ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Upon activation, polymorphonuclear leucocytes (PMN) release bactericidal/permability-increasing protein, (BPI) from their azurophil granules. BPI selectively binds to the lipopolysaccharide (LPS) on gram-negative bacteria and induces their death. This study examined plasma BPI concentration levels in healthy newborns and in newborns with clinical sepsis, and the ability of PMN from preterm and term infants to release BPI. We also studied the release of myeloperoxidase (MPO), and the surface expression of adhesion molecule CD11b on PMN. In infants with clinical sepsis, plasma BPI concentration was higher, 27.8 &mgr;g/L [8.6–883; median (range)] (n= 11), than in healthy term infants 8.9 &mgr;g/L (3.9–179) (n= 17), and in adults 7.3 &mgr;g/L (0.7 –18.4) (n= 15);p= 0.014, Kruskal-Wallis. In preterm infants (n= 8), the ability of PMN to release BPIin vitroafter stimulation with PMA was 8.8, in term infants it was 15.9 (n= 29;p> 0.05 vs. preterm infants) and in adults 23.4 ng/106PMN (n= 15;p= 0.024 andp> 0.05 vs. preterm and term infants, respectively). The corresponding values of MPO were 20.0 ng/106(11.3–46.7) in preterms, 19.0 ng/106(2.2–223.7) in terms, and 27.8 ng/106(9.1–80.7) in adults;p= 0.67 between groups. In infants with clinical sepsis, CD11b level was higher, 292 RFU (234–403) than the basal CD11b expression levels in healthy newborn infants, 116 RFU (76–145);P= 0.0001. FMLP-stimulated PMN CD11b expressions in preterm cord blood, 1071 RFU (552–1286) and in term cord blood, 918 (567–1472) were on the same level, but lower than that in adult blood, 1592 (973–1946);p< 0.001, ANOVA. Our findings suggest that in preterm infants the ability to release BPI is lower than in adults and term infants. These findings suggest that premature neonates have an impaired ability to mobilize BPI, possibly contributing to their marked susceptibility to infections with Gram-negative bacteria.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The objective was to investigate any possible relationship between functional and structural vascular changes in women with low gestational age and/or low birth weight by analyzing the retinal vascular pattern in women with thoroughly documented blood pressure. Retinal vessel morphology was evaluated by digital image analysis of ocular fundus photographs in 47 subjects, aged 23–30 y. The women were allocated into three groups: 1) those born preterm and appropriate for gestational age (AGA), with a median gestational age at birth of 30 wk and a median birth weight of 1250 g (n= 14); 2) those born small for gestational age (SGA) but full term (median 40 wk), with a median birth weight of 2130 g (n= 17), and 3) those born full term, AGA, and with a median birth weight of 3640 g (n= 16). Women born preterm had significantly higher length index for arterioles compared with the other two groups (median 1.11 and 1.08, respectively,p= 0.005). In addition, the preterm-born women had significantly fewer number of vascular branching points compared with the controls (median 27 and 30, respectively,p= 0.03). The abnormal retinal vascularization observed in ex-preterm women together with an increased casual blood pressure observed in these subjects suggests that being born preterm does have effects on the vascular system that persist into adult life. In addition, it demonstrates that preterm birth seems to affect the vascular system both functionally and structurally, which, in adulthood, could result in a lower threshold for the development of vascular disease.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Epidemiologic studies suggest that intrauterine growth restriction (IUGR) can lead to impaired lung function, yet little information exists on the effects of IUGR on airway development. Our objectives were to characterize morphometrically effects of IUGR on airway structure in the fetus and to determine whether alterations persist into postnatal life. We used two groups of sheep, each with appropriate controls; a fetal group was subjected to IUGR by restriction of placental function from 120 to 140 d (term ∼147 d), and a postnatal group, killed 8 wk after birth, was subjected to IUGR from 120 d to birth at term. In both fetuses and postnatal lambs, IUGR did not alter lung weight relative to body weight. In IUGR fetuses, the luminal areas and basement membrane perimeters of the trachea and larger bronchi (generations 0–8, trachea = 0) were smaller than in controls. Airway wall areas, relative to basement membrane perimeters, were reduced in IUGR fetuses compared with controls, largely due to reduced areas of cartilage and epithelium. At 8 wk after birth, there were no significant differences in airway dimensions between IUGR and control lambs. However, the number of profiles of bronchial submucosal glands, relative to basement membrane perimeters, was lower in IUGR lambs than in controls and the area of epithelial mucin was increased. We conclude that restriction of fetal growth during late gestation impairs the growth of bronchial walls that could affect airway compliance in the immediate postnatal period. Although airway growth deficits are reversed by 8 wk, alterations in mucus elements persist.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The lung of the preterm infant is easily injured and an initial indication of the injury is an inflammatory response. Surfactant treatment and gentle ventilation will minimize the initiation and progression of injury. We asked if the initial lung injury response differed when preterm ventilated lambs were treated with complete natural sheep surfactant, a lipid extract of sheep surfactant, a surfactant used to treat RDS (Survanta®), or a synthetic surfactant containing recombinant SP-C (Venticute®). We used a gentle style of ventilation and a positive end expiratory pressure of 4 cmH20 to minimize injury. The surfactants were not distinguishable based on gas exchange, compliance or lung gas volumes over the 6h ventilation period. When compared with unventilated controls the ventilated lambs had increased protein and inflammatory cells in alveolar lavages. The cells from the alveolar lavages produced more H202, expressed more surface adhesion antigens and CD-14 receptors, and expressed more mRNA for the pro-inflammatory cytokines IL-1&bgr; and IL-8 than did cells from unventilated lungs. Lung tissue expressed primarily increased IL-6 mRNA relative to unventilated controls. However, there were no consistent differences in any of the inflammatory indicators between the different surfactant treated groups. Because endotoxin free natural surfactant containing SP-A was not superior to three other surfactants containing differing amounts of the surfactant proteins, additions of these proteins to clinical surfactants may not decrease the indicators of lung inflammation that accompany the initiation of ventilation of the preterm lung.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Respiratory syncytial virus (RSV) is the major respiratory tract pathogen in infancy. Host-related differences in susceptibility to severe RSV infection suggest that genetic factors may play a role. In this study, a candidate-gene approach was used to study whether the surfactant protein D (SP-D) gene polymorphism associates with severe RSV infection. DNA samples from 84 infants hospitalized for the treatment of RSV bronchiolitis and 93 healthy controls were analyzed. The controls were matched with the cases on the basis of sex, hospital district, date of birth (±2 wk) and gestational age at birth (±2 wk). Three biallelic SP-D gene polymorphisms were genotyped. Significant differences were observed in the SP-D allele frequencies for amino acid 11 between the RSV infants and their matched controls. The frequency of the allele coding for Met 11 (p= 0.033) was increased in the severe RSV group. The frequency of the homozygous genotype Met/Met for amino acid 11 was increased in the RSV group relative to the controls, whereas the heterozygous genotype tended to be less frequent among the RSV cases than in the matched controls. Conditional logistic regression analysis was used to study whether the confounders,i.e.smoking and number of children in the family, influence the association between the homozygous SP-D genotype for methionine 11 and the risk of RSV bronchiolitis. The results further confirmed this association (p= 0.028). To our knowledge, the present report provides the first evidence of a specific gene associated with susceptibility to severe RSV infection.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Highly discriminatory markers for celiac disease are needed to identify children with early mucosal lesions and for rapid follow-up. The aim of this study was to evaluate the potential of circulating anti-tissue transglutaminase (tTG) IgA and IgG antibodies in the diagnosis and follow-up of childhood celiac disease. An ELISA using recombinant human tTG was used to measure the levels of IgA and IgG anti-tTG antibodies in 226 serum samples from 57 children with biopsy-verified celiac disease, 29 disease control subjects, and 24 healthy control subjects. All samples were also analyzed for anti-endomysium antibodies (EMA). The levels of IgA and IgG anti-tTG antibodies correlated with the condition of the small intestinal villous structure and the serum levels of IgA EMA. All of the 25 serum samples obtained from untreated patients contained IgA anti-tTG antibodies, and 24 of 25 also had IgA EMA. Of the serum samples from 53 control children, two had IgA anti-tTG antibodies and two had IgA EMA. Children younger than 5 y of age with untreated celiac disease had the highest serum levels of both IgA and IgG anti-tTG. There was already an increase in IgA anti-tTG antibodies after 2 wk of gluten challenge (p< 0.01). Although the criteria-based diagnosis of childhood celiac disease still depends on histologic evaluation of intestinal biopsies, detection of anti-tTG antibodies provides useful complementary diagnostic information. The human recombinant tTG-based ELISA can be used as a sensitive and specific test to support the diagnosis and may also be used in the follow-up of treatment in childhood celiac disease.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The peroxisome biogenesis disorders (PBD) are a group of autosomal-recessive diseases with complex developmental and metabolic phenotypes, including the Zellweger spectrum and rhizomelic chondrodysplasia punctata. The diseases are caused by defects in peroxisomal matrix protein import and are characterized by the loss of multiple peroxisomal metabolic functions. In humans, 12 complementation groups have been identified, with complementation group 1 accounting for more than two thirds of all PBD patients. Mutations in thePEX1gene encoding a member of the AAA protein family of ATPases are responsible for the defects in this group, and a variety ofPEX1mutant alleles have been described. We characterized thePEX1gene mutations and associated haplotypes in a group of thoroughly documented Zellweger spectrum patients in complementation group 1 who represent the broad range of phenotypic variation. We compared the type of mutation with the age of survival, clinical manifestations, and biochemical alterations and found a close relationship between genotype and age of survival. Missense mutations cause a milder form of disease, whereas insertions, deletions, and nonsense mutations are associated with severe clinical phenotypes. Thus, knowing thePEX1gene mutation is helpful in predicting the course of disease in individual cases.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

We sought to determine whether a low-dose combination of a bile acid–binding resin (colestipol) with an hydroxymethylglutaryl CoA reductase inhibitor (pravastatin) would result in improved acceptability, compliance, and effectiveness in lipid-lowering compared with conventional therapy with a higher dose of a bile acid–binding resin only, with fewer side effects. We performed a randomized, crossover open-label clinical trial with two 18-wk medication regimens separated by an 8-wk washout period in 36 children and adolescents with familial hypercholesterolemia or familial combined hyperlipidemia. The regimens included colestipol 10 g/d (10 pills)versusa combination of colestipol 5 g/d with pravastatin 10 mg/d (six pills). All patients were maintained on a fat-reduced diet. Acceptability was better with the combination regimen. Mean compliance was similar and suboptimal (approximately 60%) with all medication components. Mean relative LDL cholesterol lowering was significantly better with the combination regimen (−17 ± 16%versus−10 ± 13%;p= 0.045), although insufficient to achieve recommended target values in the majority of patients on either regimen. Both regimens were equally free of adverse effects, with no important effect on chemistry or hematologic values. Patient-reported adverse effects were more common with the conventional-dose colestipol-only regimen. Compliance with medication regimens using the bile acid–binding resins is suboptimal, although combination with a low dose of a statin may result in better lipid lowering.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Recent studies have suggested that heat shock proteins (HSPs) are involved in the restoration of the cytoskeletal anchorage of Na,K-ATPase after renal ischemia. To determine their role in ischemic conditioning, we investigated whether cytoskeletal Na,K-ATPase was stabilized during repeat ischemia concurrent with 25-kD and 70-kD HSPs induction. Anesthetized rats either underwent single unilateral renal ischemia or were conditioned with bilateral renal ischemia and, after 18 h of reflow, were then subjected to repeat unilateral renal ischemia. Renal cortex was harvested, and effects of singleversusrepeat ischemia were compared by Triton X-100 extraction, by immunohistochemistry, and by anin vitroassay of Na,K-ATPase association with isolated cytoskeletal fractions. In contrast to single ischemia, repeat ischemia did not result in increased Triton X-100 extractability of Na,K-ATPase. Levels of 25-kD and 70-kD HSPs were significantly induced by ischemic conditioning and redistributed into the cytoskeletal fraction after single and repeat ischemia. Immunohistochemistry also showed significant disruption of Na,K-ATPase within proximal tubules only after a single episode of ischemia, whereas repeat ischemia did not alter the pattern of restored Na,K-ATPase localization in conditioned renal cortex. The preserved association of Na,K-ATPase with the cytoskeletal fraction of conditioned renal cortex was effectively abolishedin vitroby addition of antibodies against 25-kD or 70-kD HSP. These results suggest that 25-kD and 70-kD HSPs induced by ischemic conditioning stabilize the cytoskeletal anchorage of Na,K-ATPase during repeat renal ischemia.

ISSN:0031-3998    

出版商:OVID    

年代:2002

数据来源: OVID