IL-15和非特异性炎症病变

0引言IL-15在类风湿性关节炎、炎性肠病、多发性硬化、牛皮癣、系统性红斑狼疮、肾炎及川崎病的发病过程中起重要作用,也参与肝脏和肺部的某些炎症病变。目前认为IL-15作为免疫治疗药物有广阔的发展前景。Grabstein等人于1994年首先发现IL-15是一种能促进T细胞生长和分化的细胞因子,主要由天然免疫细胞如巨噬细胞产生。生物活性广泛,在炎症性疾病中有其独特的作用。本文现将近年来的有关研究进展综述如下:

拉米夫定/干扰素-α联合治疗围生期感染乙肝的免疫耐受患儿:一项初步研究

Objective:To investigate whether combining the antiviral effect of lamivudine with the immune-boosting action of interferon-alpha(IFN-α)is effective in treating hepatitis B virus(HBV)“immunotolerant”children.Study design:Twen tythree children(8 boys;mean age,10 years)infected during the first year of life(17 Asian,21 with normal aminotransferase levels,15 with HBV-DNA > 1000 pg/mL by hybridization and all with mild histologic changes)were treated with l amivudine(3 mg/kg)for 8 weeks alone and then lamivudine(3 mg/kg)-and IFN-α(5 MU/m2,3 times weekly)in combination for 10 months.Results:Seventy-eight percent became HBV-DNA negative at the end of treatment,5(22%)seroconverted to anti-HBe,4(17%)of whom achieved complete viral control,becoming persis tently HBsAg negative and anti-HBs positive.None had YMDD mutations.The viral status of the patients has not changed after a median follow-up of 40 months(range,36 to 48).Conclusions:This pilot study suggests that lamivudine pretrea tment followed by a combination of lamivudine and IFN-αcan induce complete vir al control in HBV immunotolerant children,hitherto considered poor responders.

保守疗法治疗先天性气管狭窄的效果:一项循证长期随访研究

Background/Purpose:Surgery has been the management of choice for severe congenital tracheal stenosis (CTS). The role of conservative management of CTS however is not clear. The aim of this study is to characterize the natural history of CTS,review the radiologic evidence of tracheal growth,and evaluate the clinical outcome and selection criteria of conservative management of CTS. Methods:A retrospective study was carried out on 22 consecutive children with symptomatic CTS admitted into a single institution between 1982 and 2001. The patients were categorized into operation (n = 11) and observation(n = 11) groups. Six patients of the observation group were followed up with serial computed tomography scan. Their tracheal growth was compared with that of healthy children of the same age. Results:The mortality rates of observation and operation groups were 9%and 27%,respectively,although the latter group consisted of more severely affected patients. The pathologic categorization of the CTS influenced the survival rates (P = 0.046,χ2),with the long segment type having the worst prognosis (67%). Serial computed tomography scans of 6 conservatively managed patients revealed that all stenotic tracheas continued to grow (P = .039,2-tailed paired Student’s t test). Of the 6 stenotic tracheas,5 grew at a faster-than normalrate,and the stenotic tracheal diameters approached those of normal diameters by the age of 9 years. Conclusions:The management of patients with symptomatic CTS should be individualized. A selected group of patients with CTS can be safely managed nonoperatively.

肠系膜静脉-左肝门静脉旁路治疗脾肾分流引起的脑病

Surgically created portosystemic shunts can alleviate the symptoms of bleeding from gastric and esophageal varices and improve the hematologic consequences of hypersplenism in patients with portal hypertension. However, the diversion of mesenteric venous blood away from the liver can result in encephalopathy. In this report, we describe a case in which encephalopathy caused by a proximal splenorenal shunt was reversed by the restoration of portal flow to the liver by a mesenteric-to-left portal vein bypass operation.

随机对照临床试验:奥利司他对肥胖青少年体重和身体组分的影响

The prevalence of overweight and obesity in children and adolescents is increasing rapidly. In this population, behavioral therapy alone has had limited success in providing meaningful, sustained weigh t reduction, and pharmacological treatment has not been extensively studied. Objective: To determine the efficacy and safety of orlistat in weight management of adolescents. Design, Setting, and Patients: Multicenter, 54- week (August 2000- October 2002), randomized, double-blind study of 539 obese adolescents (aged 12- 16 years; body mass index [BMI]≥ 2 units above the 95th percentile) at 32 centers in the United States and Canada. Interventions: A 120- mg dose of orlistat (n=357) or placebo (n=182) 3 times daily for 1 year, plus a mildly hypocaloric diet (30% fat calories), exercise, and behavioral therapy. Main Outcome Measures: Change in BMI; secondary measures included changes in waist and hip circumference, weight loss, lipid measurements, and glucose and insulin responses to oral glucose challenge. Results: There was a decrease in BMI in both treatment groups up to week 12, thereafter stabilizing with orlistat but increasing beyond baseline with placebo. At the end of the study, BMI had decreased by 0.55 with orlistat but increased by 0.31 with placebo (P=.001). Compared with 15.7% of the placebo group, 26.5% of participants taking orlistat had a 5% or higher decrease in BMI (P=.005); 4.5% and 13.3% , respectively, had a 10% or higher decrease in BMI (P=.002). At study end, weight had increased 0.53 kg with orlistat and 3.14 kg with placebo (P<.001). Dual-energy x-ray absorptiometry showed that this difference was explained by changes in fat mass. Waist circumference decreased in the orlistat group but increased in the placebo group (- 1.33 cm vs + 0.12 cm; P<.05). Generally mild to moderate gastrointestinal tract adverse events occurred in 9% to 50% of the orlistat group and in 1% to 13% of the placebo group. Conclusions: In combination with diet, exercise, and behavioral modification, orlistat statistically significantly improved weight management in obese adolescents compared with placebo. The use of orlistat for 1 year in this adolescent population did not raise major safety issues although gastrointestinal adverse events were more common in the orlistat group.

乳酸杆菌GG作为泻药乳果糖附加物治疗儿童便秘是无效的:一双盲、安慰剂对照随机试验

Objective: To determine if Lactobacillus GG (LGG) is an effective adjunct to lactulose for treating constipation in children. Study design: Eighty- four chi ldren (2- 16 years of age) with constipation (< 3 spontaneous bowel movements [ BMs] per week for at least 12 weeks) were enrolled in a double- blind, randomiz ed placebo- controlled trial in which they received 1 mL/kg/day of 70% lactul ose plus 109 colony- forming units (CFU) of LGG (experimental group, n = 43) or a placebo (control group, n = 41) orally twice daily for 12 weeks. The primary outcome measure was treatment success, and analyses were performed on an intenti on- to- treat basis. Results: Treatment success, defined as ≥ 3 spontaneous B Ms per week with no fecal soiling, was similar in the control and experimental g roups at 12 weeks (28/41 [68% ] vs 31/43 [72% ], respectively; P =. 7) and at 24 weeks (27/41 [65% ] vs 27/42 [64% ], respectively; P = 1.0]. Groups also di d not differ in their mean number of spontaneous BMs per week or episodes of fec al soiling per week at 4, 8, and 12 weeks. Adverse events and overall tolerance did not differ between groups. Conclusion: LGG, as dosed in this study, was not an effective adjunct to lactulose in treating constipation in children.

先天性支气管狭窄手术治疗的预测因子:一项多中心文献分析

Background: Congenital tracheal stenosis (CTS) often requires urgent surgical intervention. We evaluated prognostic factors to determine the risks of surgical interventions by conducting a retrospective review of recent case series. Methods: Cases of CTS between 2002 and 2004 from our institution and recently published series that provided primary data on the demographics, complications, and outcomes of patients with CTS were analyzed. Univariate, model fit, and multivariate logistic regression analyses were performed using the SAS Statistical Program. Results: There were 68 patients who were treated (cartilage patch tracheoplasty, n = 31; slide tracheoplasty, n = 37), with 19 deaths (overall mortality = 28%). A total of 10 patients who underwent cartilage patch tracheoplasty died (32%mortality), whereas only 9 patients died following slide tracheoplasty (24%mortality). A total of 8 of 11 patients who were repaired at the age of 1 month or younger died (73%mortality), whereas only 11 of 57 patients who were repaired at an age older than 1 month died (19%mortality) (P = .04). A total of 10 of 19 patients with CTS who had comorbid intracardiac anomalies died following CTS repair (53%mortality), whereas only 9 of 49 patients with CTS who did not have intracardiac anomalies died (18%mortality) (P = .02). Conclusions: This is the first report on the prognostic factors determining surgical outcomes for CTS. The highest mortality rate was observed in CTS patients younger than 1 month and in those with intracardiac anomalies. Congenital tracheal stenosis repairs in these patient subgroups should be considered with caution.

出生前反复暴露于皮质激素的新生儿的呼吸窘迫综合征:一项随机化对照试验

Background: The efficacy and safety of repeat doses ofprenatal corticosteroids remains uncertain. Our aim was to establish whether repeat prenatal corticosteroids given to women at risk of preterm birth can reduce neonatal morbidity without harm. Methods: In this hospital-basedstudy, 982 women who remained at risk of preterm birth at less than 32 weeks’ gestation, 7 or more days after receiving a first course of prenatal corticosteroids,were randomly assigned to receive a repeat intramuscular dose of either 11.4 mg betamethasone (as Celestone Chronodose), or saline placebo. This was repeated every week the woman remained undelivered, at less than 32 weeks’ gestation, and at risk of preterm birth. Primary outcomes were occurrence and severity of neonatal respiratory distress syndrome, use and duration of oxygen and mechanical ventilation, and weight, length, and head circumference at birth and hospital discharge. Statistical analyses were on an intention to treat basis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN48656428. Findings:Fewer babies exposed to repeat corticosteroids had respiratory distress syndrome (33%vs 41%; relative risk 0.82,95%CI 0.71-0.95, P=0.01) and fewer had severe lung disease(12%vs 20%; relative risk 0.60, 95%CI 0.46-0.79,P=0.0003) than those in the placebo group. In keeping with these benefits, babies exposed to repeat corticosteroids needed less oxygen therapy (P=0.03), and shorter duration of mechanical ventilation (P=0.01). Mean weight,length, and head circumference at birth and hospital discharge did not differ between treatment groups. Z-scores for weight (P=0.04) and head circumference (P=0.03) at birth were lower in the babies who received repeat corticosteroids although at the time of hospital discharge Z-scores did not differ between treatment groups (P=0.29 for weight, P=0.48 for head circumference). Interpretation:Exposure to repeat doses of antenatal corticosteroids reduces neonatal morbidity. Pending long-term outcome results, the short-term benefits for the babies in our study support the use of repeat doses of corticosteroids in women who remain at risk of very preterm birth 7 or more days after an initial course.

三维CT门静脉成像评价肝外门静脉高压患儿的肝外门静脉形态:一种新的肝外门脉高压病因理论

Background/Purpose:The cause of extrahepatic portal hypertension in children has not been clarified. Our aim was to determine the morphological features of the extrahepatic portal vein in children with extrahepatic portal hypertension by 3-dimensional computed tomographic portography and to clarify the etiology of this disorder. Materials and Methods:Six patients ranging in age from 10 to 18 years (median age,12.8 years) who had portal hypertension presented with hematemesis. They underwent intravenous computed tomographic portography using a helical computed tomography scanner and 3-dimensional image reconstruction. Results:The extrahepatic portal vein was visualized in all patients by 3-dimensional computed tomographic portography. None of the patients showed extrahepatic portal vein obstruction or cavernous transformation. All patients had a tortuous η -shaped extrahepatic portal vein,and a line could be drawn through the flexures of the portal vein to the hepatic hilum. Conclusion:In children,extrahepatic portal hypertension is not caused by extrahepatic portal vein obstruction and may be of embryological origin.

L-5-羟色氨酸(L-5-HTP)治疗儿童夜惊

为了证实关于使用L-5-HTP对夜惊有一定的疗效的假说,我们对一组夜惊儿童进行了一个开放性药理学试验,并且与一组患此病但没有接受L-5-HTP 治疗的儿童进行了对照。据罗马大学发育神经病学和精神病学部门的睡眠中心提供,该试验一共有45例受夜惊影响儿童参与(34例男性,11例女性,年龄3.2- 10.6岁)。

新生儿重症监护病房中氟康唑预防性给药对侵袭性念珠菌病发病和预后的影响

Objectives: We assessed the impact of intravenous fluconazole prophylaxis (FP) in extremely low birthweight (ELBW[<1000 g]) infants on the incidence of and ou tcome from invasive candidiasis (IC) in all infants admitted to a neonatal inten sive care unit (NICU). Study design: Beginning April 1, 2002, FP was given to EL BW infants aged < 5 days admitted to the NICU of Woman’s Hospital of Texas. Inf ants in NICU in whom IC developed during the first 2 years of FP (FP period) wer e compared with those with IC during 2000-2001. Results: During 2000-2001 and the FP period, the incidence of IC in ELBW infants decreased from 7%(15 of 206) to 2%(5 of 240) (P = .01), and the IC-related mortality rate decreased from 1 2%(4 of 33) to 0 (0 of 40) (P = .04); the incidence of IC increased from 0.1%( 4 of 2806) to 0.2%(8 of 3372) in infants of birth weight ≥1000 g (P = .06), an d no IC-related deaths occurred. During the FP period, IC developed in older in fants (24 vs 12 days; P = .12) who had similar risk factors for IC. Conclusion: Invasive candidiasis occurred in our NICU in spite of FP and shifted to bigger,m ore mature infants who had a better outcome.

周围湿度对极早产儿皮肤屏障成熟度的影响

Objectives:To test the hypothesis that the level of relative humidity (RH) in which preterm infants are nursed might in-fluence their postnatal skin maturation. Study design:In 22 preterm infants (GA 23-27 weeks),transepidermal water loss(TEWL) was determined at postnatal ages (PNA) of 0,3,7,14,and 28 days. At a PNA of 7 days,the infants were randomized to care at either 50%or 75%RH. Results:TEWL decreased at a slower rate in infants nursed at the higher RH. At a PNA of 28 days,TEWL was about twice as high in infants nursed at 75%RH (22 ±2 g/m2 h) than in those nursed at 50%RH(13 ±1 g/m2 h; P < 0.001). Conclusions:The results indicate that the level of RH influences skin barrier development,with more rapid barrier formation in infants nursed at a lower RH.The findings have an impact on strategies for promoting skinbarrier integrity in extremely preterm infants.

完全性结肠无神经节细胞症的长期转归:32年回顾

Background/Methods: A 32- year retrospective review from 1972 to 2004 analyzed complications and long-term outcomes in children with total colonic aganglionosis (TCA) as they relate to the procedure performed. Results: Thirty-six patients (27 boys, 9 girls) had TCA. The level of aganglionosis was distal ileum (26), mid-small bowel (8), midjejunum (1), and entire bowel (1). Enterostomy was performed in 35 of 36. Eight developed short bowel syndrome. Twenty-nine (81% )- had a pull-through at 15± 6 months (modified Duhamel 20, Martin long Duha-mel 4, and Soave 5). Six had a Kimura patch. Postoperative complications (including enterocolitis)- were more common after long Duhamel and Soave procedures. Seven (19% ; 2 with Down’s syndrome) died (3 early, 4 late)- from pulmonary emboli (1), sepsis (1), fluid overload (1), viral illness (1), liver failure (1), arrhythmia (1), and total bowel aganglionosis (1). Mean follow-up was 11± 9 years (range, 6 months- 29 years). Twenty-four (83% ) of 29 patients exhibited growth by weight of 25% or more, 21 (91% ) of 23 older than toddler age had 4 to 6 bowel movements per day, and 17 (81% )- of 21 were continent. In 5 of 6, the Kimura patch provided functional benefit with proximal disease. Conclusion: Longterm survival was 81% . The highest morbidity occurred with long Duhamel or Soave procedures. The modified Duhamel is our procedure of choice in TCA. Bowel transplantation is an option for TCA with unadapted short bowel syndrome.

中国低出生体重儿发育状况研究:16年纵向调查

Aim: To compare the growth and neurodevelopment of low birthweight (LBW) and n ormal-birthweight (control) infants born and raised in China. Design: Prospecti ve cohort study. Subjects and setting: 203 LBW (1200-2499 g) and 71 control (≥ 2500 g) infants born at two Shanghai hospitals in 1983 did not differ for date o f birth, gender, parental occupation, parental weight and age. LBW < 10th centil e at ≥37 wk gestation was defined as small for gestational age (SGA, n = 102). LBW at < 37 wk gestation was defined as preterm (n = 101). Main outcome measures : Weight, height, head circumference, Gesell developmental quotient (DQ), Wechsl er intelligence quotient (IQ), and scholastic achievement score. Results: Of the 274 enrolled subjects, 234 (85%) returned at 6 mo, 135 (49%) at 6 y, and 104 (38%) at 16 y. SGA, preterm, and control subjects did not differ in rates of fo llow-up or baseline characteristics. However, SGA and preterm were lower than c ontrol subjects in weight and head circumference through 16 y, height through 4 y, DQ through 3 y, IQ at 5 and 16 y, and scholastic achievement at 16 y. Catch-up to growth in the control group, defined as > 3rd centile, and normal IQ, defi ned as ≥85, were both more common among preterm than SGA subjects. Conclusions: Adolescents in China with birthweights of 1200-2499 g, and particularly those who were SGA, lag behind peers with birthweights > 2500 g in physical growth, co gnitive capacity, and school achievement. The findings suggest that LBW adolesce nts in China today represent a population in need of evaluation and support.

儿童和青少年PHOX2B型先天性中枢性低通气综合征患者的面部表型:面部畸形的定量研究

Congenital central hypoventilation syndrome (CCHS) is caused by mutations in PHOX2B,which is essential for maturation of the neural crest into the autonomic nervous system and is expressed in the dorsal rhombencephalon,a region that gives rise to facial structures. Digital photographs of 45 individuals with PHOX2B-confirmed CCHS,and 45 matched controls were analyzed for 17 linear and 6 angular measurements,and 9 derived indices. Paired t tests were used to compare group means,correlation was calculated between PHOX2B polyalanine expansion number and facial measures,and stepwise logistic regression was used to predict case-control and genotype status. CCHS cases differed significantly from controls on 13 variables (6 after p value correction:nasolabial angle,upper lip height,lateral lip height,facial index,upper facial index,and presence of inferior inflection of the lateral segment of the upper lip vermillion border). Five variables were able to predict correctly 85.7%of CCHS cases and 82.2%of controls:upper lip height,binocular width,upper facial height,nasal tip protrusion,and inferior inflection of the upper lip vermillion border. A negative relationship between number of repeats and four anthropometric measures was observed:mandible breadth,nasolabial angle,lateral lip height,and mandible-face width index. These results suggest a characteristic facial phenotype in children and young adults with CCHS,due to an expansion mutation in PHOX2B.