RESUMO
Immune thrombotic thrombocytopenic purpura (iTTP) is an ultra-rare, life-threatening disorder, mediated through severe ADAMTS13 deficiency causing multi-system micro-thrombi formation, and has specific human leukocyte antigen associations. We undertook a large genome-wide association study to investigate additional genetically distinct associations in iTTP. We compared two iTTP patient cohorts with controls, following standardized genome-wide quality control procedures for single-nucleotide polymorphisms and imputed HLA types. Associations were functionally investigated using expression quantitative trait loci (eQTL), and motif binding prediction software. Independent associations consistent with previous findings in iTTP were detected at the HLA locus and in addition a novel association was detected on chromosome 3 (rs9884090, P=5.22x10-10, odds ratio 0.40) in the UK discovery cohort. Meta-analysis, including the French replication cohort, strengthened the associations. The haploblock containing rs9884090 is associated with reduced protein O-glycosyltransferase 1 (POGLUT1) expression (eQTL P<0.05), and functional annotation suggested a potential causative variant (rs71767581). This work implicates POGLUT1 in iTTP pathophysiology and suggests altered post-translational modification of its targets may influence disease susceptibility.
Assuntos
Púrpura Trombocitopênica Idiopática , Púrpura Trombocitopênica Trombótica , Proteína ADAMTS13/genética , Loci Gênicos , Estudo de Associação Genômica Ampla , Glucosiltransferases/genética , Humanos , Púrpura Trombocitopênica Idiopática/genética , Púrpura Trombocitopênica Trombótica/genéticaRESUMO
Background/aim: Children on dialysis are under increased risk of influenza and invasive pneumococcal disease. Although vaccination against these microorganisms are recommended in dialysis patients and despite the fact that these vaccines can reduce disease burden and rates of hospitalization due to infection, vaccination rates are below expected and desired. We aimed to evaluate influenza and pneumococcal vaccination and infection rates in European pediatric dialysis centers. Materials and methods: In 16 centers from 11 countries, 357 pediatric dialysis patients were evaluated retrospectively during 1 year of observation period between 01.01.2014 and 01.01.2015. Results: In all centers, vaccination policy included immunization of dialysis patients with inactive influenza vaccine and pneumococcal conjugate vaccine (PCV). Fifty percent of the centers recommended pneumococcal polysaccharide vaccine following routine PCV series. A significantly higher pneumococcal vaccination rate (43.9%) was seen in peritoneal dialysis (PD) patients compared to those on hemodialysis (HD) (32.9%) (p = 0.035), while the rates for influenza were similar (42.4% and 46.1% respectively, p = 0.496). Among all dialysis patients, 2.2% (n = 8) developed pneumonia and 6.4% (n = 23) was infected by Influenza. Pneumococcic pneumonia rate was 5% for 140 patients who received antipneumococcal vaccine, while only one pneumonia episode was recorded out of 217 unvaccinated patients (p = 0.007). The influenza virus infection rates were similar for patients vaccinated and nonvaccinated (7 % and 6 %, respectively). Conclusions: Although influenza and pneumococcal vaccines are highly recommended in pediatric dialysis patients, vaccination rates were lower than expected. Pneumococcal vaccination rates were higher in PD compared to the patients on HD. The rate of children with influenza infection was higher than pneumonia. The efficacy of influenza and pneumococcal vaccines was highlighted by the low infection rates. Higher pneumonia rates in patients vaccinated against pneumococcus compared to unvaccinated ones might be due to coexisting risk factors.
Assuntos
Imunização/estatística & dados numéricos , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Nefrologia , Vacinas Pneumocócicas/administração & dosagem , Vacinação/estatística & dados numéricos , Adolescente , Anticorpos/análise , Criança , Pré-Escolar , Humanos , Lactente , Nefrologia/normas , Pediatria , Diálise Renal/métodos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Estudos Retrospectivos , Sociedades Médicas , Streptococcus pneumoniaeRESUMO
BACKGROUND: Steroid-sensitive nephrotic syndrome (SSNS), the most common form of nephrotic syndrome in childhood, is considered an autoimmune disease with an established classic HLA association. However, the precise etiology of the disease is unclear. In other autoimmune diseases, the identification of loci outside the classic HLA region by genome-wide association studies (GWAS) has provided critical insights into disease pathogenesis. Previously conducted GWAS of SSNS have not identified non-HLA loci achieving genome-wide significance. METHODS: In an attempt to identify additional loci associated with SSNS, we conducted a GWAS of a large cohort of European ancestry comprising 422 ethnically homogeneous pediatric patients and 5642 ethnically matched controls. RESULTS: The GWAS found three loci that achieved genome-wide significance, which explain approximately 14% of the genetic risk for SSNS. It confirmed the previously reported association with the HLA-DR/DQ region (lead single-nucleotide polymorphism [SNP] rs9273542, P=1.59×10-43; odds ratio [OR], 3.39; 95% confidence interval [95% CI], 2.86 to 4.03) and identified two additional loci outside the HLA region on chromosomes 4q13.3 and 6q22.1. The latter contains the calcium homeostasis modulator family member 6 gene CALHM6 (previously called FAM26F). CALHM6 is implicated in immune response modulation; the lead SNP (rs2637678, P=1.27×10-17; OR, 0.51; 95% CI, 0.44 to 0.60) exhibits strong expression quantitative trait loci effects, the risk allele being associated with lower lymphocytic expression of CALHM6. CONCLUSIONS: Because CALHM6 is implicated in regulating the immune response to infection, this may provide an explanation for the typical triggering of SSNS onset by infections. Our results suggest that a genetically conferred risk of immune dysregulation may be a key component in the pathogenesis of SSNS.
Assuntos
Canais de Cálcio/genética , Glicoproteínas de Membrana/genética , Síndrome Nefrótica/genética , Esteroides/uso terapêutico , Alelos , Proteína de Ligação a Androgênios/genética , Criança , Bases de Dados Factuais , Epitopos/química , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Humanos , Sistema Imunitário , Masculino , Síndrome Nefrótica/tratamento farmacológico , Razão de Chances , Peptídeos/química , Polimorfismo de Nucleotídeo Único , Locos de Características QuantitativasRESUMO
BACKGROUND: Management of children with congenital nephrotic syndrome (CNS) is challenging. Bilateral nephrectomies followed by dialysis and transplantation are practiced in most centres, but conservative treatment may also be effective. METHODS: We conducted a 6-year review across members of the European Society for Paediatric Nephrology Dialysis Working Group to compare management strategies and their outcomes in children with CNS. RESULTS: Eighty children (50% male) across 17 tertiary nephrology units in Europe were included (mutations in NPHS1, n = 55; NPHS2, n = 1; WT1, n = 9; others, n = 15). Excluding patients with mutations in WT1, antiproteinuric treatment was given in 42 (59%) with an increase in S-albumin in 70% by median 6 (interquartile range: 3-8) g/L (P < 0.001). Following unilateral nephrectomy, S-albumin increased by 4 (1-8) g/L (P = 0.03) with a reduction in albumin infusion dose by 5 (2-9) g/kg/week (P = 0.02). Median age at bilateral nephrectomies (n = 29) was 9 (7-16) months. Outcomes were compared between two groups of NPHS1 patients: those who underwent bilateral nephrectomies (n = 25) versus those on conservative management (n = 17). The number of septic or thrombotic episodes and growth were comparable between the groups. The response to antiproteinuric treatment, as well as renal and patient survival, was independent of NPHS1 mutation type. At final follow-up (median age 34 months) 20 (80%) children in the nephrectomy group were transplanted and 1 died. In the conservative group, 9 (53%) remained without dialysis, 4 (24%; P < 0.001) were transplanted and 2 died. CONCLUSION: An individualized, stepwise approach with prolonged conservative management may be a reasonable alternative to early bilateral nephrectomies and dialysis in children with CNS and NPHS1 mutations. Further prospective studies are needed to define indications for unilateral nephrectomy.
Assuntos
Nefrectomia , Síndrome Nefrótica/cirurgia , Síndrome Nefrótica/terapia , Albuminas/uso terapêutico , Criança , Pré-Escolar , Europa (Continente) , Feminino , Humanos , Lactente , Masculino , Proteínas de Membrana/genética , Mutação , Nefrologia/métodos , Síndrome Nefrótica/genética , Pediatria/métodos , Estudos Prospectivos , Proteinúria/terapia , Estudos Retrospectivos , Sepse/complicações , Trombose/complicaçõesRESUMO
BACKGROUND: Children with congenital nephrotic syndrome (CNS) commonly develop end stage renal failure in infancy and require dialysis, but little is known about the complications and outcomes of dialysis in these children. METHODS: We conducted a retrospective case note review across members of the European Society for Pediatric Nephrology Dialysis Working Group to evaluate dialysis management, complications of dialysis, and outcomes in children with CNS. RESULTS: Eighty children (50% male) with CNS were identified form 17 centers over a 6-year period. Chronic dialysis was started in 44 (55%) children at a median age of 8 (interquartile range 4-14) months. Of these, 17 (39%) were on dialysis by the age of 6 months, 30 (68%) by 1 year, and 40 (91%) by 2 years. Peritoneal dialysis (PD) was the modality of choice in 93%, but 34% switched to hemodialysis (HD), largely due to catheter malfunction (n = 5) or peritonitis (n = 4). The peritonitis rate was 0.77 per patient-year. Weight and height SDS remained static after 6 months on dialysis. In the overall cohort, at final follow-up, 29 children were transplanted, 18 were still on dialysis (15 PD, 3 HD), 19 were in pre-dialysis chronic kidney disease (CKD), and there were 14 deaths (8 on dialysis). Median time on chronic dialysis until transplantation was 9 (6-18) months, and the median age at transplantation was 22 (14-28) months. CONCLUSIONS: Infants with CNS on dialysis have a comparable mortality, peritonitis rate, growth, and time to transplantation as infants with other primary renal diseases reported in international registry data.
Assuntos
Falência Renal Crônica/terapia , Transplante de Rim , Síndrome Nefrótica/terapia , Diálise Renal , Insuficiência Renal Crônica/terapia , Fatores Etários , Pré-Escolar , Progressão da Doença , Europa (Continente) , Feminino , Humanos , Lactente , Recém-Nascido , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etiologia , Falência Renal Crônica/mortalidade , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Masculino , Síndrome Nefrótica/congênito , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/mortalidade , Diálise Peritoneal , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/mortalidade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Increased plasma cell infiltration in renal allograft biopsies is a rare finding associated with poor outcome in adult renal transplant recipients. The clinical impact of increased plasma cell infiltrates in paediatric renal transplant recipients (pRTR) remains unknown. METHODS: We conducted a retrospective case-control study from April 1996 to March 2014 comparing the outcome of pRTR with increased (>10 % of infiltrate) plasma cells in renal transplant biopsies to a control cohort of pRTR without increased plasma cell infiltration but similar grade of rejection according to Banff classification. RESULTS: Increased plasma cell infiltrates were present in 14 of 162 (9 %) reviewed pRTR aged 3.2-17.5 (median 13.4) years at time of transplantation. Compared with 14 pRTR renal transplant biopsies without significantly increased plasma cells, there were no significant differences in mismatch and baseline estimated glomerular filtration rate (eGFR). Plasma cells were present in case biopsies at a maximal density of 14-116 (median 33) plasma cells/HPF. Increased plasma cells were associated with decreased eGFR at biopsy (22 vs. 49 ml/min/1.73 m2; p < 0.001) and 4 weeks post-biopsy (26 vs. 56 ml/min/1.73 m2; p < 0.001) despite comparable eGFR 4 weeks prior to biopsy. Increased plasma cells were further associated with significantly increased frequency of renal allograft loss (71 % vs. 7 %; p < 0.001) at 0-27 (median 2) months after biopsy. CONCLUSION: Increased plasma cell infiltrates in pRTR are uncommon but associated with significantly reduced renal allograft survival as well as significantly reduced allograft function in surviving grafts.
Assuntos
Rejeição de Enxerto/patologia , Transplante de Rim , Plasmócitos/patologia , Adolescente , Biópsia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/epidemiologia , Humanos , Terapia de Imunossupressão , Estimativa de Kaplan-Meier , Masculino , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento , Resultado do TratamentoRESUMO
BACKGROUND: Whilst still rare, the incidence of paediatric stone disease is increasing in developed countries and it is important to evaluate the aetiology. We set up a dedicated renal stone service for children combining medical and surgical expertise in 1993 and now have a large case series of children to investigate the epidemiology. METHODS: A retrospective hospital note review of children presenting with kidney stones during the last 22 years (1993-2015) was conducted. All patients had a comprehensive infective and metabolic screen and were classified as metabolic, infective or idiopathic stone disease. RESULTS: Five hundred eleven patients (322 male) were reviewed. The median age of presentation was 4.4y for males (1 m-16.6y) and 7.3y (1-18.5y) for females with a median height and weight on the 25th centile for male and on 10th and 25th for female, respectively. One hundred seventy five (34%) had an underlying metabolic abnormality, 112 (22%) had infective stones and 224 (44%) were classified as idiopathic. Of the 175 patients with a metabolic abnormality: 91 (52%) had hypercalciuria (76 persistent and 15 transient), 37 (21%) hyperoxaluria, 38 (22%) cystinuria, 3 (2%) abnormalities in the purine metabolism and the remainder other metabolic abnormalities. Bilateral stones occurred in 27% of the metabolic group compared to 16% in the non-metabolic group (OR 0.2, p < 0.05). Urinary tract infection was a common complication (27%) in the metabolic group. CONCLUSIONS: In this paper, we present the largest cohort of paediatric stone disease reported from a developed country giving details on both, clinical and laboratory data. We show that in the majority of the patients there is an identifiable underlying metabolic and/or infective aetiology emphasizing the importance of a full work up to provide adequate treatment and prevent recurrence. Moreover, we show that stone disease in children, in contrast to the adult population, does not seem to be associated with obesity, as children have a weight below average at presentation.
Assuntos
Cálculos Renais/diagnóstico , Cálculos Renais/epidemiologia , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/epidemiologia , Infecções Urinárias/diagnóstico , Infecções Urinárias/epidemiologia , Adolescente , Distribuição por Idade , Causalidade , Criança , Pré-Escolar , Comorbidade , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Prevalência , Fatores de Risco , Distribuição por SexoRESUMO
BACKGROUND: Steroid-sensitive nephrotic syndrome is the most common form of nephrotic syndrome in childhood, defined by the response to treatment with glucocorticoids with consequent remission. While most children eventually experience spontaneous resolution of the disease, some have a difficult course with frequent relapses or steroid dependence nephrotic syndrome (FRSDNS). The consequent steroid toxicity often prompts administration of other immunosuppressive drugs, traditionally cyclophosphamide. Recently, rituximab has been reported as effective in this disorder, but long-term experience is lacking. METHODS: Retrospective note review of all children with FRSDNS treated with a first course of cyclophosphamide and/or rituximab in our center between December 2006 and April 2015. We reviewed time to first relapse after treatment, co-medications, and side effects. RESULTS: A total of 102 children were treated with cyclophosphamide (79) and/or rituximab (42). Of these, 34 received cyclophosphamide prior to rituximab. Median time to first relapse was 7 months after cyclophosphamide and 14 months after rituximab. Documented side effects of cyclophosphamide included neutropenia, hair loss, and hemorrhagic cystitis (1). Rituximab was associated with an allergic reaction at infusion in two patients. CONCLUSIONS: Rituximab was used in children with the most difficult to treat FRSDNS, yet was associated with longer remission time and less side effects than cyclophosphamide. A randomized controlled trial is needed to directly compare these drugs.
Assuntos
Ciclofosfamida/uso terapêutico , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Rituximab/uso terapêutico , Criança , Ciclofosfamida/efeitos adversos , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Londres , Masculino , Síndrome Nefrótica/diagnóstico , Recidiva , Indução de Remissão , Estudos Retrospectivos , Rituximab/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Hemodialysis (HD) in children with a concomitant ventriculoperitoneal shunt (VPS) is rare. Registry data suggest that peritoneal dialysis with a VPS is safe, but little is known about HD in the presence of a VPS. METHODS: We performed a 10-year survey to determine the prevalence of a VPS, complications and outcome in children with a VPS on HD in 15 dialysis units from the 13 countries participating in the European Pediatric Dialysis Working Group. RESULTS: Eleven cases of HD with a VPS were reported (prevalence 1.33 %; 328 patient-months) and compared with prospective Registry data. The median age at start of dialysis was 9.6 [inter-quartile range (IQR) 1.0-15.0] years and median HD vintage was 2.4 (IQR 1.7-3.0) years. Dialysis was performed through a central venous line (CVL) and through an arteriovenous fistula in six and five children, respectively. Three CVL infections occurred in two children, but these children did not develop VPS infections or meningitis. Symptoms of hemodynamic instability were reported in six (55 %) children at least once per week, with hypotension or hypertension occurring in four of these children and nausea, vomiting and headaches occurring in two; four other children reported less frequent symptoms. Seizures on dialysis occurred in two children, at a frequency of less than once per month, with one child also experiencing visual disturbances. During follow-up (median 4.0; IQR 0.38-7.63 years), three children remained on HD and eight had a functioning transplant. No patients were switched to PD. CONCLUSIONS: Hemodialysis in children with a VPS is safe, but associated with frequent symptoms of hemodynamic instability. No episodes of VPS infection or meningitis were seen among the children in the survey, not even in those with CVL sepsis.
Assuntos
Derivação Arteriovenosa Cirúrgica/efeitos adversos , Cateterismo Venoso Central/efeitos adversos , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/terapia , Derivação Ventriculoperitoneal/efeitos adversos , Adolescente , Fatores Etários , Infecções Relacionadas a Cateter/diagnóstico , Infecções Relacionadas a Cateter/microbiologia , Cateterismo Venoso Central/instrumentação , Cateteres de Demora/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Criança , Pré-Escolar , Europa (Continente) , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Hipertensão/diagnóstico , Hipertensão/etiologia , Hipotensão/diagnóstico , Hipotensão/etiologia , Lactente , Transplante de Rim , Masculino , Insuficiência Renal Crônica/diagnóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Convulsões/diagnóstico , Convulsões/etiologia , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Derivação Ventriculoperitoneal/instrumentaçãoRESUMO
BACKGROUND: Idiopathic intracranial hypertension is a clinical condition with elevated intracranial pressure of uncertain etiology. Although various underlying causes are suspected and familial occurrence has also been reported, however, it still remains an unexplained phenomenon. CASE REPORT: We report the case of dizygotic siblings with a known CYP24A1 mutation resulting in chronic hypercalcemia and impairment of kidney function. At the same point in time both of them developed intracranial hypertension resistant to conservative therapy necessitating therefore ventriculoperitoneal shunt implantation. In both children magnetic resonance imaging showed slightly hypoplastic sinus transversus as the potential underlying cause. CONCLUSION: The simultaneous clinical presentation could be due to a genetic factor or might be a component of the underlying disease or the consequence of its treatment. Further cases and clinical experience are needed to clarify this issue.
Assuntos
Hipercalcemia/complicações , Hipercalcemia/genética , Hipertensão Intracraniana/complicações , Acetazolamida/uso terapêutico , Anticonvulsivantes/uso terapêutico , Encéfalo/patologia , Feminino , Frutose/análogos & derivados , Frutose/uso terapêutico , Humanos , Lactente , Hipertensão Intracraniana/diagnóstico , Hipertensão Intracraniana/genética , Imageamento por Ressonância Magnética , Irmãos , Topiramato , Gêmeos DizigóticosRESUMO
BACKGROUND: Pleural or pericardial effusions secondary to pleuro-peritoneal fistula (PPF) and pericardio-peritoneal fistula (PcPF) are rare but serious complications of peritoneal dialysis (PD). METHODS: We conducted a 10-year survey across all participating centres in the European Paediatric Dialysis Working Group to review the incidence, diagnostic techniques, therapeutic options and outcome of children on chronic PD with PPF and/or PcPF. RESULTS: Of 1506 children on PD there were ten cases (8 of PPF, 1 each of PcPF and PPF + PcPF), with a prevalence of 0.66%. The median age at presentation was 1.5 [inter-quartile range (IQR) 0.4-2.4] years, and nine children were <3 years. The time on PD before onset of symptoms was 4.3 (IQR 1.3-19.8) months. Eight children had herniae and seven had abdominal surgery in the preceding 4 weeks. Symptoms at presentation were respiratory distress, reduced ultrafiltration and tachycardia. PD was stopped in all children; three were managed conservatively and thoracocentesis was performed in seven (with pleurodesis in 3). PD was restarted in only three children, in two of them with success. CONCLUSION: In conclusion, PPF and PcPF are rare in children on chronic PD, but are associated with significant morbidity, requiring a change of dialysis modality in all cases. Risk factors for PPF development include age of <3 years, herniae and recent abdominal surgery.
Assuntos
Líquido Ascítico/patologia , Fístula/etiologia , Derrame Pericárdico/etiologia , Diálise Peritoneal/efeitos adversos , Derrame Pleural/etiologia , Criança , Pré-Escolar , Europa (Continente) , Feminino , Fístula/epidemiologia , Humanos , Incidência , Lactente , Falência Renal Crônica/terapia , Masculino , Derrame Pericárdico/epidemiologia , Derrame Pleural/epidemiologia , Prevalência , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Sudden blindness caused by anterior ischemic optic neuropathy (AION) is a rare complication for patients undergoing peritoneal dialysis (PD). Prognosis is generally poor, with AION commonly resulting in permanent visual loss. METHODS: We first describe four case reports of children with AION during PD treatment. We then review ten additional AION cases reported in the literature and compare these 14 affected patients with a control cohort of 59 non-affected patients in the Vienna PD registry. RESULTS: Significant risk factors for AION were identified as median age (4 vs. 27 months; p < 0.001), autosomal recessive polycystic kidney disease (28.6 vs. 3.4%; p = 0.01), anephric status (53.8 vs. 6.8%; p < 0.001) and low to normal blood pressure evidenced by the number of patients having to be treated with antihypertensive medications (14.3 vs. 62.7%; p = 0.01). Severe hypovolemia was reported in 50% of all cases. Outcome was visual loss with optic atrophy in nine patients; five patients had a good visual outcome. The major difference in treatment was a rapid bolus of saline within 12 h after the initial symptoms. CONCLUSIONS: Young age, autosomal recessive polycystic kidney disease, anephric status and hypotension are substantial risk factors for AION. Early hospitalization with vascular refilling within a few hours following onset of blindness leads to improved visual outcome.
Assuntos
Neuropatia Óptica Isquêmica/etiologia , Diálise Peritoneal/efeitos adversos , Adolescente , Fatores Etários , Pré-Escolar , Feminino , Humanos , Hipotensão/complicações , Lactente , Masculino , Neuropatia Óptica Isquêmica/terapia , Rim Policístico Autossômico Recessivo/complicações , Fatores de RiscoRESUMO
Recent studies suggest that the combination of caffeine-containing drinks together with alcohol might reduce the subjective feelings of alcohol intoxication-the so-called "masking effect". In this study, we aimed to review the effects of alcohol in combination with caffeine or energy drink with special focus on the "masking effect". Fifty-two healthy male volunteers were analysed concerning breath alcohol concentration and subjective sensations of intoxication using a 18 item Visual Analogue Scale in a randomised, double-blinded, controlled, four treatments cross-over trial after consumption of (A) placebo, (B) alcohol (vodka 37.5% at a dose of 46.5 g ethanol), (C) alcohol in combination with caffeine at a dose of 80 mg (equivalent to one 250 ml can of energy drink) and (D) alcohol in combination with energy drink at a dose of 250 ml (one can). Primary variables were headache, weakness, salivation and motor coordination. Out of four primary variables, weakness and motor coordination showed a statistically significant difference between alcohol and non-alcohol group, out of 14 secondary variables, five more variables (dizziness, alterations in sight, alterations in walking, agitation and alterations in speech) also showed significant differences due mainly to contrasts with the non-alcohol group. In none of these end points, could a statistically significant effect be found for the additional ingestion of energy drink or caffeine on the subjective feelings of alcohol intoxication. This within-subjects study does not confirm the presence of a "masking effect" when combining caffeine or energy drink with alcohol.
Assuntos
Intoxicação Alcoólica/psicologia , Álcoois/efeitos adversos , Cafeína/efeitos adversos , Bebidas Energéticas/efeitos adversos , Adulto , Álcoois/administração & dosagem , Cafeína/administração & dosagem , Voluntários Saudáveis , Humanos , Masculino , Adulto JovemRESUMO
BACKGROUND: Data on the immunization practices in pediatric chronic kidney disease (CKD) patients are scarce. The purpose of this study was to evaluate current vaccination practices for children on dialysis across European pediatric nephrology centers. METHODS: A total of 18 tertiary pediatric nephrology centers from 12 European countries were included in the study. The data on universal national immunization programs and immunization practices for children with chronic disease or risk were recorded from European Center for Disease Prevention and Control and the World Health Organization. The immunization practices and center protocols for monitoring antibody titers after vaccination in dialysis patients were obtained through a questionnaire. RESULTS: All centers included in the study recommended immunization against hepatitis B virus (HBV), diphtheria, tetanus, pertussis, Hemophilus influenzae type b (Hib), poliomyelitis, measles, mumps, rubella (MMR), and streptococcus pneumonia in dialysis patients. In 16 centers, dialysis patients were vaccinated against influenza virus annually. HBV protective antibody titers were measured in 17 centers (during dialysis period in 14 centers, during pre-renal transplantation preparations in 14 centers or in both times in 11 centers). Hepatitis A virus (HAV) was reported to be followed in 13 centers, in 8 centers during dialysis period, and in 11 centers during pre-RTx preparations. MMR and varicella-zoster virus (VZV) protective antibody titers were measured during the dialysis period or before renal transplantation (RTx) in 12 and 15 centers, respectively, and in 6 centers both titers were checked both times. CONCLUSION: There are variations in vaccination practice across Europe. Children with CKD, those undergoing dialysis, and transplant candidates should receive age-appropriate vaccinations before RTx as well as before the transition to adult nephrology clinics and antibody levels should be monitored to evaluate the immunization status before and after RTx.
Assuntos
Diálise Renal , Vacinação/estatística & dados numéricos , Adolescente , Anticorpos/análise , Criança , Pré-Escolar , Europa (Continente) , Humanos , Lactente , Nefrologia , Pediatria , Padrões de Prática Médica , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: To determine the utility of pre-implantation renal biopsy (PIB) to predict renal allograft outcomes. METHODS: This is a retrospective review of all patients that underwent PIB from January 2003 to December 2011 at the Great Ormond Street Hospital for Children in London, United Kingdom. Thirty-two male patients (56%) aged 1.5-16 years (median: 10.2) at the time of transplantation were included in the study and followed-up for 33 (6-78) months. The results were compared with 33 controls. RESULTS: The PIB showed normal histopathological findings in 13 patients (41%), mild chronic vascular changes in 8 (25%), focal tubular atrophy in one, moderate to severe chronic vascular change in 3, mild to moderate acute tubular damage in 6, and tissue was inadequate in one subject. Delayed graft function (DGF) was observed in 3 patients; 2 with vascular changes in PIB, and one with normal histopathological findings. Two subjects with PIB changes lost their grafts. The estimated glomerular filtration rate at 3-, and 6-months post-transplantation was lower in children with abnormal PIB changes compared with those with normal PIB. There was one case of DGF in the control group, and 4 children lost their grafts including the one with DGF. CONCLUSION: Pre-implantation renal biopsy can provide important baseline information of the graft with implications on subsequent medical treatment for pediatric renal transplant recipients.