treatment. Although it is accepted that part of the hemostatic effect of erythropoietin is mediated by an increase in hematocrit, our study suggests that it enhances platelet signaling in uremic platelets which may explain the improvement of platelet response to activating stimulus before clinically noticeable elevation of hematocrit.

Hepatitis G virus infection in a haemodialysis unit: prevalence and clinical implications.

BACKGROUND: Hepatitis viruses have become one of the main infectious problems in patients on long-term haemodialysis. A new RNA virus, designated hepatitis G virus (HGV) has been recently identified. The pathogenic relevance of this virus is currently under investigation. The aim of this study was to analyse the prevalence and clinical implications of hepatitis G virus infection in patients on haemodialysis. METHODS: The presence of HGV-RNA was investigated in 96 patients on maintenance haemodialysis. Hepatitis viral markers (HBsAg, anti-HCV, HGV-RNA) and liver tests were assessed in all these patients, as well as the risk factors for hepatitis viruses acquisition. As a control group, 200 blood donors were tested for the presence of HGV-RNA. RESULTS: HGV-RNA was detected in 25 of 96 patients on haemodialysis (26%) and in six of 200 blood donors (3%) (P < 0.001). Thirteen of 25 HGV infected patients (52%) were coinfected with other hepatitis viruses (HBV and/or HCV). Evidences of chronic liver disease were more frequent in patients infected by HBV and/or HCV (61%) than in patients infected by HGV alone (17%) (P = 0.01). Although 80% of HGV infected patients had received blood products, the transfusion rate was not different from non HGV-infected patients. Time on haemodialysis was significantly shorter in patients infected with HGV alone (3.1 +/- 3.5 years) compared to patients infected with HBV and/or HCV (7.6 +/- 5.8 years) (P = 0.04). CONCLUSIONS: Patients on maintenance haemodialysis are at increased risk for HGV infection. HGV infection itself does not seem to be a frequent cause of chronic liver disease in these patients. Since the prevalence of HGV infection in blood donors is high, blood transfusion could be one of the main factors implicated in HGV transmission in patients on haemodialysis.