肺炎支原体肺炎患儿肺炎支原体耐药性与DNA载量和基因型的关系研究

目的探讨肺炎支原体(MP)肺炎患儿MP耐药情况及其与DNA载量和基因型的关系。方法选取2012年1月至2016年12月诊断为MP肺炎的230例住院患儿为研究对象,采集所有患儿咽拭子标本,采用快速培养基培养药敏法测定9种常用抗菌药物对MP临床分离株的药物敏感性;荧光实时定量PCR检测患儿咽拭子MP-DNA载量;PCR测序检测MP 23S r RNA V区2063位基因型。结果 230例MP患儿中,86例2063位基因型为A(37.4%),134例为G(58.3%),8例为C(3.5%),2例为T(0.9%)。突变基因型(G+C+T)MP-DNA载量高于野生基因型(A)菌株(P0.05);红霉素、阿奇霉素、克拉霉素、克林霉素耐药组MP-DNA载量高于非耐药组(P0.05)。MP对大环内酯类抗生素耐药率较高,60%以上产生大环内酯类耐药的病例均检测出A2063G突变,喹诺酮类药物少见MP耐药(低于2%)。结论 23S r RNA V区2063位点发生基因突变可能导致MP对大环内酯类药物耐药和DNA载量的变化,可作为MP治疗用药的选择依据。     

Comparison of chloroquine with artesunate in the treatment of cerebral malaria in Ghanaian children.

Despite previously reported chloroquine-resistant forms of PF falciparum in Ghana, chloroquine remains the drug of choice in severe malaria. Artemisinin derivatives have been shown to be effective against chloroquine-resistant strains in other endemic areas. This open randomized study was conducted to compare the efficacy of chloroquine and artesunate in the treatment of childhood cerebral malaria. Out of 82 subjects that fulfilled the inclusion criteria, 36 were randomized to receive chloroquine and 46 to receive artemisinin. Blantyre coma scores, temperature and parasitaemia were monitored. Mortality and neurological deficits were documented. There was no difference in mortality rates (chloroquine, 16.7 per cent; artesunate, 21.7 per cent; p = 0.6), neurological deficit at day 14 (chloroquine, 0 per cent; artesunate, 4.3 per cent; p = 0.3), resolution of fever (p = 0.55), and coma recovery time (p = 0.8), between the two groups. The results suggest that syrup chloroquine and intramuscular/oral artesunate currently give comparable clinical responses in the treatment of cerebral malaria in Ghana. Possible reasons for this are discussed, and suggestions are made for future antimalarial drug policy.     

Impact of age and drug resistance on mortality in typhoid fever.

The risk factors for mortality were analysed in a consecutive group of 1158 children presenting to the Aga Khan University Medical Center, Karachi, with multidrug resistant typhoid fever that had been proved on culture. There were 19 deaths, representing an overall case fatality rate of 1.6%. Multidrug resistant typhoid was associated with a more severe clinical illness and higher rates of toxicity, hepatomegaly, hypotensive shock, and death. Irrespective of drug resistance status, typhoid fever was found to be a more severe illness in young infants with significantly higher rates of diarrhoea, hypotensive shock, and mortality. Univariate analysis of admission characteristics associated with increased risk for mortality revealed significant association with younger age (p < 0.05), hypotensive shock or hypothermia (p < 0.001), obtundation (p < 0.001), seizures (p < 0.05), anaemia at admission (p < 0.005), and leucocytosis (p < 0.001). Logistic regression analysis of risk factors for mortality showed persistent association of hypothermia, toxicity, and anaemia with mortality. The data provides evidence that multidrug resistant typhoid in childhood is associated with increased risk of mortality, especially in infancy and closer attention to several risk factors for increased morbidity and case fatality rates may lead to improved outcome of treatment.     

Impact of age and drug resistance on mortality in typhoid fever

The risk factors for mortality were analysed in a consecutive group of 1158 children presenting to the Aga Khan University Medical Center, Karachi, with multidrug resistant typhoid fever that had been proved on culture. There were 19 deaths, representing an overall case fatality rate of 1.6%. Multidrug resistant typhoid was associated with a more severe clinical illness and higher rates of toxicity, hepatomegaly, hypotensive shock, and death. Irrespective of drug resistance status, typhoid fever was found to be a more severe illness in young infants with significantly higher rates of diarrhoea, hypotensive shock, and mortality. Univariate analysis of admission characteristics associated with increased risk for mortality revealed significant association with younger age (p < 0.05), hypotensive shock or hypothermia (p < 0.001), obtundation (p < 0.001), seizures (p < 0.05), anaemia at admission (p < 0.005), and leucocytosis (p < 0.001). Logistic regression analysis of risk factors for mortality showed persistent association of hypothermia, toxicity, and anaemia with mortality. The data provides evidence that multidrug resistant typhoid in childhood is associated with increased risk of mortality, especially in infancy and closer attention to several risk factors for increased morbidity and case fatality rates may lead to improved outcome of treatment.     

Anemia of persistent malarial parasitemia in Nigerian children.

One hundred children aged 0-60 months, 63 males and 47 females, were studied prospectively over a period of 9 months to determine the effect of persistent malaria parasitemia on their packed cell volume (PCV) levels. Thick and thin blood films for parasite identification and counts were done. Patients were randomly assigned to two treatment groups: 62 patients received chloroquine, while 38 patients received fansidar. Mean parasite count (2789.2+/-1809.6) and mean temperature (36.83 (0.66 degrees C) in the fansidar group at day 7 were found to be significantly lower than at enrollment (p < 0.05). This also corresponded with significantly higher mean PCV values of 33.85+/-4.72 (p < 0.05). In the chloroquine group it was only by day 21 that a significant reduction in parasite count and associated increase in PCV levels were noted. A negative correlation between mean parasite counts and PCV levels was observed (r = -0.9512). The hematological recovery time for chloroquine was longer at 21 days compared to fansidar which was 7 days. RII level of parasite resistance was found in 81 patients, 32 in the fansidar group, and 49 in the chloroquine group. The level of resistance to the used first-line antimalarials was found to be rather high in Enugu, south-east Nigeria. This calls for more extensive community-based studies and probable changes in drug policies.     

Mutational analysis of the RET and GDNF gene in children with hypoganglionosis.

Germline mutations of the RET (10q11.2) have been reported in Hirschsprung's disease (HSCR) at a rate of 15-45%. Recently, the glial cell line-derived neurotrophic factor (GDNF) was identified as one of the ligands of the RET, and GDNF (5p12-p13.1) mutations were also found in association with RET mutations in HSCR patients. We analysed the DNA sequence of RET and the GDNF of patients with hypoganglionosis. We investigated the germline mutation in 5 patients histologically diagnosed with hypoganglionosis. DNAs were extracted from peripheral blood lymphocytes of these patients. The PCR primers were designed for RET tyrosine kinase domain (exon 13-17) and GDNF (exon 1-2). The DNA sequence was determined using a direct DyeDeoxy Terminator Cycle method. The analysis of RET showed silent mutation at the codon 769 (CTT-->CTG) by DNA polymorphism in all patients. No other mutation of the RET or GDNF was evident. These results suggest that the RET or GDNF may not contribute to the pathogenesis of hypoganglionosis, which is suspected to be genetically different from HSCR.     

The effect of mannose-binding protein gene polymorphisms in recurrent respiratory system infections in children and lung tuberculosis

Mannose-binding lectin (MBL) is able to bind pathogens as an opsonin and plays an important role in the innate immunity. The aim of the present study was to determine the frequencies of the MBL gene variants in the Turkish population and to examine the presence of any association between MBL variants and development of tuberculosis (TB) in adults and recurrent respiratory tract infections in children. Two structural gene mutations in exon 1 of MBL gene (codon 54 and codon 57) were studied. The overall distribution of genotypes did not significantly differ between controls and TB patients/children with recurrent respiratory system infections. The frequency of allele B was calculated as 0.14, 0.09 and 0.06 for control, TB patients and children with recurrent respiratory system infections, respectively. It was found to be significantly lower in children with recurrent respiratory system infections than in controls (chi2: 4.68, d.f: 1, p: 0.030).     

Comparative trial of short-course ofloxacin for uncomplicated typhoid fever in Vietnamese children

An open, randomised comparison of 2 or 3 days of oral ofloxacin (10 mg/kg/day) for uncomplicated typhoid fever was conducted in 235 Vietnamese children. Multi-drug-resistant Salmonella typhi was isolated from 182/202 (90%) children and 5/166 (3%) tested isolates were nalidixic acid-resistant (Na(R)). Eighty-nine of 116 children randomised to 2 days and 107/119 randomised to 3 days were blood culture-positive and eligible for analysis. There were 12 (13.5%) failures in the 2-day group (six clinical failures, four blood culture-positive post treatment, two relapses) compared with eight (7.5%) failures in the 3-day group (four clinical failures, one blood culture-positive post treatment, three relapses) (OR 1.9, 95% CI 0.7-5.5,p = 0.17). There were no significant differences in the mean (95% confidence interval) fever clearance times (h) [92 (82-102) vs 101 (93-110), p = 0.18] or duration of hospitalisation (d) [7.6 (7.2-8.1) vs 8.0 (7.6-8.4), p = 0.19] between the two groups. There was one failure in the four eligible children infected with an Na(R) isolate of S. typhi. No adverse events were attributable to the ofloxacin. These results extend previous observations on the efficacy of short courses of ofloxacin for children with uncomplicated multi-drug-resistant typhoid fever.     

Cefaclor versus penicillin V in staphylococcal infections in children

Although rheumatic fever virtually no longer occurs in France, pharyngitis due to group A beta-hemolytic streptococci (ABHS) remains a common pediatric problem. American studies have underscored the high rate of bacteriologic treatment failures and recurrences of ABHS pharyngitis. Furthermore, several comparative studies have demonstrated that cephalosporins provide better results on these two parameters. This prospective randomized study compared the effectiveness of penicillin V (50,000 to 100,000 IU/kg/day in three divided doses) and Cefaclor (20 to 40 mg/kg/day in three divided doses), each given for ten consecutive days. From September 1989 through October 1990, 117 children (mean age 5.7 years) were entered into the study. All study subjects were seen as outpatients and found to have ABHS pharyngitis on the basis of a rapid screening test and confirmatory bacteriologic studies. Cefaclor was given to 56 patients and penicillin V to 61. Reevaluation with a repeat bacteriologic study was performed in all patients at the end of the treatment period, or earlier in the event of new clinical manifestations, and towards D40. Among patients given penicillin V, bacteriologic failure rate at completion of therapy was 19.6%, clinical failure rate on D10 was 8%, and recurrence rate on D40 was 16.5%. Cefaclor exhibited greater bacteriologic and clinical effectiveness, with 3.4% bacteriologic failures on D10 (p less than 0.01), 1.7% clinical failures on D10, 8.9% clinical recurrences between D10 and D40, and an overall 10.6% rate of failure or recurrence (p = 0.05).     

P53 gene mutations in pleuropulmonary blastomas

Pleuropulmonary blastoma (PPB) is rarechildhoodtumororiginating fromeitherlung orpleura. Although several cytogenetic changes, such as trisomy 2, trisomy 8, and loss of 17p material, have been reported, evidence of gene mutations is still lacking. Pathologically, PPB shares similarities with rhabdomyosarcoma in which p53 mutations are frequently detected. Possible implication of p53 mutations in PPB was investigated. PPBs of 3 patients were analyzed for occurrence of p53 mutations by using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) method, and the nature of mutations was confirmed by direct sequencing. Two PPBs were confirmed to harbor p53 mutations. One was a Val to Leu substitution at codon 173, and another was a ArgArg to TrpCys substitution at codons 282 and 283. In each tumor, only the mutated allele was detected, suggesting inactivation of p53. Both patients with mutations had fatal outcome, while the remaining patient in whom no mutation was detected is disease free for 3 years after completion of treatment. The results raise the possibility that p53 inactivation can occur as a nonrandom genetic change involving the pathogenesis and outcome of PPB. Further studies in a larger series are necessary to clarify these matters.     

儿童感染幽门螺杆菌对克拉霉素耐药情况及耐药机制初步研究

目的了解儿童幽门螺杆菌(Helicobacter pylor,Hp)对克拉霉素的耐药情况,探讨Hp对克拉霉素耐药性与23S rRNA基因突变的关系。方法。108例胃黏膜标本均取自2002年10月-2004年1月在浙江大学医学院附属儿童医院进行胃镜检查的患儿,经分离培养鉴定为Hp菌株后,分别采用E-test法和琼脂稀释法检测克拉霉素的最低抑菌浓度(minimum inhibitory concentration,MIC),确定Hp菌株对克拉霉素的耐药性。提取所有108株Hp基因组DNA进行PCR扩增,用限制性片段长度多态性(restriction fragment length polymorphism,RFLP)检测克拉霉素耐药菌株的点突变。结果Hp菌株对克拉霉素耐药率为14．8％(16／108)。16株耐药菌株23S rRNA V功能区PCR扩增片段RFLP分析,13株被BsaⅠ酶切,提示2144位点存在A→G点突变,3株被BbsⅠ酶切,提示2143位点存在A→G点突变,所有敏感菌株均不能被BsaⅠ和BbsⅠ酶切,提示无23S rRNA基因相应位点的点突变。同时本研究中并未发现突变形式与耐药程度的相关性。结论儿童Hp感染对克拉霉素耐药率较高;23S rRNA基因点突变是Hp对克拉霉素耐药的重要因素。耐药菌株存在A2144G和A2143G突变,以前者为主。     

p53 gene mutations in pediatric brain tumors

We investigated the frequency of p53 mutations in 47 pediatric brain tumors of various histologic subtypes that were collected over a period of 5 years. The specimens included 15 primitive neuroectodermal tumors (PNETs), 17 low grade astrocytomas, one anaplastic astrocytoma, three glioblastomas (GBMs), one mixed glial tumor, eight ependymomas, one choroid plexus carcinoma, and one gangliocytoma/ganglioneuroma. Mutations were identified by single strand conformation polymorphism analysis of exons 4–8 and verified by sequencing. Mutations were present in 2 of 3 cases of GBM, but not in 17 low grade astrocytomas (P = 0.02, Fisher's exact test). One GBM demonstrated a germline GGC to AGC transition (gly to ser) at codon 245 with loss of the wild-type allele. A second GBM contained a CGG to TGG transition (arg to trp) at codon 248, also with loss of the wildtype allele, but normal tissue was not available for comparison. In addition, one of 15 PNETs retained heterozygosity but demonstrated a somatic CGT to TGT transition (arg to cys) at codon 273. p53 mutations were absent in other histologic subtypes and in two cases with multiple primary cancers. These data are consistent with earlier findings that p53 mutations are rare in PNETs, which are primarily pediatric tumors. In contrast to adult gliomas, p53 mutations in pediatric gliomas appear restricted to the GBMs. The lack of p53 mutations in pediatric low grade astrocytomas suggests not only histological differences, but also a different molecular pathogenesis in adult and pediatric patients. © 1995 Wiley-Liss, Inc.     

Analysis of N-ras gene mutations in medulloblastomas by polymerase chain reaction and oligonucleotide probes in formalin-fixed, paraffin-embedded tissues

Precise data on the incidence of transforming ras oncogenes in pediatric tumors and the correlations with the histopathological properties of the tumors are very limited. Additionally the presence of ras activation in medulloblastomas has not been investigated so far. Using a combination of techniques including in vitro gene amplification by polymerase chain reaction (PCR) and detection of single base mutations by sequence-specific oligonucleotides we studied N-ras activation (mutations at codon 12, 13, and 61) in 32 medulloblastomas. DNA was isolated from 20 microns sections of formalin-fixed paraffin-embedded tissue. Mutations were found in 3 out of 32 examined medulloblastomas. In all cases only mutations of codon 61 were found: two of three mutations were C to A mutations at position 1 of the codon 61 (leading to a substitution of a glutamine residue for a lysine) and one was A to T mutation at position 3 in the same codon (glutamine-histidine). Our results indicate 10% incidence N-ras mutation in medulloblastoma, higher than in other CNS tumors studied so far. The main advantages of the procedure described are its greatly improved sensitivity, the increased speed with which tumor samples can be analyzed, and the possibility of using paraffin-embedded sections to analyze various rare tumors in retrospect.     

A randomized and comparative study of intravenous immunoglobulin and mega dose methylprednisolone treatments in children with acute idiopathic thrombocytopenic purpura

The most common cause of mortality in childhood acute idiopathic thrombocytopenic purpura (ITP) is intracranial hemorrhage (ICH), which occurs in about 0.1% of children with platelet counts below 20,000/microl. Forty-two children (1-13 years) with ITP and platelet counts < or = 20,000/microl were randomly divided into two groups. Twenty patients received mega-dose methylprednisolone (MDMP) in a dosage of 30 mg/kg/d for three days and 20 mg/kg/d for four days. Twenty-two patients received intravenous immunoglobulin (IVIG) in a dosage of 1 g/kg/d two days. Platelet counts of the patients were determined at diagnosis, at 2, 4, 7, 14, 30, 60, 90, 120, 150, and 180 days and at three-month intervals after the 6th month. The mean platelet counts of both groups gradually increased and peaked on the 7th day (p > 0.05). There were no significant differences between the mean platelet counts of patients, in the two groups on treatment days 0, 2, 4, 7, and 14. The mean time for achievement of platelet counts above 20,000/microg in the MDMP group and the IVIG group was 4.1 and 2.9 days (p < 0.05) and above 50,000/microl was 5.0 and 5.2 days (p > 0.05), respectively. The percentages of patients with platelet counts above 20,000/microl at the 2nd day of the treatment were 50% in the MDMP group, and 86% in the IVIG group (p < 0.05). No significant differences were observed in the mean platelet counts of the two groups treatment days 30, 60, 90, 120 and 180 (p > 0.05). Chronic ITP developed in five patients (25%) in the MDMP group, and in four patients (18%) in the IVIG group (p > 0.05). Intravenous immunoglobulin (IVIG) (1 g/kg/d for 2 days) and MDMP treatments (30 mg/kg/d for 3 days, 20 mg/kg/d for 4 days, perorally) are equally effective in the treatment of acute ITP. Because of its nonbiologic source, lower cost, fewer side effects and oral use, we prefer oral preparations of MDMP in the treatment of childhood ITP.     

Clinical efficacy of four schemes for vivax malaria treatment in children

OBJECTIVES: In the treatment of vivax malaria, an important factor affecting the occurrence of relapse is the duration of treatment. In Belém, a number of patients with vivax malaria were found to be cured despite failure to complete the standard course of treatment. In Belém, a number of patients with vivax malaria were found to be cured despite failure to complete the standard course of treatment. This observation suggested the present study, investigating more practicable courses of treatment for children with vivax malaria.METHODS: A randomized prospective clinical trial was conducted in 200 outpatient children with vivax malaria. Parasite clearance time and response to four therapeutic schedules were investigated: a) chloroquine*, 10 mg/kg in a single dose (chloroquine SD) + primaquine, 0.50 mg/kg/dose for 7 days; b) chloroquine SD + primaquine, 0.25 mg/kg/dose for 7 days; c) chloroquine SD + primaquine, 0.50 mg/kg/dose for 5 days; d) chloroquine SD + primaquine, 0.25 mg/kg/dose for 5 days. Fisher?s Exact test was used to compare the responses to the schedules.RESULTS: All 144 children who completed the study had clearance of asexual parasitemia by the fourth day of treatment. Significant differences were observed between schedules A/D (p= 0.022) and C/D (p= 0.005). A doubled dose of primaquine (schedules A and C) proved to be significantly more effective (p=0.0042) than the standard dose (B and D). However, duration of treatment had no significant effect (p = 0.6104).CONCLUSIONS: In this study, complete cure of vivax malaria was better achieved with a doubled dose of primaquine than with standard doses. Effectiveness of the doubled dose was independent of the duration of treatment. Treatment schedule D is not recommended.     

Macrolide resistance among middle ear isolates of Streptococcus pneumoniae observed at eight United States pediatric centers: prevalence of M and MLSB phenotypes

BACKGROUND: Increasing macrolide resistance among middle ear isolates complicates treatment of otitis media in children. When macrolide resistance is mediated via an efflux pump (M phenotype), the MICs of erythromycin, clarithromycin and azithromycin are usually below 32 microg/ml, and the pneumococcus remains susceptible to clindamycin. The association of prior specific macrolide therapy with the isolation of a macrolide resistant strain has not been reported. OBJECTIVES: To determine the mechanism of macrolide resistance in Streptococcus pneumoniae recovered from the middle ears of children with otitis media and their association, if any, with ethnicity, age, serogroup/serotype and prior antibiotic therapy. METHODS: Middle ear isolates collected by members of the United States Pediatric Multicenter Pneumococcal Surveillance Group during a 6-year period from September 1994 through August 2000 were studied. Antibiotic susceptibility to penicillin and ceftriaxone was determined by microbroth dilution. Disc diffusion susceptibility to erythromycin and clindamycin was performed to categorize macrolide resistance mechanisms. The medical record was reviewed to determine demographics and history of previous antibiotic therapy. Isolates were serogrouped or serotyped by the capsular swelling method. RESULTS: Of the 1088 isolates available for testing, 51% were nonsusceptible to penicillin and 37% were nonsusceptible to erythromycin. Erythromycin resistance increased form 15% in 1994 through 1995 to 56% in 1999 through 2000. Seventy-five percent of macrolide-resistant strains were M phenotype. Macrolide resistance was less likely in isolates recovered from African-Americans and more likely in isolates obtained from children <3 years of age and from isolates obtained at time of tympanostomy tube placement. Neither erythromycin, nor clarithromycin nor azithromycin prescribed in the 30 days before infection was more likely than another to be associated with increased macrolide resistance. However, any macrolide alone or in combination with another antimicrobial taken before infection was associated with increased macrolide resistance among the S. pneumoniae organisms isolated from the middle ear. CONCLUSIONS: Macrolide resistance among middle ear isolates of S. pneumoniae increased during the 6-year study. The proportion of M phenotype remained constant at 75%, meaning that these isolates remain susceptible to clindamycin. Continued surveillance to document potential changes is essential.     

Group B streptococcal colonization of pregnant women and their neonates. Epidemiological study and controlled trial of prophylactic treatment of the newborn.

Colonization with group B streptococci of the genital tract was studied in 1 115 women during the last trimester of pregnancy. 76 or 6.82% were found to harbour this bacterium. The incidence of contamination was significantly higher among Belgian women than among parturients of Mediterranean origin (p less than 0.001). It was also more frequent in primigravidae (p less than 0.05) and in the poorer (0.10 less than p greater than 0.05). At the time of admission in the delivery room, it was noticed that rupture of the amniotic membranes for more than 24 hours was more often associated with group B streptococcal carriage by the mother (p less than 0.001). 29 out of 68 (42.6%) infants born to group B streptococci positive mothers were colonized at birth. 67 of them were submitted to a controlled trial of immediate versus delayed penicillin therapy. 44.8% and 42.1% of the neonates were contaminated at birth in each group of treatment respectively. No instance of group B streptococcal infection developed in either group. This suggests that immediate therapy with penicillin of infants of group B streptococci positive mothers has no definite advantage upon delayed treatment.     

The effect of transfusion on lung capacity, diffusing capacity, and arterial oxygen saturation in patients with thalassemia major

Our previous cross-sectional study of patients with thalassemia major suggested progressive lung changes characterized by low total lung capacity, hypoxemia, and elevated transfer factor for carbon monoxide. We reevaluated nine of the patients for three reasons: to determine the relationship of the previous findings to the immediate effects of blood transfusion; to assess the longitudinal progression of the lung changes; and to evaluate the effect of splenectomy on lung volume changes in these patients, all of whom underwent splenectomy in the interval between the two studies. We found that during the 5- to 6-yr period between studies total lung capacity had decreased significantly (p less than 0.05) from a mean 86% predicted to a mean 79% predicted. However, vital capacity increased significantly (p less than 0.05) from a mean 81% predicted to 88% with no significant change in functional residual capacity. There was no significant immediate effect of transfusion on total lung capacity, vital capacity, or functional residual capacity. However, the diffusion constant for carbon monoxide increased significantly (p less than 0.005) immediately following transfusion and there was a positive correlation between the increase and the amount of blood transfused (r = 0.74, p less than 0.05). Arterial oxygen saturation was below 95% in five of eight patients and increased significantly with transfusion (p less than 0.05). We conclude: 1) thalassemia major and/or its treatment is associated with hypoxemia and a progressive reduction in total lung capacity. 2) Despite the progressive reduction in total lung capacity, splenectomy in patients with thalassemia major increases expiratory reserve volume and thereby increases vital capacity.     

儿童EBV阳性噬血细胞综合征的遗传分析及其与Th1/Th2细胞因子的关系

目的 探讨遗传变异对EBV阳性噬血细胞综合征（HLH）患儿预后的影响及其与细胞因子的关系。方法 选取81例EBV阳性且已进行相关基因测序的HLH患儿，根据有无基因突变分为无突变组（n=35）和突变组（n=46），再根据基因突变方式分为单杂合突变（SHM）亚组、双杂合突变（DHM）亚组和纯合或复合杂合突变（H-CHM）亚组。测定各组患儿血清细胞因子水平，分析其与HLH基因突变的关系。结果 UNC13D基因突变出现频率最高（13/46，28%）。STXBP2 c.575G > A （p.R192H）和UNC13D c.604C > A （p.L202M）基因突变首次被报道，均判定为“可能致病的”。突变组TNF-α水平高于无突变组，IFN-γ水平低于无突变组（P < 0.05）。DHM亚组IL-4水平高于无突变组，H-CHM亚组IL-4水平低于DHM组（P < 0.0083）。H-CHM亚组的1年总生存率（39%±15%）低于无突变组、SHM亚组和DHM亚组（分别为85%±6%、86%±7%和91%±9%，P=0.001）。结论 具有基因突变的HLH患儿IFN-γ水平显著降低；H-CHM患儿的预后较差，而其他突变对其预后影响不显著，这可能有助于医生进行临床决策。     

GROUP B STREPTOCOCCAL COLONIZATION OF PREGNANT WOMEN AND THEIR NEONATES Epidemiological Study and Controlled Trial of Prophylactic Treatment of the Newborn

Abstract. Colonization with group B streptococci of the genital tract was studied in 1115 women during the last trimester of pregnancy. 76 or 6.82 % were found to harbour this bacterium. The incidence of contamination was significantly higher among Belgian women than among parturients of Mediterranean origin ( p < 0.001). It was also more frequent in primigravidae ( p <0.05) and in the poorer (0.10 < p > 0.05). At the time of admission in the delivery room, it was noticed that rupture of the amniotic membranes for more than 24 hours was more often associated with group B streptococcal carriage by the mother ( p <0.001). 29 out of 68 (42.6%) infants born to group B streptococci positive mothers were colonized at birth. 67 of them were submitted to a controlled trial of immediate versus delayed penicillin therapy. 44.8 % and 42.1 % of the neonates were contaminated at birth in each group of treatment respectively. No instance of group B streptococcal infection developed in either group. This suggests that immediate therapy with penicillin of infants of group B streptococci positive mothers has no definite advantage upon delayed treatment.