I.H.S. Chan

Left Ventricular Filling Pressure by Doppler Echocardiography in Patients With End-Stage Renal Disease

Left ventricular hypertrophy and systolic dysfunction predict mortality in patients with end-stage renal disease. However, the prognostic value of left ventricular filling pressure has remained uncertain in this population. We evaluated whether the early mitral inflow velocity to peak mitral annulus velocity (E/Em) ratio, an estimate of left ventricular filling pressure by tissue Doppler imaging, has significant additional prognostic value to conventional echocardiographic parameters and other clinical and biochemical parameters in 220 patients with end-stage renal disease. The E/Em ratio was elevated (>15) in 62% of the patients. Multivariate analysis showed that an elevated E/Em ratio had the highest correlation with left ventricular volume index, followed by loss of residual glomerular filtration rate, increasing age, worsening ejection fraction, and diabetes. During the median follow-up of 48 months, the E/Em ratio emerged as an independent predictor of all-cause mortality (adjusted hazard ratio: 1.027; 95% CI: 1.003 to 1.051; P=0.026) and cardiovascular death (adjusted hazard ratio: 1.033; 95% CI: 1.002 to 1.065; P=0.035) in the multivariable Cox regression analysis. In addition, the E/Em ratio added significant incremental prognostic value for all-cause mortality (P=0.035) and cardiovascular death (P=0.035) beyond the standard clinical, biochemical, and dialysis parameters and echocardiographic measurements. In conclusion, the E/Em ratio displayed important additional long-term prognostic information above and beyond that of left ventricular mass and systolic function. Our data suggest that left ventricular filling pressure should be estimated during echocardiographic examination for additional prognostication in patients with end-stage renal disease.

Asthma and atopy are associated with DEFB1 polymorphisms in Chinese children

Human β-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.

Changes in serum leptin concentration after corticosteroid treatment in preterm infants.

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 (Td‐pre), 3 wk after commencement of the drug (Td‐end) and 2 wk after dexamethasone treatment had been stopped (Td‐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 (Twk–2), 5 (Twk–5) and 7 (Twk–7) wk of postnatal age. Serum leptin and insulin at Td–end were significantly increased, whereas plasma ACTH and serum cortisol were significantly suppressed compared with the pretreatment (Td–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 (Twk–5) and 7 (Twk–7) did not differ significantly from their respective levels at week 2 (Twk–2) in the non‐treatment group.

Suppression and recovery of the hypothalamic function after high-dose corticosteroid treatment in preterm infants.

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.