RESUMEN
BACKGROUND: Solid organ transplant recipients undergoing immunosuppressive therapy are considered to be at high risk of serious infectious complications. In 2009, a new influenza pandemic caused serious infections and deaths, especially among children and immunocompromised patients. Herein we have reported the safety and efficacy of a single-shot monovalent whole-virus vaccine against H1N1 infection in the pediatric renal transplant population. METHODS: In November and December 2009, we vaccinated 37 renal transplant children and adolescents and measured their antibody responses. Seroprotection, seroconversion, and seroconversion factors were analyzed at 21 days after vaccination. RESULTS: None of the vaccinated patients experienced vaccine-related side effects. None of the patients had an H1N1 influenza infection after vaccination. All of the patients showed elevations in antibody titer at 21 days after vaccination. In contrast, only 29.72% of the patients achieved a safe seroprotection level and only 18.75% a safe seroconversion rate. More intense immunosuppressive treatment displayed negative effect on seroprotection and seroconversion, and antibody production significantly increased with age. No other factor was observed to influence seroprotection. CONCLUSIONS: We recommend vaccination of children and adolescent renal transplant recipients against H1N1 virus. However, a single shot of vaccine may not be sufficient; to achieve seroprotection, a booster vaccination and measurement of the antibody response are needed to assure protection of our patients.
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Inmunosupresores/efectos adversos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Trasplante de Riñón/efectos adversos , Adolescente , Anticuerpos Antivirales/sangre , Distribución de Chi-Cuadrado , Niño , Femenino , Humanos , Hungría , Inmunización Secundaria , Vacunas contra la Influenza/efectos adversos , Gripe Humana/inmunología , Gripe Humana/virología , Masculino , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Anatomical malformations of the kidney and urinary tract account for 17% of pediatric renal transplantation procedures. Heat shock proteins (HSPs) are molecular chaperones with a protective function that promotes cell survival. HSP72 is an endogenous ligand for toll-like receptor TLR4, thereby stimulating innate immunity. Both in adults and children, decreased expression of HSP70s is associated with a number of kidney diseases. OBJECTIVE: To assess the prevalence of HSPA1A G(190)C, HSPA1B A(1267)G, and TLR4 A(896)G polymorphisms in children who had undergone kidney transplantation. PATIENTS AND METHODS: Genotypes were analyzed using allele-specific polymerase chain reaction in 41 pediatric recipients. Allelic prevalence was related to reference values in 65 age- and sex-matched healthy children. RESULTS: Clinical data did not reveal a difference between any of the groups. HSPA1B (1267)GG genotype and HSPA1B (1267)G allele were observed more frequently in the transplant recipients compared with the control group: AA vs AG: odds ratio [OR], 12.6; 95% confidence interval [CI], 1.58-100.0; P = .004; AA vs GG: OR, 20.80; 95% CI, 2.32-187.00; P = .01; and A vs G: OR, 2.10; 95% CI, 1.19-3.07; P = .01. Furthermore, the prevalence of the HSPA1B (1267)GG genotype was greater in transplant recipients with vs without urinary tract malformations: AG vs GG: OR, 0.10; 95% CI, 0.09-0.48; P = .007. No differences were observed in the other studied polymorphisms. CONCLUSION: Our findings suggest an association between the carrier status of HSPA1B (1267)G with urinary tract malformations, leading to end-stage renal disease requiring kidney transplantation. This observation raises further questions about the clinical and therapeutic relevance of this polymorphism to pediatric nephrology.
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Proteínas HSP70 de Choque Térmico/genética , Proteínas de Choque Térmico/genética , Trasplante de Riñón/estadística & datos numéricos , Polimorfismo Genético , Sistema Urinario/anomalías , Adolescente , Adulto , Niño , Femenino , Frecuencia de los Genes , Genotipo , Proteínas del Choque Térmico HSP72/genética , Proteínas del Choque Térmico HSP72/metabolismo , Proteínas de Choque Térmico/sangre , Humanos , MasculinoRESUMEN
PTDM plays a role in chronic allograft nephropathy and decreases graft and patient survival. Considering the serious outcome of chronic hyperglycemia, the importance of early recognition and the few data in children, in this retrospective analysis we studied the characteristics and risk factors of PTDM in 45 pediatric renal transplant recipients receiving Tac or CyA-based immunosuppression. Fasting blood sampling and OGTT were performed. PTDM has been developed in six patients (13%), while seven children (16%) had IGT, with the overall incidence of a glucose metabolic disorder of 29% in pediatric renal transplants. Patients in the PTDM + IGT group were younger and had higher systolic blood pressure and serum triglyceride level than children with normal glucose tolerance. Multivariate analysis identified Tac treatment, Tac trough level, steroid pulse therapy and family history of diabetes to be associated with the onset of PTDM. In pediatric renal transplants, OGTT and frequent assessment of blood glucose levels might be essential not only in the post-transplant management, but also prior to transplantation, particularly with family history of diabetes. Careful monitoring and modified protocols help to minimize the side effects of Tac and corticosteroids.
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Diabetes Mellitus/etiología , Trasplante de Riñón/efectos adversos , Administración Oral , Adolescente , Adulto , Glucemia/metabolismo , Niño , Diabetes Mellitus/diagnóstico , Femenino , Humanos , Inmunosupresores/uso terapéutico , Enfermedades Renales/terapia , Masculino , Metilprednisolona/administración & dosificación , Esteroides/farmacología , Tacrolimus/efectos adversosRESUMEN
BACKGROUND: Low heart rate variability (HRV) is an independent risk factor of cardiac mortality in patients with end-stage renal disease (ESRD). It has been explained by uremic parasympathetic neuropathy. Sympathetic overactivity can also reduce HRV. Our aim was to determine whether there is vagal activity in ESRD patients that is masked by sympathetic activity. METHODS: The effect of propranolol on HRV was examined in 13 patients with ESRD, aged 20.1 +/- 7.6 years without diabetes. All patients were given intravenous propranolol (0.05 mg/kg) once and placebo once in a randomized, double-blind way, with an interval of 6.6 days (mean, range: 2-9). Propranolol was administered before hemodialysis treatment, after 40 minutes supine resting period. HRV was registered for 10 minutes, during supine, before and after the injection. Patients' HRV data were compared to that of 29 age-matched healthy controls. RESULTS: Initially, both high-(HFV) and low-frequency (LFV) bands of heart rate variability were lower in ESRD patients compared to controls (p < 0.001 for both). Propranolol resulted in a significant increase of HFV (propranolol: AlgHFV = 0.182 (0.027 - 0.337), placebo: deltalgHFV = -0.029 (-0.128 - +0.070); p = 0.032). Elevation of LFV was not significant. Six patients had an elevated plasma norepinephrine and/or epinephrine level. Plasma dopamine level was elevated in all but 1 patient (mean: 432 pmol/l, 95% CI: 320-543) and showed an inverse relationship with the increase of IgHFV secondary to propranolol (r = -0.66, p = 0.014). CONCLUSIONS: Low HFV of ESRD patients can be improved by beta-adrenergic blockade. It demonstrates that there is some vagal activity in ESRD that is masked by sympathetic activity. Therefore, altered sympathovagal balance of ESRD patients should be taken into consideration in the assessment of vagal uremic neuropathy.
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Antagonistas Adrenérgicos beta/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Fallo Renal Crónico/fisiopatología , Propranolol/farmacología , Adolescente , Adulto , Niño , Estudios Cruzados , Dopamina/metabolismo , Método Doble Ciego , Epinefrina/metabolismo , Femenino , Humanos , Fallo Renal Crónico/terapia , Masculino , Norepinefrina/metabolismo , Proyectos Piloto , Diálisis Renal , Sistema Nervioso Simpático/fisiología , Nervio Vago/fisiologíaAsunto(s)
Cápsula Articular/fisiopatología , Rango del Movimiento Articular , Proyectos de Investigación , Síndrome de Abducción Dolorosa del Hombro/fisiopatología , Adulto , Anciano , Ensayos Clínicos Controlados como Asunto , Femenino , Lateralidad Funcional , Humanos , Inestabilidad de la Articulación/fisiopatología , Masculino , Persona de Mediana Edad , Selección de PacienteRESUMEN
Hemodialysis (HD) causes rapid volume shifts and circulatory changes. In chronic renal failure (CRF) Na+/K+ATP-ase is depressed, whereas endogenous digoxin-like factor (EDLF) is elevated. Our aim was to characterize HD-induced cardiovascular adaptation and its possible links to Na+/K+ATP-ase and EDLF. Eleven children with CRF on HD (aged 14.7 +/- 3.7 years) and 11 healthy children were investigated for basic circulatory parameters. Thoracic impedance (Zo) and circulatory parameters were monitored by impedance cardiography (ICG) during HD. Erythrocyte Na+/K+ATP-ase and EDLF were measured before and after HD. Up to the loss of 6% of total body weight, Zo rose linearly with fluid removal, above this no further increase occurred. Heart rate and mean arterial pressure (MAP) were inversely related (r = -0.97); MAP rose in the first and decreased in the second part of HD. Systemic vascular resistance paralleled MAP, whereas stroke volume rapidly decreased, but stabilized in the second part of HD. The ratio of preejection period/ventricular ejection time (PEP/VET) correlated positively with HD duration (r = 0.92), suggesting diminished cardiac filling. Cardiac index (CI) remained stable. EDLF was high in uremia accompanied by depressed Na+/K+ATP-ase (P < 0.05 and P < 0.01, respectively). Following HD Na+/K+ATP-ase normalized. Correlation between Na+/K+ATP-ase activity and MAP was linear (r = 0.85). In conclusion, ICG during HD provides detailed information concerning circulatory adaptation resulting in stable CI, suggesting that the dialysis-induced hypovolemia is compensated by the centralization of the blood volume. Changes of Na+/K+ATP-ase indicate that dialyzable blood pressure-regulating substance(s) inhibit(s) the pump. However, lack of further correlation between Na+/K+ATP-ase, EDLF, and cardiovascular parameters indicates the complexity of the regulatory processes.
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Digoxina , Corazón/fisiopatología , Diálisis Renal , Adolescente , Presión Sanguínea , Cardenólidos , Cardiografía de Impedancia , Niño , Femenino , Humanos , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/terapia , Masculino , Saponinas/sangre , ATPasa Intercambiadora de Sodio-Potasio/sangre , Resistencia VascularRESUMEN
To evaluate the presence of autonomic neuropathy in childhood uremia, cardiovascular autonomic reflexes were examined in children with chronic renal failure. Cardiovascular autonomic reflexes of 10 uremic patients on chronic dialysis and 10 transplanted patients were compared to assess the effect of transplantation on autonomic neuropathy. Resting heart rate, heart rate changes induced by deep breathing, by Valsalva maneuver, and following standing up, and blood pressure change induced by handgrip test were examined. Of the 10 uremic children, 4 showed early involvement and 2 had definite involvement of autonomic neuropathy. Only 1 of the 10 transplanted patients showed early signs of autonomic neuropathy. Autonomic tests demonstrated predominantly parasympathetic dysfunction. In conclusion, cardiovascular autonomic neuropathy is not rare in children and adolescents and young adults with chronic renal failure. In contrast, the prevalence is very low in transplanted patients with similar uremic precedents. Efforts should be made to prevent or delay this uremia-related complication.
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Enfermedades del Sistema Nervioso Autónomo/etiología , Uremia/complicaciones , Adolescente , Presión Sanguínea , Ejercicios Respiratorios , Niño , Mareo , Fuerza de la Mano , Sistema de Conducción Cardíaco/fisiopatología , Frecuencia Cardíaca , Humanos , Trasplante de Riñón , Sistema Nervioso Parasimpático/fisiopatología , Diálisis Peritoneal Ambulatoria Continua , Diálisis Renal , Uremia/fisiopatología , Uremia/terapia , Maniobra de ValsalvaRESUMEN
AIM: To study bone turnover following renal transplantation using a panel of biochemical markers and to correlate the results with both areal and volumetric bone mineral density (BMD). PATIENTS: A total of 31 patients aged 18.1 years were transplanted 5.4 years before this study. Control patients (n = 31) were age and gender matched. METHODS: In addition to measurement of biochemical markers, BMD was measured by single photon absorptiometry and peripheral quantitative computed tomography on the non-dominant radius. RESULTS: Patients had reduced glomerular filtration rate, raised concentrations of serum phosphate, serum procollagene type I carboxy terminal propeptide, osteocalcin, and serum procollagene type I cross linked carboxy terminal telopeptide. The differences were still significant if only patients with normal intact parathyroid hormone were considered. BMD single photon absorptiometry Z score for age was significantly decreased. Following standardisation for height the differences were no longer present. With volumetric techniques patients had normal trabecular but decreased cortical and total BMD compared to age matched controls, but there was no difference from height matched controls. CONCLUSION: Markers of bone turnover are increased following renal transplantation. However, the biochemical analysis did not allow conclusions to be drawn on the bone mineral content. BMD single photon absorptiometry Z score corrected for height and BMD measured by quantitative computed tomography compared to height matched controls were normal in paediatric renal transplantation patients. Height matched controls should be used in both areal and volumetric BMD measurements in states of growth failure.
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Densidad Ósea/fisiología , Remodelación Ósea/fisiología , Trasplante de Riñón , Absorciometría de Fotón , Adolescente , Adulto , Biomarcadores/análisis , Estatura , Estudios de Casos y Controles , Niño , Estudios Transversales , Femenino , Tasa de Filtración Glomerular/fisiología , Humanos , Masculino , Osteocalcina/sangre , Fragmentos de Péptidos/sangre , Fosfatos/sangre , Procolágeno/sangre , Tomografía Computarizada por Rayos XRESUMEN
The mechanisms of sodium retention in edema-forming minimal change nephrotic syndrome (MCNS) have not been completely evaluated. The aim of this study was to characterize the transmembrane sodium transport in nephrotic syndrome by measuring the erythrocyte sodium-lithium countertransport (SLC) in vitro. Eighteen children with MCNS were studied in the edema-forming state, and subsequently at the beginning of remission. Nephrotic children with edema retained sodium (10+/-12 micromol/day) and had a higher SLC [426+/-118 vs. 281+/-60 micromol/l red blood cells (RBC) per hour, P=0.003). The intracellular sodium concentration of nephrotics was 6.1+/-2.1 mmol/l RBC, which did not differ from that of controls (6.42+/-2.24, n=13). In remission sodium balance became negative (-30+/-21 mmol/day), and the SLC decreased but still differed significantly from control values (P=0.009). The intracellular sodium content decreased to 4.4+/-0.9 mmol/l RBC (P=0.002). There was a negative correlation between erythrocyte SLC and plasma albumin concentration (r=0.48, P=0.003), and urinary sodium excretion rate (r=0.66, P=0.001). In conclusion, erythrocyte SLC is high in the edema-forming state of childhood nephrotic syndrome and decreases with the onset of remission. A role for the SLC in the altered sodium homeostasis of nephrotic syndrome is suggested.
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Antiportadores/sangre , Síndrome Nefrótico/sangre , Niño , Preescolar , Edema/etiología , Eritrocitos/metabolismo , Femenino , Humanos , Masculino , Natriuresis/fisiología , Síndrome Nefrótico/complicaciones , Síndrome Nefrótico/fisiopatología , Valores de Referencia , Sodio/sangreRESUMEN
Recently, a new human virus hepatitis G virus was identified. The aim of the present study was to use a combination of the reverse transcription-polymerase chain reaction and a new test for antibodies to the viral envelope protein E2 to assess the prevalence of hepatitis G virus infection in sera of children and adults treated with hemodialysis or peritoneal dialysis as well as in sera of those who underwent renal transplantation. Hepatitis G virus RNA prevalence was higher in the shole group of patients with renal failure than in control group. The difference between hepatitis RNA prevalence in transplanted group and in control group was found to be significant. Anti-E2, which are is considered as an indicator of a past hepatitis G virus infection, were detected in the similar rate in the treated and control subjects. Time on hemodialysis was significantly longer in hepatitis G virus infected patients as compared to uninfected patients and all patients with hepatitis G virus RNA have a history of blood transfusions. Patients with renal failure treated with dialysis or subjected to renal transplantation are at increased risk of acquiring the hepatitis G virus infection. Higher rates of the hepatitis G virus RNA and similar prevalence of anti-E2 in patients with renal failure as compared to controls suggest that the rate of hepatitis G virus infection resolution in immunosuppressed patients with renal failure might be lower than in immunocompetent subjects.
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Flaviviridae/aislamiento & purificación , Trasplante de Riñón , Diálisis Peritoneal Ambulatoria Continua , Diálisis Renal , Adolescente , Adulto , Niño , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/virologíaRESUMEN
The urinary enzymes Gamma Glutamyl Transferase (GGT), Alkaline Phosphatase (ALP), Leucine-Arylamidase (LAS), and Dipeptidyl-Peptidase-IV (DPP-IV) were measured before and after endoscopic treatment of vesico-ureteric reflux (VUR) in two groups of twenty children. Ten patients had undergone successful endoscopic corrective surgery for VUR, another 10 patients had unsuccessful endoscopic intervention. After successful treatment the activity of LAS in the urine did not change, but GGT, ALP and DPP-IV activity in the urine was 2-5 times higher than before treatment (P < 0.03 for all three enzymes). Considerable changes of urinary enzyme activity were not observed following unsuccessful endoscopic treatment. Our data and the literature are contradictory. However, this contradiction might be explained by the differences in urine sampling methods. Our patients received the same chemoprophylactic drug at the time of both urine samplings, a point not considered by other researchers. The extent of increase of enzyme activity after endoscopic treatment of VUR did not reach the level that would permit the use of investigated enzymes for screening, because the observed changes did not exceed the limits of the normal range.
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Escleroterapia/métodos , Reflujo Vesicoureteral/enzimología , Reflujo Vesicoureteral/terapia , Fosfatasa Alcalina/orina , Estudios de Casos y Controles , Niño , Dipeptidil Peptidasa 4/orina , Femenino , Humanos , Leucil Aminopeptidasa/orina , Masculino , Soluciones Esclerosantes/uso terapéutico , gamma-Glutamiltransferasa/orinaRESUMEN
The recombinant human growth hormone (rhGH), currently used in supraphysiological doses to promote growth acceleration in chronic renal failure children (CRF), also has the ability to influence their impaired immune functions. The effect of human growth hormone on the lymphoproliferative response in vitro was analyzed in the peripheral blood lymphocytes of 25 healthy and 11 uremic children. In 72% of the uremic cases and in 60% of the healthy individual children the hormone increased the lymphoproliferation alone, and/or when used in combination with phytohaemagglutinine. The range of the effective hormone concentrations differed individually. Using semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) a great variation in the gene expression of growth hormone- (GH)-receptor in peripheral lymphocytes was detected. The respiratory burst activity of peripheral polymorphonuclear leukocytes (PMN) in vitro, in response to GH alone and when combined with suboptimal dose of phorbolester (PMA), was assessed by measuring luminol enhanced chemiluminescence in ten uremic and 18 healthy children. In six out of the ten of the CRF patients and in eight out of 18 of the healthy children the GH enhanced the oxidative burst activity of granulocytes provoked by a suboptimal dose of PMA. However, the effective doses (10, 50 and 300 ng/ml) and incubation times (0, 45 and 90 min) showed individual variations. Our data suggest that rhGH treatment in uremic children could be advantageous considering this population's enhanced susceptibility to bacterial, viral and fungal infections.
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Granulocitos/efectos de los fármacos , Hormona de Crecimiento Humana/farmacología , Fallo Renal Crónico/metabolismo , Linfocitos/efectos de los fármacos , Adolescente , Niño , Ensayo de Inmunoadsorción Enzimática , Femenino , Regulación del Desarrollo de la Expresión Génica/genética , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Sistema Inmunológico/efectos de los fármacos , Sistema Inmunológico/fisiopatología , Fallo Renal Crónico/tratamiento farmacológico , Fallo Renal Crónico/fisiopatología , Masculino , Neopterin/sangre , Neutrófilos/efectos de los fármacos , Reacción en Cadena de la Polimerasa , Receptores de Somatotropina/genética , Estallido Respiratorio/efectos de los fármacos , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
The urinary enzymes Gamma Glutamyl Transferase (GGT), Alkaline Phosphatase (ALP), Leucine-Arylamidase (LAS) and Dipeptidyl-Peptidase-IV (DPP-IV) were measured before and after endoscopic treatment of vesico-ureteric reflux (VUR) in two groups of twenty children's. Ten patients had undergone successful endoscopic corrective surgery for VUR, another 10 patients had unsuccessful endoscopic intervention. After successful treatment the activity of LAS in the urine did not change, but that of GGT, ALP and DDP-IV activity in the urine was 2-5 times higher than before treatment (P < 0.03 for all three enzymes). Considerable changes of urinary enzymes' activity were not observed following unsuccessful endoscopic treatment. Our data and the literature are contradictory. However this contradiction might be explained by the differences in urine sampling methods. Our patients received the same chemoprofilactic drug at the time of both urine sampling, a point not considered by other researchers. The extent of increase of enzyme activity after endoscopic treatment of VUR did not reach the level that would permit the use of investigated enzymes for screening, because the observed changes did not exceed the limits of the normal range.
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Reflujo Vesicoureteral/cirugía , Adolescente , Fosfatasa Alcalina/orina , Niño , Preescolar , Endoscopía , Humanos , Leucil Aminopeptidasa/orina , Peptidil-Dipeptidasa A/orina , Silicio/uso terapéutico , Reflujo Vesicoureteral/enzimología , gamma-Glutamiltransferasa/orinaRESUMEN
Nephrogenic diabetes insipidus is a rare, mostly X-linked recessive disorder characterised by renal tubular resistance to the antidiuretic effect of arginine vasopressin. The gene responsible for the X-linked nephrogenic diabetes insipidus, the G-protein-coupled vasopressin V2-receptor, has been localised on the Xq28 region. In this study four patients were investigated with molecular genetic methods. Diagnosis was based on clinical symptoms and lack of increase of urinary osmolality after administration of the arginine vasopressin, or the synthetic vasopressin analogue DDAVP. Three different mutations (C112R, N317K, W323S) were found in three patients, while no mutation was detected in the fourth patient. Since earlier histiocytosis X has been diagnosed in this patient, this patient has probably central diabetes insipidus. Although the main symptoms of the disease can be found in all patients, there are significant differences in the seriousness of the symptoms as well as in some other symptoms. The explanations might be the different mutations in the V2-receptor gene and the various other genetic and environmental factors; these findings provide further evidence that X-linked nephrogen diabetes insipidus results from defects in the V2-receptor gene.
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Diabetes Insípida Nefrogénica/genética , Receptores de Vasopresinas/genética , Humanos , Biología Molecular , MutaciónRESUMEN
The aim of the present study was to use a combination of the reverse transcription-polymerase chain reaction and a new diagnostic test for antibodies against the viral envelope protein E2 to assess the prevalence of hepatitis G virus (GBV-C/HGV) infection in sera of Hungarian children on hemodialysis (HD) or peritoneal dialysis (CAPD), as well as in sera of renal transplant patients (RTx). The GBV-C/HGV RNA prevalence was significantly higher in the whole group of children with renal failure (18.5%) than in the control group (children with urinary tract infection, 2.5%). The difference between the GBV-C/HGV RNA prevalence in the RTx group (33.3%) and in the control group (2.5%) was significant (P = 0.007). Anti-E2, which is considered an indicator of a past GBV-C/ HGV infection, was detected in 10% (1/10) of HD patients, in 33.3% (4/12) of RTx patients, but in none of the children on CAPD. These differences were not significant. Children receiving a renal graft are at an increased risk of developing GBV-C/HGV infection, which may be attributed to the immunosuppressive drugs necessary to maintain the grafts.
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Flaviviridae , Hepatitis Viral Humana/epidemiología , Trasplante de Riñón , Diálisis Peritoneal Ambulatoria Continua , Adolescente , Adulto , Anticuerpos Antivirales , Niño , Ensayo de Inmunoadsorción Enzimática , Femenino , Flaviviridae/inmunología , Hepatitis Viral Humana/complicaciones , Hepatitis Viral Humana/virología , Humanos , Hungría/epidemiología , Masculino , Reacción en Cadena de la PolimerasaRESUMEN
Erythrocyte sodium-potassium (Na+/K+)-ATPase and sodium-lithium (Na+/Li+) countertransport activities were measured in 18 children (aged 9.6 years, range 6-16 years) with idiopathic hypercalciuria (IHU) to evaluate cellular Na handling. The effect of chronic thiazide administration on these parameters and on bone mineral density was also evaluated. Patients with IHU had significantly lower erythrocyte Na+/K+-ATPase activity than 23 age-matched healthy controls (mean +/- SEM 2,156 +/- 110 micromol P/l erythrocyte per hour vs. 3,165 +/- 175, P < 0.01). Thiazide treatment significantly lowered urinary calcium excretion; this was followed by a slight suppression of intact parathyroid hormone (iPTH). The urinary calcium/creatinine ratio before and during treatment was 0.90 +/- 0.07 mmol/mmol versus 0.51 +/- 0.06 respectively, P < 0.01. The corresponding iPTH levels were 5.9 +/- 0.6 pmol/l and 5.1 +/- 0.7, P < 0.05. The Na+/K+-ATPase activity increased significantly (2,769 +/- 169 micromol P/l erythrocyte per hour vs. 2,156 +/- 110 in the control period, P < 0.01) and the Na+/Li+ countertransport decreased (268 +/- 28 micromol Li/l erythrocyte per hour vs. 328+26 in the control period, P < 0.03). The bone mineral density Z score rose from -1.3 +/- 0.26 to -0.8 +/- 0.22 (P < 0.03). We conclude that IHU is accompanied by abnormalities of erythrocyte Na+/K+-ATPase and Na+/Li+ countertransport which are corrected by chronic hydrochlorothiazide administration. These changes could model alterations in renal tubular transport mechanisms still to be elucidated. Chronic thiazide treatment also has a positive effect on bone mineral density.
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Densidad Ósea/fisiología , Calcio/orina , Hidroclorotiazida/efectos adversos , Inhibidores de los Simportadores del Cloruro de Sodio/efectos adversos , Sodio/metabolismo , Adolescente , Niño , Diuréticos , Eritrocitos/enzimología , Eritrocitos/metabolismo , Femenino , Humanos , Masculino , Hormona Paratiroidea/sangre , Potasio/sangre , Sodio/sangre , ATPasa Intercambiadora de Sodio-Potasio/sangreRESUMEN
Recent studies have demonstrated inconsistencies in the use of certain images for classifying proximal humerus fractures. Our purpose was to determine whether three-dimensional computed tomography or the level of expertise of the observers would improve the reliability and reproducibility of identifying specific anatomic fragments in proximal humerus fractures. Two groups of observers, nonexperts and experts in shoulder surgery, were asked to review the radiographs and three-dimensional computed tomography scans of 12 patients with proximal humerus fractures. Observers were asked to identify displaced fracture fragments, dislocation, and articular surface fractures. Both groups of observers displayed suboptimal reliability for the identification of displaced fracture fragments. The addition of three-dimensional computed tomography scans did not improve the reliability or reproducibility. Poor agreement for the purpose of classification seems to occur at the most fundamental level, the pathoanatomic description of the fracture. Inconsistencies may have been due to imprecise identification and measurement of individual fracture fragments, differing interpretations of the pathoanatomy, or both.
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Fracturas del Húmero/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Humanos , Fracturas del Húmero/patología , Variaciones Dependientes del Observador , Reproducibilidad de los ResultadosRESUMEN
There is debate among orthopaedists about the efficacy of steroid therapy to treat painful joints. Using an uncontrolled, retrospective study, we examined the usefulness of local corticosteroid injections in thirty-one patients (twenty-four men, seven women) with isolated AC joint arthropathy. No patients had signs of impingement or rotator cuff disease. All injections were performed using a standardized technique with each patient receiving 1cc Celestone/Soluspan or Dexamethasone and 2cc Lidocaine. At an average follow-up of nineteen months, patients were asked to answer questions regarding activity of daily living, according to the American Shoulder and Elbow Surgeons (ASES) format, average level of pain, length of pain relief from steroid injection, and time to return to full activity. Four patients could not be contacted for follow-up questions and, therefore, were excluded from the study leaving twenty-seven patients. Pain and function improved in twenty-five of twenty-seven (93%) patients after injection. Mean duration of improvement was twenty days (range, two hours to three months). Two patients reported continued relief at 1.5 and two years after injection. Due to persistent, insidious pain, eighteen of twenty-seven (67%) patients underwent distal clavicle excision an average of four months after injection. Overall, twenty-two of twenty-seven (81%) patients failed to obtain long-term relief from the injection. The results of this study suggest that the administration of local corticosteroids into the AC joint may provide short-term pain relief, but does not alter the natural progression of disease.
Asunto(s)
Articulación Acromioclavicular , Antiinflamatorios/administración & dosificación , Glucocorticoides/administración & dosificación , Adulto , Anciano , Betametasona/administración & dosificación , Dexametasona/administración & dosificación , Femenino , Humanos , Inyecciones Intraarticulares , Masculino , Persona de Mediana Edad , Osteoartritis/tratamiento farmacológico , Dimensión del Dolor , Estudios RetrospectivosRESUMEN
The enzyme Na+/K(+)-ATPase plays a central role in the regulation of transmembrane ionic transports. According to previous reports its activity decreased in uremic state. The activity of Na+/K(+)-ATPase in detergent pretreated erythrocytes was studied in seven uremic children prior to and following the hemodialysis (HD) session. Additionally, the level of endogenous digoxin like factors in the plasma (EDLF) was determined. Before the HD session the Na+/K(+)-ATPase activity decreased compared to the control value (mean +/- SD: 2078 +/- 527 vs 3245 +/- 362 nmol P/ml RBC/h, p < 0.01). Following HD it became normal (3366 +/- 952 nmol P/ml RBC/h, n.s.). Prior to the HD the EDLF level was higher, while after the HD no difference was noted from the control value (0.29 +/- 0.04, p < 0.05; 0.24 +/- 0.04 n. s. vs control; 0.21 +/- 0.04 ng/ml). Before the HD blood pressure was significantly elevated compared to the control (117 +/- 20/92 +/- 18 vs 95 +/- 2/64 +/- 2 Hgmm, p < 0.05). By the end of the HD it became normal (100 +/- 14/79 +/- 11, n.s.). Although no correlation was found between the EDLF level and Na+/K(+)-ATPase activity, a positive significant correlation was found between the changes of enzyme activity and the changes in the systolic (r = 0.83, p < 0.05) and diastolic (r = 0.82, p < 0.05) blood pressure during the HD. Our results indicate, that in uremic children the Na+/K+ pump is inhibited by a dialysable, blood-pressure regulator substance and so the enzyme activity elevates following the HD session. However, decreased blood pressure activates counterregulatory mechanisms, which-to lower extent-inhibit the activity of the pump.
Asunto(s)
Adenosina Trifosfatasas/sangre , Digoxina , Inhibidores Enzimáticos/sangre , Eritrocitos/química , Potasio/sangre , Diálisis Renal , Saponinas/sangre , Sodio/sangre , Uremia/sangre , Adolescente , Presión Sanguínea , Cardenólidos , Niño , Femenino , Humanos , Masculino , Uremia/enzimologíaRESUMEN
The Na(+)-K+ ATPase enzyme plays an essential role in the regulation of cell composition and volume. Enzyme activity itself is regulated by substrate availability and several hormones. In adult uraemic patients red blood cell Na(+)-K+ ATPase activity is decreased. However, it is unknown if children with uraemia exhibit the same phenomenon. Therefore, in the present study we examined whether endogenous digoxin-like factors (EDLF) and physicochemical membrane properties play a role in the regulation of erythrocyte Na(+)-K+ ATPase activity in uraemic children and adolescents. Healthy age-matched children were used as controls. Enzyme activity was measured in detergent-pretreated red blood cells and erythrocyte ghosts. Na(+)-K+ ATPase activity (2204 +/- 538 nmol Pi ml erythrocyte-1 h-1 in detergent pretreated erythrocytes; 204 +/- 56 nmol Pi mg protein-1 h-1 in ghosts) in adolescents with uraemia was lower compared to controls (3245 +/- 362 nmol Pi ml erythrocyte-1 h-1; 266 +/- 37 nmol Pi mg protein-1 h-1, p < 0.001, p < 0.05, respectively). Plasma levels of EDLF were elevated in uraemic patients (0.30 +/- 0.05 versus 0.21 +/- 0.04 ng ml-1, p < 0.01). Furthermore, the membrane lipid component was decreased in patients with uraemia, while the cholesterol/phospholipid ratio and membrane fluidity were similar in both groups. No correlation was found between the decrease in Na(+)-K+ ATPase and the increase in EDLF concentration and altered membrane lipid components. Our results demonstrate, that similar to the findings of adults, the activity of Na(+)-K+ ATPase is diminished in uraemic adolescent patients, and that uraemia-associated elevation in EDLF and altered membrane components do not play a role in the down-regulation of Na(+)-K+ ATPase. Therefore other factors (presence of other inhibitors and/or reduced number of enzyme molecules) should contribute to the lower activity of the Na(+)-K+ pump.