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1.
Pediatr Nephrol ; 23(2): 297-305, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18004597

RESUMO

Dyslipidaemia exists frequently after renal transplantation (RTx) and promotes atherosclerosis. In this study, we examined the association between daily intake of nutrients and serum lipids after paediatric RTx. We studied 45 children with acceptably functioning kidney grafts and adequately completed food records at a median age of 10.6 years (range 4.3-17.2 years), a median 5.2 years (range 1.0-11.0) after RTx, and 178 healthy controls at a median age of 9.0 years (range 3.2-18.7 years). Serum total cholesterol (TC), triglyceride, and apolipoprotein B concentrations were higher in the RTx patients than in the controls (P < 0.001), despite similar dietary intakes of saturated and polyunsaturated fats, and cholesterol. Both the RTx patients and controls ingested a low amount of polyunsaturated fats [mean (SD) percent of total calories (E%) 4.8 (1.3) and 4.6 (1.5), respectively] and an excessive amount of saturated fats [mean (SD) E% 14.4 (2.4) and 14.1 (2.8), respectively]. In multiple regression analyses, dietary fibre was negatively associated with serum TC concentration. The standard deviation score for body mass index was negatively associated with serum concentration of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein diameter, and positively with serum triglyceride concentration. In addition, dietary total fat intake was positively associated with serum HDL-C. In conclusion, the higher prevalence of dyslipidaemia in our paediatric RTx patients than in the controls was not explained by the diet. However, the type of fat consumed implicates the counselling for a healthier dietary lifestyle, with an increase in the ingestion of polyunsaturated fats and a decrease in that of saturated fats.


Assuntos
Gorduras na Dieta , Dislipidemias/etiologia , Transplante de Rim , Complicações Pós-Operatórias , Adolescente , Apolipoproteínas B/sangue , Criança , Pré-Escolar , Colesterol/sangue , Comorbidade , Registros de Dieta , Dislipidemias/epidemiologia , Finlândia/epidemiologia , Humanos , Lactente , Prevalência , Fatores de Risco , Triglicerídeos/sangue
2.
Rhinology ; 45(4): 286-91, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18085022

RESUMO

OBJECTIVE: To find out whether previous adenoidectomy is associated with asthma, allergic symptoms or allergen-specific IgE antibodies. RECRUITMENT AND METHODS: We recruited 213 paediatric patients admitted for elective tonsillectomy and 155 paediatric controls. Using a structured questionnaire, we recorded their respiratory symptoms, allergies, bronchial asthma and environmental factors. Serum IgE antibodies against respiratory allergens were screened. Patients were divided into those previously adenoidectomised (n = 100) or not adenoidectomised (n = 113). RESULTS: Any allergy (p = 0.007) and non-antibiotic allergy diagnosed by a doctor (p = 0.015), and asthma (p = 0.015) were more common among adenoidectomised than non-adenoidectomised children under the age of seven. Between ages 7 and 11, neither any kind of allergy nor asthma were associated with earlier adenoidectomy. In the oldest age group (12 to 17), only antibiotic allergy was more common in adenoidectomised children. Recurrent otitis media (p < 0.001) and recurrent sinusitis (p = 0.007) were more common in adenoidectomised children. After controlling for recurrent respiratory infections, doctor-diagnosed allergy remained significantly associated with adenoidectomy in the youngest age group. Prevalence of specific IgE did not differ between the patient groups, or between school-aged patients and controls. CONCLUSIONS: Our results suggest that hypersensitivity disorders and infections may share aetiological factors. However, as adenoidectomised children of any age did not have higher levels of specific IgE, it seems possible that allergy is either clinically over-diagnosed or insufficiently detected by serology among young adenoidectomised children.


Assuntos
Adenoidectomia , Asma/imunologia , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Modelos Logísticos , Masculino , Otite Média/imunologia , Recidiva , Sinusite/epidemiologia
4.
Pediatr Transplant ; 11(5): 481-90, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17631015

RESUMO

The levels and protein/lipid compositions of major lipoprotein particles of 19 pediatric cardiac transplant recipients (4-18 yr of age) were studied in this prospective, open clinical follow-up study before and at one yr of pravastatin therapy (10 mg/day). The recipients were grouped into those with (n = 6; group A) and those without (n = 13; group B) angiographically detectable vasculopathy. Twenty-one pediatric non-transplant controls were studied at baseline. At baseline, the group A recipients had 29% lower HDL-C concentrations (p = 0.031) and 29% higher apoB-100/apoA-I ratios (p = 0.034) than the group B recipients. At one yr of pravastatin, the respective figures were 29% (p = 0.013) and 33% (p = 0.005). Compared with the healthy pediatric controls, the transplant recipients had significantly higher serum TG before pravastatin [median (range): 1.3 mmol/L (0.6-3.2) vs. 0.7 mmol/L (0.3-2.4), p = 0.0002] and at one yr [1.3 mmol/L (0.5-3.5) vs. 0.7 mmol/L (0.3-2.4), p = 0.0004]. The baseline apoB-100/apoA1 ratios of the recipients were 33% higher (p = 0.005). In conclusion, low HDL-C and high apoB-100/apoA-I ratio were associated with angiographically detectable vasculopathy. Even though pravastatin effectively lowered the TC and LDL-C and improved compositional properties of LDL and HDL(2) particles, it failed to normalize the elevated TG and, in some patients, to prevent the progression of transplant vasculopathy.


Assuntos
Anticolesterolemiantes/efeitos adversos , HDL-Colesterol/deficiência , Doença das Coronárias , Transplante de Coração , Pravastatina/efeitos adversos , Adolescente , Anticolesterolemiantes/uso terapêutico , Biomarcadores/sangue , Criança , Pré-Escolar , HDL-Colesterol/sangue , HDL-Colesterol/efeitos dos fármacos , Colorimetria , Angiografia Coronária , Doença das Coronárias/sangue , Doença das Coronárias/etiologia , Doença das Coronárias/prevenção & controle , Feminino , Seguimentos , Rejeição de Enxerto/sangue , Rejeição de Enxerto/prevenção & controle , Insuficiência Cardíaca/cirurgia , Humanos , Lactente , Masculino , Complicações Pós-Operatórias , Pravastatina/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento , Ultracentrifugação
5.
J Pediatr ; 149(2): 241-7, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16887443

RESUMO

OBJECTIVE: To evaluate the efficacy of early prednisone therapy in preventing renal and treating extrarenal and renal symptoms in Henoch-Schönlein purpura (HSP) in a placebo-controlled trial. STUDY DESIGN: A total of 171 patients (84 treated with prednisone and 87 receiving placebo) were included and followed up for 6 months. The endpoints were renal involvement at 1, 3, and 6 months and healing of extrarenal symptoms. The analyses were performed on an intent-to-treat basis. RESULTS: Prednisone (1 mg/kg/day for 2 weeks, with weaning over the subsequent 2 weeks) was effective in reducing the intensity of abdominal pain (pain score, 2.5 vs 4.8; P = .029) and joint pain (4.6 vs 7.3; P = .030). Prednisone did not prevent the development of renal symptoms but was effective in treating them; renal symptoms resolved in 61% of the prednisone patients after treatment, compared with 34% of the placebo patients (difference = 27%; 95% confidence interval = 3% to 47%; P = .024). CONCLUSIONS: The general use of prednisone in HSP is not supported, but patients with disturbing symptoms may benefit from early treatment, because prednisone reduces extrarenal symptoms and is effective in altering (but not preventing) the course of renal involvement.


Assuntos
Anti-Inflamatórios/uso terapêutico , Vasculite por IgA/tratamento farmacológico , Prednisona/uso terapêutico , Dor Abdominal/diagnóstico , Dor Abdominal/epidemiologia , Adolescente , Anti-Inflamatórios/efeitos adversos , Artralgia/diagnóstico , Artralgia/epidemiologia , Criança , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Vasculite por IgA/epidemiologia , Nefropatias/diagnóstico , Nefropatias/epidemiologia , Masculino , Prednisona/efeitos adversos , Prevalência , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
6.
Br J Clin Pharmacol ; 61(6): 706-15, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16722833

RESUMO

AIMS: Our aim was to investigate associations between the single nucleotide polymorphisms (SNPs) in the SLCO1B1 (encoding OATP1B1) and ABCB1 (encoding P-glycoprotein) genes with the pharmacokinetics and efficacy of pravastatin in children with heterozygous familial hypercholesterolaemia (HeFH) and in paediatric cardiac transplant recipients. METHODS: Twenty children with HeFH (aged 4.9-15.6 years) and 12 cardiac transplant recipients (aged 4.4-18.7 years and receiving triple immunosuppressive medication) who had participated in previous pharmacokinetic and pharmacodynamic studies with pravastatin were genotyped for the -11187G > A and 521T > C SNPs in the SLCO1B1 gene and for the 2677G > T/A and 3435C > T SNPs in the ABCB1 gene. RESULTS: Two HeFH patients with the -11187GA genotype had a 81% lower peak plasma pravastatin concentration (Cmax) (difference in means -13.9 ng ml(-1), 95% CI -21.1, -6.7; P < 0.001) and a 74% smaller area under the plasma concentration-time curve (AUC0, infinity) (-25.3 ng ml(-1) h, 95% CI -35.6, -15.0; P < 0.0001) and significantly greater increase in high density lipoprotein (HDL) cholesterol after 2 months treatment with pravastatin than patients with the reference genotype. No significant differences were seen in the pharmacokinetics or effects of pravastatin between HeFH patients with the SLCO1B1 521TC and 521TT genotypes. The cardiac transplant recipients with the SLCO1B1 521TC genotype (n = 3) had a 46% lower Cmax (-67.7 ng ml(-1), 95% CI -135.7, 0.3; P = 0.055) and 62% lower AUC(0,24 h) (-228.5 ng ml(-1) h, 95% CI -402.7, -54.3; P = 0.016) and a shorter half-life (t1/2) (0.9 +/- 0.1 vs. 1.3 +/- 0.4 h, P = 0.015) of pravastatin than those with the reference genotype. Decreases in total and low-density lipoprotein cholesterol by pravastatin were significantly smaller, and the increase in HDL-cholesterol was greater in the transplant recipients with the 521TC genotype compared with patients with the 521TT reference genotype. CONCLUSIONS: In children with HeFH and in paediatric cardiac transplant recipients receiving immunosuppressive medication, the -11187G > A and SLCO1B1 521T > C SNPs were associated with decreased plasma concentrations of pravastatin. These differences are opposite to those seen previously in healthy adults. The mechanisms underlying these phenomena are unclear and warrant further study.


Assuntos
Transplante de Coração , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Transportadores de Ânions Orgânicos/genética , Pravastatina/uso terapêutico , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Adolescente , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Hiperlipoproteinemia Tipo II/genética , Transportador 1 de Ânion Orgânico Específico do Fígado , Masculino , Polimorfismo Genético/genética , Pravastatina/farmacocinética , Resultado do Tratamento
7.
J Pediatr ; 148(2): 241-6, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16492436

RESUMO

OBJECTIVE: To assess causes for insufficient cholesterol-lowering response to pravastatin and plant stanol esters in children with heterozygous familial hypercholesterolemia (HeFH). STUDY DESIGN: Nine of 16 children with HeFH who had not reached normocholesterolemia (< or =194 mg/dL [< or =5 mmol/L]) by 1 year after treatment (40 mg pravastatin and plant stanol ester) were called nonresponders. The 7 remaining children were responders. Serum noncholesterol sterol ratios (10(2) x mmol/mol of cholesterol), surrogate estimates of cholesterol absorption (cholestanol, campesterol, sitosterol) and synthesis (desmosterol and lathosterol), were studied at study baseline (on plant stanol esters) and during combination therapy with pravastatin and plant stanol esters. RESULTS: Pravastatin decreased the serum levels of cholesterol and cholesterol synthesis markers, and increased the ratios of cholesterol absorption markers. Compared with the responders, the nonresponders had higher study baseline (on plant stanol esters) serum cholesterol concentrations (299 +/- 39 vs 251 +/- 35 mg/dL [7.7 +/- 1.0 vs 6.5 +/- 0.9 mmol/L]; P <.001) and higher respective ratios of campesterol (371 +/- 99 vs 277 +/- 67 10(2) x mmol/mol of cholesterol; P = .049) and sitosterol (176 +/- 37 vs 126 +/- 24 10(2) x mmol/mol of cholesterol; P = .008). The higher the ratio of cholestanol at study baseline, the smaller the 1-year percent reduction in cholesterol (r = .556; P = .025). CONCLUSIONS: Pravastatin treatment increases the markers of cholesterol absorption and decreases those of cholesterol synthesis in HeFH during simultaneous inhibition of cholesterol absorption. Combined inhibition of cholesterol absorption and synthesis may not normalize serum lipids in those patients with the highest cholesterol levels, especially if signs of enhanced cholesterol absorption are detectable.


Assuntos
Anticolesterolemiantes/uso terapêutico , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Fitosteróis/uso terapêutico , Pravastatina/uso terapêutico , Adolescente , Criança , Colestanol/sangue , Colesterol/análogos & derivados , Colesterol/sangue , Colesterol/metabolismo , Desmosterol/sangue , Feminino , Heterozigoto , Humanos , Masculino , Fitosteróis/sangue , Sitosteroides/sangue , Triglicerídeos/sangue
8.
Transplantation ; 81(3): 327-34, 2006 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-16477216

RESUMO

BACKGROUND: Hypercholesterolemia after organ transplantation is common. Previously, we observed higher serum total cholesterol (TC) concentrations in our pediatric kidney than liver or heart transplant recipients. To find an explanation to the observed difference, our kidney recipients' cholesterol synthesis and absorption efficiency was compared to those of liver and heart recipients. METHODS: Serum noncholesterol sterol ratios (10 x mmol to the mol of TC, surrogate estimates of hepatic cholesterol synthesis and intestinal absorption) were studied in 50 pediatric kidney, 25 liver and 12 heart transplant recipients without diabetes or cholestasis, and in 29 controls. RESULTS: The kidney recipients had lower Delta-cholesterol (P=0.031), similar lathosterol and higher desmosterol ratios (markers of cholesterol synthesis) (P=0.020), and similar campesterol and sitosterol ratios (markers of cholesterol absorption) when compared to the controls. The liver recipients had lower campesterol ratios than the kidney recipients and controls (P=0.002). Glomerular filtration rates were not associated with the ratios of noncholesterol sterols. Multivariate analysis showed markers of cholesterol synthesis to be lower and absorption to be higher in the kidney than the liver or the heart transplant recipients. Weight-adjusted dosages of immunosuppressive agents were associated with some ratios of noncholesterol sterols and cholestanol though these varied between the transplant recipient groups. CONCLUSIONS: Serum TC concentration in kidney recipients was not significantly associated with absorption efficiency or synthesis of cholesterol, though kidney transplantation was associated with low synthesis and high absorption efficiency of cholesterol. Immunosuppressive therapy with cyclosporine and methylprednisolone may modulate absorption efficiency and synthesis of cholesterol.


Assuntos
Colesterol/sangue , Transplante de Coração , Transplante de Rim , Transplante de Fígado , Adolescente , Criança , Pré-Escolar , Colesterol/biossíntese , Gorduras na Dieta/administração & dosagem , Feminino , Humanos , Masculino , Esqualeno/sangue , Esteróis/sangue
9.
Kidney Int ; 67(5): 2046-55, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15840056

RESUMO

BACKGROUND: Dyslipidemia is common after solid organ transplantation. We have described hypertriglyceridemia in about 50% of our pediatric kidney, and in about 30% of our liver recipients. The aim of the present study was to find out whether this post-transplantation hypertriglyceridemia after pediatric solid organ transplantation is associated with insulin resistance and the occurrence of small, dense low-density lipoprotein (LDL). METHODS: Fifty kidney and 25 liver recipients (aged 4 to 18 years) on triple immunosuppression, and 181 control children participated in the study for an average of 5.3 and 6.4 years after kidney and liver transplantation (range 1 to 11 years), respectively. Homeostasis model assessments for insulin resistance (HOMA) were calculated and fasting lipoprotein lipid profile, apolipoprotein A-I and B concentrations, LDL particle diameter, and indices of LDL susceptibility to copper-induced oxidation determined. RESULTS: Kidney patients had significantly higher serum total, high-density, and low-density lipoprotein cholesterol, triglyceride, apolipoprotein A-I and B concentrations than liver patients or control subjects (P < 0.003 for all). HOMA indices higher than the 95th percentile of Canadian normal children were seen in 50.0% of kidney (of liver 41.2%) recipients younger than 11 years, and in 27.3% of older recipients (of liver 37.5%). Smaller sized LDL or LDL of increased oxidizability was not more frequent in patients than in control children. CONCLUSION: Pediatric kidney recipients had significantly higher lipid and insulin concentrations than healthy control children. Combined hyperlipidemia and features of the dysmetabolic syndrome were common in children after kidney and liver transplantation. However, no small, dense LDL, or LDL prone to oxidation was seen in either group.


Assuntos
Resistência à Insulina , Transplante de Rim/efeitos adversos , Transplante de Rim/fisiologia , Lipoproteínas LDL/sangue , Transplante de Fígado/efeitos adversos , Transplante de Fígado/fisiologia , Adolescente , Glicemia/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/etiologia , Técnicas In Vitro , Lipídeos/sangue , Lipoproteínas LDL/química , Masculino , Oxirredução , Tamanho da Partícula
10.
J Clin Endocrinol Metab ; 90(4): 1942-52, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15657370

RESUMO

Heterozygous familial hypercholesterolemia (HeFH) is associated with elevated cholesterol levels and early-onset atherosclerosis. We assessed the efficacy and safety for up to 2 yr of pravastatin treatment in 19 girls and 11 boys (age range, 4.1-18.5 yr) with HeFH. Pravastatin was started at 10 mg/d, with a forced titration by 10 mg at 2, 4, 6, and 12 months until the target cholesterol level [< or =194 mg/dl (< or =5 mmol/liter)] was reached. By 2, 4, 6, 12, and 24 months of treatment, the total cholesterol levels had, respectively, decreased by 19, 20, 23, 27, and 26%, and the low-density lipoprotein cholesterol levels had decreased by 25, 27, 29, 33, and 32% compared with the dietary baseline values. Seventeen percent of patients had lipid deposits (carotid plaque, xanthomas, or corneal arcus) at baseline, and 27% had deposits at 1 yr. The side effects were mild, and no clinically significant elevations in alanine aminotransferase, creatine kinase, or creatinine were seen. Growth and pubertal maturation remained normal in all subjects. In conclusion, pravastatin treatment was safe and well tolerated. The efficacy in children with slight or moderate hypercholesterolemia was satisfactory, but in children with severe hypercholesterolemia, it was insufficient.


Assuntos
Hiperlipoproteinemia Tipo II/tratamento farmacológico , Pravastatina/uso terapêutico , Tendão do Calcâneo/diagnóstico por imagem , Adolescente , Hormônio Adrenocorticotrópico/sangue , Artérias Carótidas/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Seguimentos , Crescimento/efeitos dos fármacos , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/fisiopatologia , Lipídeos/sangue , Masculino , Cooperação do Paciente , Pravastatina/efeitos adversos , Estudos Prospectivos , Desenvolvimento Sexual , Ultrassonografia
11.
J Heart Lung Transplant ; 23(4): 418-26, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15063401

RESUMO

BACKGROUND: Increased concentrations of serum triglyceride and low-density lipoprotein (LDL) cholesterol are common after heart transplantation (HTx). These abnormalities may promote transplant vascular disease and atherosclerosis, especially if LDL is small, dense, and oxidized. There have been no previous studies of LDL particle size and LDL susceptibility to oxidation in children after HTx. METHODS: Twenty-three HTx recipients (aged 3-19 years) who received triple-drug immunosuppression therapy after HTx and 181 controls within the same age range participated in the study. Total, high-density lipoprotein, and LDL-cholesterol concentrations; triglyceride concentration, and glucose and insulin concentrations during oral glucose tolerance tests were determined an average of 3 years after HTx (range, 1-7 years). Moreover, we determined serum lipoprotein (a) concentration, apolipoprotein E phenotype, LDL particle size, and indices of LDL susceptibility to copper-induced oxidation in 12 HTx recipients. RESULTS: We found hypertriglyceridemia in 56.5% and hyperinsulinemia in 30.4% of patients. Triglyceride concentration and body mass index were associated significantly with insulin concentration (p < 0.008 for both). Low-density lipoprotein particle size, LDL susceptibility to in vitro oxidation, and lipoprotein (a) concentrations did not differ significantly between HTx patients and controls. Low-density lipoprotein particle size was associated inversely with cyclosporine through level (Neoral, r = -0.59, p = 0.045), whereas weight-adjusted dosage of cyclosporine correlated positively with longer lag time of LDL oxidation (r = 0.69, p = 0.013). CONCLUSIONS: Hypertriglyceridemia and hyperinsulinemia were common in children receiving triple-drug immunosuppression therapy after HTx. Increased cyclosporine through concentration was associated with small LDL particle size but did not increase LDL susceptibility to oxidation.


Assuntos
Glicemia/metabolismo , Colesterol/sangue , Transplante de Coração/fisiologia , Lipoproteínas LDL/química , Triglicerídeos/sangue , Adolescente , Adulto , Apolipoproteínas A/sangue , Apolipoproteínas B/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Feminino , Teste de Tolerância a Glucose , Humanos , Terapia de Imunossupressão , Insulina/sangue , Masculino , Oxirredução , Tamanho da Partícula
12.
Clin Pharmacol Ther ; 75(1): 101-9, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14749696

RESUMO

BACKGROUND: In adults, pravastatin reduces the development and progression of transplant vasculopathy, the main long-term risk after cardiac transplantation. The pharmacokinetics of pravastatin is not known in children taking calcineurin inhibitors. Our aim was to determine the single-dose pharmacokinetics and short-term safety of pravastatin in children undergoing regular triple-drug immunosuppressive therapy after cardiac transplantation. METHODS: Nineteen pediatric cardiac transplant recipients (aged 4.4 to 18.9 years) receiving triple immunosuppression therapy consisting of methylprednisolone (19 patients), cyclosporine (INN, cyclosporin) (17 patients) or tacrolimus (2 patients), and azathioprine (18 patients) or mycophenolate mofetil (1 patient) ingested a single 10-mg dose of pravastatin, and plasma pravastatin concentrations were measured up to 24 hours. Subsequently, the patients took 10 mg pravastatin orally once daily for 8 weeks. The lipid-lowering effect and the safety of pravastatin therapy were studied. RESULTS: The mean peak plasma concentration (C(max)) of pravastatin was 122.2 +/- 88.2 ng/mL (range, 11.4-305.0 ng/mL), and the area under the plasma concentration-time curve of pravastatin from 0 to 10 hours [AUC(0-10)] was 264.1 +/- 192.4 ng.h/mL (range, 30.8-701.6 ng.h/mL). These C(max) and AUC(0-10) values are nearly 10-fold higher than the corresponding values reported in hypercholesterolemic children in the absence of immunosuppressive therapy. The time of peak concentration (t(max)) of pravastatin was 1.1 +/- 0.4 hours (range, 0.5-2 hours), and the mean elimination half-life (t(1/2)) was 1.2 +/- 0.3 hours (range, 0.7-2.2 hours); these parameters were similar to those in the hypercholesterolemic children. By 8 weeks of treatment, the concentration of serum total cholesterol decreased by 13% (P =.005), low-density lipoprotein cholesterol by 27% (P <.0001), and triglycerides by 6% (not significant, P =.28); the concentration of high-density lipoprotein cholesterol increased by 7% (not significant, P =.30). No clinically significant increases in serum ALT, creatine kinase, or creatinine levels were observed. CONCLUSIONS: The plasma concentrations of pravastatin in pediatric cardiac recipients receiving triple immunosuppressive medication are nearly 10-fold higher than in hypercholesterolemic children after the same pravastatin dose. However, the short-term therapy of pravastatin was well tolerated and effective in lowering serum cholesterol levels in cardiac recipients.


Assuntos
Anticolesterolemiantes/farmacologia , Inibidores de Calcineurina , Transplante de Coração , Imunossupressores/administração & dosagem , Ácido Micofenólico/análogos & derivados , Pravastatina/farmacologia , Administração Oral , Adolescente , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/sangue , Anticolesterolemiantes/farmacocinética , Área Sob a Curva , Azatioprina/administração & dosagem , Criança , Pré-Escolar , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Ciclosporina/administração & dosagem , Interações Medicamentosas , Feminino , Humanos , Masculino , Metilprednisolona/administração & dosagem , Ácido Micofenólico/administração & dosagem , Pravastatina/administração & dosagem , Pravastatina/sangue , Pravastatina/farmacocinética , Tacrolimo/administração & dosagem , Triglicerídeos/sangue
13.
Transpl Int ; 17(3): 109-19, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14749918

RESUMO

Although dyslipidemia is common after solid organ transplantation (Tx), there are few long-term studies in children. We investigated the prevalence of dyslipidemia up to 5 years after Tx in 125 children on triple immunosuppression with one of three different well-functioning grafts, kidney, liver, and heart, and 181 controls. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) concentrations were measured annually. Low-density lipoprotein cholesterol concentrations were also calculated. The risk factors for dyslipidemia were determined at 3 years. There was a high prevalence of hypertriglyceridaemia in all three groups, 50% in the kidney transplantation (KTx) and heart transplantation (HTx) groups and 30% in the liver transplantation (LTx) group. In addition, 50% of KTx patients had high TC. In the Tx groups taken together, the following independent associations were observed: KTx and high pre-Tx TC were associated with high TC, high trough concentration of blood cyclosporine with low HDL-C, and older age at Tx accounted for higher TG. Dyslipidemia, especially hypertriglyceridaemia, was common 3-5 years after Tx. The aetiology is multifactorial and depends on the transplanted organ.


Assuntos
Transplante de Coração/fisiologia , Transplante de Rim/fisiologia , Lipídeos/sangue , Transplante de Fígado/fisiologia , Estatura , Índice de Massa Corporal , Colesterol/sangue , LDL-Colesterol/sangue , Quimioterapia Combinada , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Humanos , Hipertrigliceridemia/epidemiologia , Imunossupressores/uso terapêutico , Lactente , Masculino , Complicações Pós-Operatórias/epidemiologia , Fatores de Tempo , Triglicerídeos/sangue
14.
Clin Pharmacol Ther ; 74(2): 178-85, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12891228

RESUMO

BACKGROUND: Pravastatin is a widely used statin in adults, but its pharmacokinetics in children is not known. Our aim was to determine the single-dose pharmacokinetics and the lipid-lowering effect and safety of short-term administration of pravastatin in children. METHODS: Twenty children (age range, 4.9-15.6 years) with heterozygous familial hypercholesterolemia ingested a single dose of 10 mg pravastatin. Plasma concentrations of pravastatin were measured for up to 10 hours. The patients then took 10 mg pravastatin orally once daily for 8 weeks. The concentration of serum lipids and safety laboratory parameters were measured before and after 8 weeks of treatment. RESULTS: The mean peak plasma concentration (C(max)) of pravastatin was 15.7 ng/mL (range, 1.6-55.0 ng/mL), and the mean time to reach C(max) was 1.4 hours (range, 0.5-4 hours). The mean elimination half-life of pravastatin was 1.6 hours (range, 0.85-4.2 hours). The area under the plasma concentration-time curve of pravastatin ranged from 5.7 to 58.9 ng. h/mL (mean value, 26.6 ng. h/mL). By 8 weeks of treatment, the serum concentration of total cholesterol had decreased 18% (P <.0001); low-density lipoprotein cholesterol, 21% (P <.0001); and triglycerides, 18% (not significant, P =.18). The concentration of high-density lipoprotein cholesterol had increased 8% (not significant, P =.13). Few transient adverse events occurred. No increases in serum alanine aminotransferase, creatine kinase, or creatinine level were observed. CONCLUSIONS: The pharmacokinetic and pharmacodynamic profile of pravastatin in children is similar to that reported for adults. In the short term, the daily dose of 10 mg pravastatin was well tolerated and moderately effective in decreasing the serum cholesterol concentration. However, further studies are needed on the long-term safety and efficacy of pravastatin in children.


Assuntos
Anticolesterolemiantes/farmacocinética , Anticolesterolemiantes/uso terapêutico , Pravastatina/farmacocinética , Pravastatina/uso terapêutico , Adolescente , Área Sob a Curva , Criança , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Hiperlipoproteinemia Tipo II/metabolismo , Masculino , Espectrometria de Massas por Ionização por Electrospray , Triglicerídeos/sangue
15.
J Pediatr ; 142(5): 524-31, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12756385

RESUMO

OBJECTIVE: To show whether the ratios of squalene and cholesterol precursor sterols to cholesterol and cholestanol and plant sterols to cholesterol change differently in plasma and especially in the red cells of hypercholesterolemic children during consumption of plant stanol and sterol ester spreads. STUDY DESIGN: In a randomized, double-blind, crossover study, hypercholesterolemic children (n = 23) consumed low-fat plant stanol and sterol ester spreads for 5-week periods separated by a 5-week washout period. Plasma and red cell lipids, squalene, and noncholesterol sterols were measured before and at the end of each period. RESULTS: The plant stanol and sterol ester spreads lowered plasma total (-9% and -6%, respectively) and low-density lipoprotein (-12% and -9%) cholesterol but had no effect on red cell cholesterol, high-density lipoprotein cholesterol, or plasma triglycerides. The ratios of plasma and red cell sitosterol and campesterol to cholesterol decreased by 32% to 36% (P <.001) with the plant stanol ester and increased by 40% to 52% (P <.001) with the sterol ester spread. CONCLUSIONS: Consumption of plant sterols increases and consumption of plant stanols decreases the ratios of plant sterols to cholesterol in red cells of hypercholesterolemic children proportionately to the respective changes in plasma.


Assuntos
Eritrócitos/metabolismo , Hipercolesterolemia/sangue , Fitosteróis/sangue , Sitosteroides/sangue , Sitosteroides/farmacologia , Criança , Pré-Escolar , HDL-Colesterol/sangue , HDL-Colesterol/efeitos dos fármacos , LDL-Colesterol/sangue , LDL-Colesterol/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Margarina , Fitosteróis/farmacologia , Fatores de Tempo , Triglicerídeos/metabolismo
16.
Am J Clin Nutr ; 77(1): 51-5, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12499322

RESUMO

BACKGROUND: The data on lipid metabolism in allergic children is limited. OBJECTIVE: We investigated lipid and sterol metabolism in young children whose diets were restricted because of food allergy. DESIGN: Children in group A [n = 21; mean (+/- SD) age: 1.78 +/- 0.73 y] were allergic to fish, eggs, and either cow milk or cereals; those in group B (n = 31, aged 1.45 +/- 0.58 y) were allergic to fish, eggs, and both cow milk and cereals. Cholesterol precursor and plant sterol to cholesterol ratios (10(2) x micro mol/mmol cholesterol) and apolipoprotein E phenotype distributions were analyzed in 36 subjects. The control group for cholesterol precursor and plant sterol measurements consisted of 18 healthy age-matched children. RESULTS: The mean serum cholesterol concentration was 3.6 +/- 0.6 mmol/L, and HDL cholesterol was 1.03 +/- 0.3 mmol/L in group A. Corresponding values in group B were 3.4 +/- 0.7 and 1.09 +/- 0.2 mmol/L. The daily cholesterol intake was low: 61.3 +/- 36.0 mg in group A and 50.7 +/- 48.5 mg in group B. Cholesterol precursor plant sterol concentrations were significantly higher in allergic subjects than in control subjects. CONCLUSIONS: Allergic children with restricted diets have a low intake of cholesterol and relatively low serum cholesterol concentrations. Dietary intake of plant sterols was obviously increased because of supplementation with rapeseed oil, which is rich in plant sterols, leading to elevated plant sterol concentrations. Plant sterols may have inhibited cholesterol absorption, which in turn stimulated cholesterol synthesis in compensation, also explaining the increased precursor sterol ratios in serum in our subjects.


Assuntos
Colesterol/sangue , Hipersensibilidade Alimentar/metabolismo , Metabolismo dos Lipídeos , Fitosteróis/metabolismo , Estudos de Casos e Controles , Pré-Escolar , Finlândia , Hipersensibilidade Alimentar/diagnóstico , Humanos , Lactente , Lipídeos/sangue , Fitosteróis/sangue
17.
Pediatr Nephrol ; 17(6): 438-43, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12107809

RESUMO

Forty-one children <5 years of age at kidney transplantation (TX) were investigated for growth, bone age, and renal function up to 7 years ( n=26) after TX. All children received triple immunosuppression, including alternate-day corticosteroid treatment. Catch-up growth was seen in 81% of 30 children without growth hormone (GH) treatment. Children <2 years of age without GH had a mean height standard deviation score (hSDS) of -1.1+/-0.8 at TX and -1.1+/-0.5 at 7 years; children between 2 and 5 years improved their hSDS from -1.9+/-0.9 to -0.4+/-0.8 ( P<0.0001). The hSDS at TX correlated inversely with the DeltahSDS from TX to 7 years ( r=-0.80, P=0.0002). Glomerular filtrations rate (GFR) at 5 years post TX correlated with the subsequent growth rate from 5 to 7 years TX ( r=0.58, P=0.01). Catch-up growth was seen in all 11 children receiving GH. Their mean hSDS improved from -2.5+/-0.9 to -1.1+/-0.9 ( P<0.0001). In the majority of children receiving a kidney graft in early life, triple immunosuppression with alternate-day steroids can ensure catch-up growth. In children <5 years of age at TX, growth is predicted better by the degree of stunting than by age.


Assuntos
Transplante de Rim , Rim/crescimento & desenvolvimento , Determinação da Idade pelo Esqueleto , Estatura , Peso Corporal , Pré-Escolar , Feminino , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Hormônio do Crescimento/uso terapêutico , Humanos , Rim/fisiopatologia , Masculino
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