RESUMEN
Cardiovascular disease (CVD) is the principal cause of mortality in chronic kidney disease (CKD) patients. Dyslipoproteinaemia is a common metabolic derangement in CKD and a traditional risk factor for CVD. This study investigates serum lipoprotein, especially small-dense low-density lipoprotein (sd-LDL), abnormalities in CKD patients. A total of 131 CKD patients (age: 59 +/- 12 years, male = 64) diagnosed according to Kidney Disease: Improving Global Outcomes, 2004 (KDIGO) and 121 age- and gender-matched control subjects (age: 58 +/- 6 years, male = 62) were recruited from Hong Kong and Macau. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C) and direct LDL-C were assayed enzymatically. In addition, sd-LDL, together with very low density and intermediate-density lipoproteins (VLDL and IDL) were measured by US Food and Drug Administration (FDA)-approved polyacrylamide gradient gel electrophoresis. Compared to controls, CKD patients showed significantly decreased TC, LDL-C, normal-size LDL and HDL-C with increased TG, VLDL, IDL and sd-LDL (all P < 0.01). The increased sd-LDL and decreased normal-size LDL fractions resulted in a significantly elevated sd-LDL:LDL ratio in CKD (P < 0.005). In contrast to the low TC and LDL-C, sd-LDL and sd-LDL:LDL ratio were significantly elevated in CKD. Thus, sd-LDL will be used increasingly for CVD risk assessment in CKD and other diseases that show lipoprotein derangement.
Asunto(s)
Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/epidemiología , Fallo Renal Crónico/sangre , Fallo Renal Crónico/epidemiología , Lipoproteínas LDL/sangre , Adulto , Anciano , Enfermedades Cardiovasculares/diagnóstico , Comorbilidad , Femenino , Hong Kong/epidemiología , Humanos , Fallo Renal Crónico/diagnóstico , Macao/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Medición de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Single-nucleotide polymorphism (SNP)-based genome-wide association study revealed that markers on chromosome 17q21 were linked to childhood asthma but not atopy in Caucasians, with the strongest signal being detected for the SNP rs7216389 in the ORMDL3 gene. Such association was unknown in Chinese. This study delineated the allele and genotype frequencies of 10 SNPs at chromosome 17q21, and investigated the relationship between these SNPs and asthma and plasma IgE in southern Chinese children. METHODS: Asthmatic children and non-allergic controls were recruited from pediatric clinics. Their plasma total and aeroallergen-specific IgE concentrations were measured by immunoassay. Ten SNPs on 17q21 region were genotyped by multiplex SNaPshot, and their genotype associations with asthma traits analyzed using multivariate regression. RESULTS: 315 patients and 192 controls were enrolled. The allele frequency for C allele of rs7216389 varied significantly from 0.232 in our controls, 0.389 in Han Chinese to 0.536 in Caucasians. Asthma diagnosis was associated with rs11650680 and five other SNPs including rs7216389 (P = 0.019-0.034), whereas atopy was associated only with rs11650680 (P = 0.0004). Linear regression revealed the covariates for plasma total IgE to be significant for rs11650680 (P = 0.008-0.0002). Haplotypic associations were found with atopy and increased plasma total IgE, with the respective odds ratios and 95% confidence intervals for TTTCCGTT haplotype to be 0.21 and 0.09-0.52 (P = 0.0002) and 0.41 and 0.18-0.90 (P = 0.025). CONCLUSION: Childhood asthma and atopy are associated with chromosome 17q21 in Chinese, but such association may involve genes other than ORMDL3 in this region.
Asunto(s)
Asma/genética , Cromosomas Humanos Par 17/genética , Predisposición Genética a la Enfermedad , Hipersensibilidad Inmediata/genética , Adolescente , Pueblo Asiatico , Estudios de Casos y Controles , Niño , Preescolar , Marcadores Genéticos , Estudio de Asociación del Genoma Completo , Humanos , Inmunoglobulina E/sangre , Proteínas de la Membrana/genética , Polimorfismo de Nucleótido SimpleRESUMEN
A recently identified interleukin (IL)-17-producing T-helper (Th) lymphocyte subset, which comprises Th17 cells producing hallmark cytokines IL-17A, IL-17F and IL-22, is involved in chronic inflammatory diseases. Elevated gene and protein expressions of IL-17 are manifested in allergic asthma. We further characterized the activation of Th17 cells in asthmatic patients. Peripheral blood mononuclear cells (PBMC) were purified from 31 asthmatic patients and 20 sex- and age-matched control subjects. The number of IL-17A secreting cells in peripheral blood was enumerated by enzyme-linked immunosorbent spot assay. Cell surface expression of Th17-related chemokine receptor CCR6, and plasma level of IL-17A, IL-17F and IL-22, and ex vivo production of IL-17A and IL-22 were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. The number of peripheral Th17 lymphocytes, expression of CCR6 on Th cells, and ex vivo IL-23, anti-CD3 and anti-CD28 induced production of IL-22 by PBMC were significantly elevated in asthmatic patients compared with control subjects (all p < 0.01). This clinical study further confirmed increased number of peripheral Th17 lymphocytes and cell surface expression of CCR6 receptors on Th cells in asthmatic patients. Pro-inflammatory cytokine IL-23 can exacerbate disease severity by activating pathogenic Th17 lymphocytes to release downstream inflammatory cytokine IL-22 in asthma.
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Asma/sangre , Interleucina-17/metabolismo , Leucocitos Mononucleares/metabolismo , Linfocitos T Colaboradores-Inductores/metabolismo , Adulto , Anciano , Anticuerpos Monoclonales/farmacología , Asma/metabolismo , Asma/patología , Antígenos CD28/inmunología , Complejo CD3/inmunología , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Humanos , Interleucina-17/sangre , Interleucina-23/farmacología , Interleucinas/sangre , Interleucinas/metabolismo , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/efectos de los fármacos , Masculino , Persona de Mediana Edad , Receptores CCR6/metabolismo , Linfocitos T Colaboradores-Inductores/citología , Adulto Joven , Interleucina-22RESUMEN
BACKGROUND: Asthma is a complex disease resulting from interactions between multiple genes and environmental factors. Study of gene-gene interactions could provide insight into the pathophysiology of asthma. METHODS: We investigated the interactions among 18 single-nucleotide polymorphisms in eight candidate genes for plasma total immunoglobulin E (IgE) concentration and peripheral blood (PB) eosinophil count in 298 Chinese asthmatic children and 175 controls. Generalized multifactor dimensionality reduction and generalized linear model were used to analyze gene-gene interactions for the quantitative traits. RESULTS: A significant interaction was found between R130Q in IL13 and I50V in IL4RA for plasma total IgE concentration, with a cross-validation (CV) consistency of nine of 10 and a prediction error of 41.1% (P = 0.013). Plasma total IgE concentration was significantly higher in the high-risk than the low-risk groups (P < 0.0001). For PB eosinophil count, significant interaction was found between C-431T in TARC and RsaI_in2 in FCERIB, with a CV consistency of nine of 10 and a prediction error of 40.2% (P = 0.009). PB eosinophil count was significantly higher in the high-risk group than the low-risk groups (P < 0.0001). Generalized linear model also revealed significant gene-gene interaction for the above two endophenotypes with P = 0.013 for plasma total IgE concentration and P = 0.029 for PB eosinophil count respectively. CONCLUSIONS: Our data suggest significant interactions between IL13 and IL4RA for plasma total IgE concentration, and this is the first report to show significant interaction between TARC and FCERIB for PB eosinophil count in Chinese asthmatic children.
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Asma/genética , Quimiocina CCL17/genética , Interleucina-13/genética , Subunidad alfa del Receptor de Interleucina-4/genética , Receptores de IgE/genética , Adolescente , Asma/sangre , Asma/diagnóstico , Estudios de Casos y Controles , Niño , Preescolar , China , Eosinofilia , Femenino , Humanos , Inmunoglobulina E/sangre , Masculino , Fenotipo , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple , Índice de Severidad de la Enfermedad , EspirometríaRESUMEN
G-401A polymorphism in RANTES promoter was associated with near-fatal asthma and atopic dermatitis in children. We studied whether gain-of-function mutations in RANTES gene were associated with asthma and atopy-related traits in Chinese children. Plasma total and aeroallergen-specific IgE concentrations were measured using micro-particle immunoassay and fluorescent enzyme immunoassay, respectively. Restriction fragment length polymorphism was used to genotype RANTES G-401A and C-28G. One hundred and twenty-nine asthmatic children and 66 controls were recruited. Their mean logarithmic plasma total IgE concentrations were 2.53 and 1.98, respectively (P<0.0001). RANTES G-401A was not associated with physician-diagnosed asthma (P = 0.408). However, RANTES G-401A allele was significantly associated with IgE sensitization to cat (odds ratio 2.35; 95% CI 1.15-4.77; P = 0.010). Those homozygous for -401A had higher plasma cat-specific IgE levels (P = 0.034). Subjects having -401A were also more likely to have mold-specific IgE (odds ratio 3.82; 95% CI 1.24-12.14; P = 0.007). On spirometry, those with -401A/ A had lower forced expiratory volume in 1-s (FEV1; P = 0.044). RANTES C-28G was not associated with any outcome in this study. In conclusion, the gain-of-function mutation at -401 of RANTES promoter is associated with sensitization to cat and mold allergens and FEV1 in Chinese children.
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Alérgenos/efectos adversos , Asma/genética , Quimiocina CCL5/genética , Polimorfismo Genético , Hipersensibilidad Respiratoria/genética , Adolescente , Niño , Preescolar , China , Femenino , Volumen Espiratorio Forzado/fisiología , Predisposición Genética a la Enfermedad , Humanos , Técnicas para Inmunoenzimas/métodos , Inmunoglobulina E/sangre , Masculino , Mutación/genética , Espirometría/métodosRESUMEN
This study aimed to investigate 1) the effect of maternal diabetes mellitus on ghrelin, resistin, leptin, and insulin in term newborns; 2) the interrelationship of these metabolic hormones in the early postnatal period; and 3) the association of the hormones with anthropometric parameters at birth. A total of 120 term newborns were prospectively enrolled and categorized into three groups: 40 were infants of nondiabetic mothers (group N), 42 were infants born to mothers with gestational diabetes on low energy dietary treatment (group D), and 38 were infants born to mothers with preexisting or severe gestational diabetes who required exogenous insulin for stabilization of blood sugar during pregnancy (group I). Plasma ghrelin and resistin were significantly lower in group I than in either group N or group D infants (P < 0.048). Plasma ghrelin and subscapular skinfold thickness were significantly higher in female than in male infants [plasma ghrelin: median (interquartile range), 3.8 (3.0-4.8) vs. 3.0 (2.4-4.0) ng/ml in females and males, respectively; P = 0.003; subscapular skinfold thickness: 4.9 (4.2-5.6) vs. 4.6 (3.9-5.2) mm; P = 0.03]. In group N, plasma ghrelin was significantly, but negatively, associated with birth weight (r = -0.31; P = 0.05) and body length (r = -0.33; P = 0.04), whereas in group I, plasma ghrelin was negatively correlated with plasma resistin (r = -0.37; P = 0.02). Plasma ghrelin and resistin are suppressed in infants of insulin-dependent diabetic mothers, suggesting that the metabolic hormonal system is probably operational in fetal and early postnatal life. A low circulating ghrelin concentration may be advantageous to these infants, because a reduction in appetite may prevent excessive weight gain postnatally and counterbalances the in utero anabolic effect of hyperinsulinism in poorly controlled diabetic mothers. The suppressive effect of insulin on resistin may partially explain the excess accumulation of adipose tissue in infants of diabetic mothers by reducing the inhibitory effect of resistin on adipogenesis. Female infants have significantly higher plasma ghrelin levels than male infants, suggesting that sexual dimorphism exists in utero. This study has also shown an association between some of the metabolic hormones in specific groups of infants and thus suggests that these hormones could have interacted in utero to regulate growth and fat storage during this critical period.
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Diabetes Mellitus Tipo 1/metabolismo , Hormonas Ectópicas/sangre , Hormonas Peptídicas/sangre , Embarazo en Diabéticas/metabolismo , Femenino , Ghrelina , Humanos , Recién Nacido , Insulina/sangre , Leptina/sangre , Masculino , Análisis Multivariante , Embarazo , Resistina , Factores SexualesRESUMEN
This prospective study aims to investigate the factors that influence the human CRH (hCRH) test and to provide reference ranges for plasma corticotropin (ACTH) and serum cortisol concentrations of the stimulation test in preterm, very low birth weight (VLBW) infants. Two hundred twenty-six hCRH tests were performed on 137 VLBW infants at d 7 and 14 of life. Plasma ACTH did not differ significantly between infants whose mothers did not receive antenatal corticosteroids (group 1) and those whose mothers received one or two doses (group 2) or more than two doses (group 3) of the drug. However, plasma ACTH levels at d 7 were found to be significantly higher in infants with severe lung disease who required intermittent positive-pressure ventilation (IPPV) or high-frequency oscillation ventilation (HFOV), compared with those who had milder pulmonary disease and did not require mechanical ventilation or needed only continuous positive airway pressure (CPAP) support (P < 0.011). A significantly higher rate of increase in plasma ACTH concentration at d 7 was also observed in infants whose mothers suffered from antepartum hemorrhage (P < 0.016). In contrast, infants in group 2 had significantly lower serum cortisol, compared with group 1 infants (P < 0.05), whereas group 3 infants did not have serum cortisol levels significantly different from those of patients in group 1 or 2. Significant positive correlation between serum cortisol at d 7 and the time interval between the last dose of antenatal dexamethasone and delivery was also observed in group 3 infants (r > 0.33, P < 0.045). In addition, infants who required IPPV or HFOV had significantly lower serum cortisol at d 7 (P < 0.0001), but this pattern of cortisol response was reversed on d 14, with infants requiring IPPV or HFOV having significantly higher serum cortisol (P < 0.036). The reference ranges for plasma ACTH and serum cortisol concentrations of the hCRH test at d 7 and 14 were also provided for group 1 and group 2 infants. This study demonstrates that even one or two doses of antenatal corticosteroids cause adrenal suppression in VLBW infants. Maternal antepartum hemorrhage also influences the pituitary response of preterm newborns in the first week of life. The change in the pattern of cortisol response in sick ventilated (IPPV or HFOV) infants during the first 2 wk of life suggests that a proportion of preterm infants may have inadequate adrenal response to stress in early postnatal life, but it is likely that rapid adaptation of the hypothalamic-pituitary-adrenal axis results in enhanced and more appropriate cortisol response by d 14. The percentile distribution of plasma ACTH and serum cortisol responses provides useful statistical reference data for interpretation of the hCRH test in VLBW infants and may also assist in facilitating the use of corticosteroids replacement therapy in cases with clinical manifestations suggestive of adrenal insufficiency.
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Corticoesteroides/efectos adversos , Insuficiencia Suprarrenal/inducido químicamente , Hormona Liberadora de Corticotropina , Recien Nacido Prematuro/sangre , Recién Nacido de muy Bajo Peso/sangre , Corticoesteroides/administración & dosificación , Glándulas Suprarrenales/fisiopatología , Insuficiencia Suprarrenal/diagnóstico , Insuficiencia Suprarrenal/fisiopatología , Hormona Adrenocorticotrópica/sangre , Envejecimiento , Femenino , Glucocorticoides/administración & dosificación , Humanos , Hidrocortisona/sangre , Recién Nacido , Enfermedades Pulmonares/terapia , Embarazo , Efectos Tardíos de la Exposición Prenatal , Valores de Referencia , Respiración ArtificialRESUMEN
Asthma is one of the most common chronic diseases in childhood; it is caused by a complex interaction between genetic factors and exposure to environmental allergens and irritants. Previous studies using the candidate gene approach showed that asthma was linked to a number of susceptibility genetic loci in Caucasian subjects. There are, however, only a few studies on asthma predisposition genes in the Chinese population. We studied the distribution of allele frequencies of I50V for the interleukin-4 receptor, two polymorphisms in intron 2 and exon 7 for the high-affinity IgE receptor (Fc epsilon RI-beta), R16G and E27Q for the beta(2)-adrenoceptor,and R275Q (824G/A) for CC chemokine receptor 3 in Chinese children.Seventy-six patients, with a mean age of 10.6 years, and 70 age- and sex-matched controls, were studied. Significantly more subjects in the asthma group had specific IgE antibodies against environmental allergens (P < 0.0001; odds ratio, 9.82). Genotyping of the six genetic markers showed that none of the six polymorphisms was associated with asthma in this cohort. The allele frequencies of I50V, R16G, and E27Q in our population were similar to those published for Asian subjects but not Caucasians. The R275Q substitution was a rare finding in our study and in the published reports. Our results demonstrate ethnic differences in polymorphisms of atopy candidate genes. Additional studies involving larger samples are required to investigate the association between asthma or atopy and the genotypes studied to date in Chinese children.
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Asma/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Hipersensibilidad Inmediata/genética , Estudios de Casos y Controles , Niño , China/epidemiología , Femenino , Genotipo , Humanos , Masculino , Polimorfismo GenéticoRESUMEN
OBJECTIVE: To assess the influence of circulating (basal) and stimulated plasma adrenocorticotrophin (ACTH) and serum cortisol on the duration of oxygen supplementation and development of chronic lung disease (CLD) in preterm, very low birthweight infants. METHODS: A total of 226 human corticotrophin releasing hormone stimulation tests were performed on 137 very low birthweight infants on days 7 and 14 in a tertiary neonatal centre. RESULTS: Multivariate regression analysis showed that the duration of oxygen supplementation was negatively associated with birth weight, but positively associated with alveolar-arterial oxygen gradient (A-aDO(2)) on the first day and with basal serum cortisol on day 14. In addition, the multivariate classification and regression trees model indicated that the two most useful indices for predicting CLD were clinical risk index for babies (CRIB) score (> 9) and peak serum cortisol (> 740 nmol/l) on day 14. The sensitivity, specificity, positive and negative predictive values of these factors for predicting CLD were 53%, 80%, 81%, and 70% respectively. CONCLUSIONS: The findings suggest that birth weight, severity of initial respiratory failure as reflected by the A-aDO(2) gradient, and continuing "stress" with persistent increase in serum cortisol on day 14 are significant risk factors associated with the duration of oxygen supplementation, whereas early pituitary-adrenal response (basal and peak plasma ACTH and serum cortisol on day 7) is not an independent risk factor. Although CRIB score in combination with peak serum cortisol on day 14 are useful predictors of CLD, the need to use a stimulation test and the relatively late timing of the forecast render these indices unattractive for routine clinical use.
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Hormona Adrenocorticotrópica/sangre , Hormona Liberadora de Corticotropina , Hidrocortisona/sangre , Enfermedades Pulmonares/sangre , Sistema Hipófiso-Suprarrenal/fisiopatología , Enfermedad Crónica , Métodos Epidemiológicos , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Enfermedades Pulmonares/fisiopatología , Masculino , Estimulación QuímicaRESUMEN
OBJECTIVES: A proportion of preterm, very low birthweight (VLBW, < 1500 g) infants may show inadequate adrenal response to stress in the immediate postnatal period. The human corticotrophin releasing hormone (hCRH) stimulation test was used to: (a) determine the relation between pituitary-adrenal response and systemic blood pressure in these infants; (b) characterise the endocrinological features of transient adrenocortical insufficiency of prematurity (TAP). STUDY DESIGN: A total of 226 hCRH tests were performed on 137 VLBW infants on day 7 and 14 of life in a tertiary neonatal centre. RESULTS: Basal, peak, and incremental rise in serum cortisol (Delta Cort(0-30)) on day 7 were associated significantly with the lowest systolic, mean, and diastolic blood pressures recorded during the first two weeks of life (r > 0.25, p < 0.005). These cortisol concentrations also correlated significantly but negatively with the maximum and total cumulative dose of dopamine (r > -0.22, p < 0.02), dobutamine (r > -0.18, p < 0.04), and adrenaline (r > -0.26, p < 0.004), total volume of crystalloid (r > -0.22, p < 0.02), and duration of inotrope treatment (r > -0.25, p < 0.006). Multivariate regression analysis of significant factors showed that the lowest systolic, mean, and diastolic blood pressures remained independently associated with serum cortisol (basal, peak, and Delta Cort(0-30)) on day 7. Hypotensive infants requiring inotropes (group 2) were significantly less mature and more sick than infants with normal blood pressure (group 1). The areas under the ACTH response curves were significantly greater in group 2 than in group 1, on both day 7 (p = 0.004) and day 14 (p = 0.004). In contrast, the area under the cortisol response curve was significantly greater in group 1 than in group 2 on day 7 (p = 0.001), but there was no significant difference between the two groups on day 14. In addition, serum cortisol at the 50th centile in hypotensive infants had high specificity and positive predictive value (0.80-0.93 and 0.81-0.89 respectively) for predicting early neonatal hypotension. CONCLUSIONS: This study characterises the fundamental endocrinological features of TAP: normal or exaggerated pituitary response; adrenocortical insufficiency; good recovery of adrenal function by day 14 of postnatal life. The results also provide the centiles of serum cortisol for hypotensive patients and infants with normal blood pressure, and show a significant relation between serum cortisol and blood pressure in VLBW infants.
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Insuficiencia Suprarrenal/complicaciones , Hormona Liberadora de Corticotropina , Hipotensión/complicaciones , Enfermedades del Prematuro/diagnóstico , Recién Nacido de muy Bajo Peso , Insuficiencia Suprarrenal/diagnóstico , Hormona Adrenocorticotrópica/sangre , Femenino , Humanos , Hidrocortisona/sangre , Hipotensión/diagnóstico , Recién Nacido , Recien Nacido Prematuro , Masculino , Análisis Multivariante , Estudios Prospectivos , Estadísticas no Paramétricas , Estimulación QuímicaRESUMEN
AIM: To characterise the change in serum and urinary bone markers in the early postnatal period, and to assess the effect of systemic corticosteroid on bone metabolism in preterm infants. METHODS: Bone formation was quantified by measurement of serum concentrations of bone specific alkaline phosphatase (BALP) and osteocalcin. Bone resorption was measured by monitoring creatinine adjusted urinary deoxypyridinoline (Dpd) concentration. Blood and urinary samples were collected from corticosteroid treated infants (n = 19) immediately before the start (T(d-pre)), three weeks after the start (T(d-end)), and two (T(d-post2)) and four weeks (T(d-post4)) after the end of the dexamethasone course. Untreated patients (n = 30) had specimens taken at week 3 (T(wk-3)), 6 (T(wk-6)), 8 (T(wk-8)), and 10 (T(wk-10)) of postnatal age. RESULTS: Serum concentrations of BALP and osteocalcin at T(d-end) were significantly lower than pretreatment levels and the levels at the corresponding time point (T(wk-6)) of the non-treatment group. In contrast, urinary Dpd concentration at T(d-end) was not significantly decreased compared with the pretreatment level. However, it was significantly lower than the urinary Dpd concentration at T(wk-6) of the non-treatment group. The rate of increase in lower leg length was significantly higher in the non-treatment group between weeks 3 and 6 than in the corresponding period during dexamethasone treatment in the corticosteroid group. CONCLUSION: Systemic corticosteroid causes appreciable suppression of serum BALP and osteocalcin and, to a lesser extent, urinary Dpd. The results suggest that corticosteroid inhibits bone growth mainly by decreasing bone formation.
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Antiinflamatorios/farmacología , Desarrollo Óseo/efectos de los fármacos , Dexametasona/farmacología , Glucocorticoides/farmacología , Enfermedades del Prematuro/fisiopatología , Enfermedades Pulmonares/fisiopatología , Fosfatasa Alcalina/sangre , Aminoácidos/orina , Biomarcadores/análisis , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/metabolismo , Recién Nacido de muy Bajo Peso , Enfermedades Pulmonares/metabolismo , Masculino , Osteocalcina/sangre , Estudios ProspectivosRESUMEN
INTRODUCTION: Nonradioactive cesium chloride (CsCl) is used by some alternative medicine advocates as a treatment for cancer. The therapy was proven to be neither safe nor effective. Chronic use of CsCl has resulted in cases with severe cardiotoxicity. CASE REPORT: A 65-year-old lady presented to our hospital's accident and emergency department with recurrent syncope attacks. Electrocardiogram monitoring showed QT prolongation and transient Torsades de Pointes (TDP) ventricular tachycardia. She was taking anticancer naturopathic drugs for 6 weeks before admission. One of her naturopathic drugs was subsequently confirmed containing 89% CsCl by weight. Besides conventional treatment of QT prolongation and TDP, the patient was given a 4-week course of oral Prussian blue to enhance gastrointestinal elimination of cesium. The serum half-life of cesium was reduced from 61.7 to 29.4 days after the use of Prussian blue. QT prolongation was normalized in 27 days. DISCUSSION: To our knowledge, this is the first published case of nonradioactive cesium poisoning treated with Prussian blue. A transient rise in serum cesium level was observed during Prussian blue therapy. Possible explanations for this observation include poor drug compliance during outpatient treatment and redistribution of cesium from body stores. CONCLUSION: Nonradioactive CsCl poisoning can result in severe cardiotoxicity with QT prolongation and TDP ventricular tachycardia. The key points in the management of nonradioactive cesium poisoning include cessation of cesium exposure, vigorous electrolytes replacement, and oral Prussian blue therapy.
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Antineoplásicos/envenenamiento , Cesio/envenenamiento , Cloruros/envenenamiento , Terapias Complementarias/efectos adversos , Torsades de Pointes/inducido químicamente , Anciano , Antídotos/administración & dosificación , Quimioterapia Combinada , Electrocardiografía , Electrólitos/administración & dosificación , Femenino , Ferrocianuros/administración & dosificación , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Taquicardia Ventricular/inducido químicamente , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/terapia , Torsades de Pointes/diagnóstico , Torsades de Pointes/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: High-dose systemic dexamethasone is effective in facilitating extubation of ventilated infants with bronchopulmonary dysplasia. Although the suppression and recovery of pituitary-adrenal response had been assessed after corticosteroid treatment in very low birth weight infants, its effect on hypothalamic function has not been longitudinally monitored. AIMS: This study was designed to assess the longitudinal hypothalamic response before, during and 4 weeks after a 3-week dose-tapering course of systemic dexamethasone treatment. PATIENTS AND METHODS: Twenty very low birth weight infants had blood collected for corticotropin-releasing hormone, ACTH and cortisol measurements immediately before starting dexamethasone (week 0), after receiving the maximum dose of treatment (week 1), at the end of the 3-week course (week 3) and 4 weeks after stopping corticosteroids (week 7). RESULTS: All circulating hormone concentrations were significantly suppressed during the treatment period at week 1 and week 3 compared with pretreatment concentrations at week 0 (p < 0.001). The recovery of pituitary function started early soon after week 1, whereas that of hypothalamus and adrenal functions started after the end of the dexamethasone course. Plasma ACTH concentration at week 7 had returned to the pretreatment level, but plasma corticotropin-releasing hormone (p < 0.05) and serum cortisol (p < 0.001) concentrations remained significantly suppressed. Partial recovery of hypothalamic and adrenal function was observed at week 7 (62 vs. 36% of their pretreatment levels, respectively). CONCLUSION: Our findings suggest that the hypothalamic function is suppressed during systemic corticosteroid treatment but partial recovery occurs 4 weeks after stopping therapy. Even in preterm infants, the hypothalamic-pituitary-adrenal axis behaves in a similar manner as in adult subjects and the pituitary function recovers earlier than that of hypothalamus and adrenals.
Asunto(s)
Dexametasona/administración & dosificación , Glucocorticoides/administración & dosificación , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Hormona Adrenocorticotrópica/sangre , Displasia Broncopulmonar/terapia , Hormona Liberadora de Corticotropina/sangre , Femenino , Humanos , Hidrocortisona/sangre , Sistema Hipotálamo-Hipofisario/fisiología , Recién Nacido , Recien Nacido Prematuro/sangre , Recién Nacido de muy Bajo Peso/sangre , Análisis de los Mínimos Cuadrados , Estudios Longitudinales , Masculino , Sistema Hipófiso-Suprarrenal/fisiología , Estudios Prospectivos , Desconexión del Ventilador/métodosRESUMEN
BACKGROUND: Asthma is caused by a complex interaction between multiple candidate genes and environmental factors. The Childhood Asthma Management Program reported lung function decline in a significant proportion of Caucasian asthmatic children, but such a relation has not been studied in other populations. Our group recently reported that interleukin-13 (IL13), interleukin-4 receptor-alpha and thymus and the activation-regulated chemokine interacted to influence asthma and raised plasma total IgE. However, there has not been any study that has addressed the genetic influences for longitudinal lung function growth. OBJECTIVE: We studied the longitudinal changes in spirometric variables in Chinese asthmatic children, and investigated the influence and interactions between eight different loci in six candidate genes as well as environmental factors affecting lung function growth in these children. METHODS: Spirometry was performed at baseline and study completion. Genotyping was performed by restriction fragment length polymorphism. Multi-factor dimensionality reduction (MDR) was used to detect any gene-gene or gene-environment interaction. RESULTS: We prospectively followed 131 Chinese children, aged 9.9 (3.0) years, for 4.5 (0.8) years. Their mean (standard deviation) baseline forced expiratory volume in 1 s (FEV1) was 98.6 (20.6)% of predicted, and FEV1 to forced vital capacity (FVC) ratio was 77.8 (11.3)%. FEV1 and FVC increased by 210 (115) and 248 (148) mL/year during this study, and these changes were significantly larger among males (P<0.0001). Univariate analysis revealed a significant association between annual FEV1 change and C1570T of signal transducer and activator of transcription 6 gene (STAT6; P=0.009). Linear regression confirmed this finding (P=0.041). Using MDR, we detected a significant 3-locus interaction between IL13 R130Q, ADRB2 R16G and STAT6 C1570T for determining change in FVC (P=0.045). CONCLUSION: Our data suggest that STAT6 may influence lung function growth in asthmatic children. We also found significant interactions among several atopy-related genetic polymorphisms for influencing FVC change.
Asunto(s)
Asma/fisiopatología , Pulmón/crecimiento & desarrollo , Pulmón/fisiopatología , Capacidad Vital/genética , Adolescente , Pueblo Asiatico/genética , Niño , China , Ambiente , Femenino , Humanos , Interleucina-13/genética , Masculino , Polimorfismo de Nucleótido Simple , Receptores Adrenérgicos beta 2/genética , Factor de Transcripción STAT6/genéticaRESUMEN
BACKGROUND: Cyclooxygenase-2 (COX-2) plays essential roles in inflammation. Previous studies have suggested associations between prostaglandin-endoperoxide synthase 2 (PTGS2) polymorphisms and prostaglandins production in asthma. OBJECTIVE: We have investigated the effects of Chinese tagging single nucleotide polymorphisms (SNPs) of PTGS2 on asthma traits in 299 Chinese asthmatic children and 175 controls. METHODS: Plasma total and allergen-specific IgE were measured by enzyme immunoassay. PTGS2.8473T-->C in the 3'-untranslated region of exon 10 and three tag SNPs covering most of the variations in PTGS2 haplotypes in Chinese were genotyped by restriction fragment length polymorphism. RESULTS: Among the four SNPs, only PTGS2.8473 showed significant association with asthma (P = 0.034) and atopy (P = 0.005 when compared with non-atopic controls; P = 0.023 with all controls). Carriers of the C allele had a 1.5-fold (95% confidence interval: 1.01-2.30) risk of developing asthma than those homozygous for the T allele. Multivariate regression revealed significant correlations between PTGS2.8473 and forced expiratory volume in 1 s (FEV(1); P = 0.002) and peak expiratory flow rate (PEFR; P = 0.001) with age and gender adjusted. Patients with the C allele of PTGS2.8473 had significantly lower FEV(1) (median: 90.0%vs 98.0%; P = 0.0047) and PEFR (70.0%vs 73.5%; P = 0.0065) than those homozygous for the T allele. No significant association between plasma total and allergen-specific IgE and these SNPs or with their haplotypes was found. CONCLUSIONS: PTGS2.8473 polymorphism is associated with asthma, atopy and lung function but not plasma IgE in Chinese children. This may help to explore the pharmacogenetics of COX-2 inhibitors.
Asunto(s)
Asma/genética , Ciclooxigenasa 2/genética , Hipersensibilidad Inmediata/genética , Proteínas de la Membrana/genética , Polimorfismo de Nucleótido Simple , Adolescente , Alelos , Estudios de Casos y Controles , Niño , Preescolar , China/epidemiología , Genotipo , Humanos , Inmunoglobulina E/sangre , Epidemiología Molecular , Valor Predictivo de las Pruebas , Pruebas de Función RespiratoriaRESUMEN
Patients on maintenance peritoneal dialysis (PD) are frequently complicated with volume overload. In this study, we sought to evaluate troponin T testing alone or in combination with echocardiographic measures in predicting cardiovascular congestion in PD patients. This was a prospective study of 222 chronic PD patients with echocardiography and measurement of serum troponin T carried out at baseline. Patients were followed for 3 years or until death. The end point was first episode of cardiovascular congestion. Troponin T emerged as an independent predictor of cardiovascular congestion (hazard ratio, 2.98, 95% confidence intervals (CI), 1.19-7.42) in a multivariable Cox regression model, including also left ventricular mass index (LVMi) and ejection fraction (EF). Patients with troponin T>median (0.06 microg/l) and EFAsunto(s)
Biomarcadores/sangre
, Cardiopatías/sangre
, Fallo Renal Crónico/terapia
, Diálisis Peritoneal Ambulatoria Continua/efectos adversos
, Troponina T/sangre
, Función Ventricular Izquierda
, Adulto
, Anciano
, Ecocardiografía
, Femenino
, Estudios de Seguimiento
, Cardiopatías/diagnóstico por imagen
, Cardiopatías/epidemiología
, Insuficiencia Cardíaca/sangre
, Insuficiencia Cardíaca/diagnóstico por imagen
, Insuficiencia Cardíaca/epidemiología
, Humanos
, Hipertrofia Ventricular Izquierda/sangre
, Hipertrofia Ventricular Izquierda/diagnóstico por imagen
, Hipertrofia Ventricular Izquierda/epidemiología
, Fallo Renal Crónico/epidemiología
, Masculino
, Persona de Mediana Edad
, Valor Predictivo de las Pruebas
, Pronóstico
, Modelos de Riesgos Proporcionales
, Estudios Prospectivos
, Factores de Riesgo
, Disfunción Ventricular Izquierda/sangre
, Disfunción Ventricular Izquierda/diagnóstico por imagen
, Disfunción Ventricular Izquierda/epidemiología
RESUMEN
Human beta-defensin (HBD)-1 is constitutively expressed in the airway, and hBD-1 plays crucial roles in innate immunity against respiratory pathogens. Asthma was associated with DEFB1 polymorphisms in Caucasians. This study investigates whether three single nucleotide polymorphisms (SNPs) in 5'-untranslated region of DEFB1 are associated with asthma phenotypes in Chinese children. Subjects aged 5-18 years were recruited from general pediatric clinics. Plasma IgE concentrations were measured by immunoassays. DEFB1 SNPs were characterized by restriction fragment length polymorphism. In all, 305 asthmatics and 156 controls were recruited. For asthma diagnosis, atopy and plasma total IgE, higher percentages of subjects with these outcomes had the minor alleles -20A and -52G (P = 0.041-0.0002). For log-transformed total IgE, the covariate was positive and significant for G-20A under recessive model (P = 0.001) and for G-52A under both recessive and codominant models (P = 0.008 and 0.035). The recessive model covariate was also positive and significant (P = 0.020) for C-44G on peripheral blood eosinophil count. The GCA haplotype of DEFB1 was significantly associated with asthma (odds ratio (95% confidence interval): 1.64 (1.05-2.57); P = 0.029). These results suggest that DEFB1 is a candidate gene for asthma and atopy in children.
Asunto(s)
Asma/genética , Hipersensibilidad Inmediata/genética , Polimorfismo Genético , beta-Defensinas/genética , Adolescente , Pueblo Asiatico/genética , Asma/inmunología , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Hipersensibilidad Inmediata/inmunología , Masculino , Fenotipo , Carácter Cuantitativo Heredable , Población Blanca/genéticaRESUMEN
The chemokine response of eight children with serologically confirmed severe acute respiratory syndrome (SARS) was longitudinally monitored. All had raised plasma interferon gamma inducible protein (IP-10) concentrations, which suggested an active type 1 T-helper lymphocyte mediated immune response. High circulating IP-10 levels could facilitate viral clearance and might play a role in assisting the recovery of the patients.
Asunto(s)
Quimiocinas/metabolismo , Síndrome Respiratorio Agudo Grave/sangre , Quimiocina CCL2/metabolismo , Quimiocina CCL5/metabolismo , Quimiocina CXCL10 , Quimiocina CXCL9 , Quimiocinas CXC/metabolismo , Niño , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Interferón gamma/metabolismo , Estudios Longitudinales , Linfocitos T/metabolismoRESUMEN
Leukotriene E4 (LTE(4)) is elevated in adults with atopic dermatitis (AD). We evaluated whether urinary LTE(4) as a noninvasive marker correlates with clinical indices of disease activity in children with AD. AD patients aged 18 years or younger were eligible for inclusion in the study. Disease severity over the preceding 3 days was evaluated by the SCORing Atopic Dermatitis (SCORAD) index. Severity of AD over the past 12 months was evaluated by the Nottingham Eczema Severity Score (NESS) in Chinese. Urinary LTE(4) concentration was measured by competitive enzyme immunoassay. One hundred and twenty-six children with AD (82 boys and 44 girls) and 45 controls were recruited. The mean +/- SD urinary log-transformed LTE(4) concentration in AD patients and controls was 2.94 +/- 0.32 and 2.62 +/- 0.20 pg/mg creatinine, respectively (P < 0.0001). SCORAD significantly correlated with NESS (r = 0.681, P < 0.0001). There were significant correlations between urinary LTE(4) concentration and overall SCORAD score (r = 0.270, P = 0.002) and its extent (r = 0.185, P = 0.038) and intensity components (r = 0.247, P = 0.005), but not with NESS. When compared with mild AD, urinary LTE(4) concentrations were higher in patients with moderate-to-severe disease (P = 0.049). Urinary LTE(4) measurement is noninvasive and may be useful in supplementing the SCORAD for following longitudinal changes in AD severity in children. However, the practical value of this assay in a clinical setting remains to be determined.
Asunto(s)
Dermatitis Atópica/orina , Leucotrieno E4/orina , Adolescente , Biomarcadores/orina , Niño , Creatinina/orina , Dermatitis Atópica/diagnóstico , Femenino , Humanos , Masculino , Índice de Severidad de la EnfermedadRESUMEN
UNLABELLED: The aim of this study was to investigate the effect of postnatal systemic dexamethasone on serum leptin, insulin and hormones of the hypothalamic-pituitary-adrenal (HPA) axis in preterm, very low birthweight (VLBW) infants. Nineteen VLBW infants who received a 3 wk dose tapering course of dexamethasone for treatment of bronchopulmonary dysplasia were prospectively enrolled. Blood for hormone assays was collected immediately before the start of the dexamethasone course (T(d-per)), 3 wk after commencement of the drug (T(d-end)) and 2 wk after dexamethasone treatment had been stopped (T(d-post)). In addition, 28 VLBW infants who participated in a concurrent longitudinal leptin study within the same period but did not receive corticosteroid had their serum leptin and insulin concentrations serially monitored. Blood specimens for the latter group of infants were obtained at 2 (T(wk-2)), 5 (T(wk-5)) and 7 (T(wk-7)) wk of postnatal age. Serum leptin and insulin at T(d-end) were significantly increased, whereas plasma ACTH and serum cortisol were significantly suppressed compared with the pretreatment (T(d-pre)) levels in the corticosteroid group (p < 0.0001 for leptin and insulin; p < 0.05 and p < 0.001 for ACTH and cortisol, respectively). In contrast, serum leptin and insulin at weeks 5 (T(wk-5)) and 7 (T(wk-7)) did not differ significantly from their respective levels at week 2 (T(wk-2)) in the non-treatment group. CONCLUSION: The administration of systemic corticosteroid resulted in significant increases in serum leptin and insulin, but marked suppression of hormones of the HPA axis. The effect of dexamethasone on the "adipoinsular" and HPA axes was transient and reversible. The adipoinsular axis in preterm infants is likely to be functional and active at an early stage of human development, and leptin may regulate energy balance in VLBW infants in the early postnatal period. Corticosteroids may, through the adipoinsular axis or its associated pathways, mediate in the regulation of body weight in preterm neonates.