Download 09702 - 台灣腎臟醫學會

1
Association between Nasal symptom score and various parameter in Asthmatic
Children in Taiwan
台灣地區氣喘兒童與過敏性鼻炎的關聯性
Kuo-Hsi Lee, Shyh-Dar Shyur, Szu-Hung Chu, Li-Hsin Huang, Yu-Hsuan Kao,
Shih-hann Tseng, Wei-Te Lei, Chia-Yi Lo, Chieh-Han Cheng
Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan
李國熙、徐世達、朱斯鴻、黃立心、高羽璇、曾詩涵、雷偉德、羅佳怡、程潔菡
台北馬偕紀念醫院小兒科部
Background: Allergic rhinitis and asthma are the two clinical disorders induced by an
IgE-mediated inflammation after allergen exposure Allergic rhinitis and asthma often
co-exist and appear to produce a continuum of one airway disease. Studies concerning
the effects of sinusitis and allergic rhinitis on asthma severity have had inconsistent
findings: some have shown an increased risk of severe asthma, whereas others have
not . OBJECTIVE: The study population consisted of persons with allergic rhinitis
were enrolled Patients whom had various degree of allergic rhinitis were compared
with severity of asthma, symptom score of asthma, specific IgE ( cat、dog、
D.pteronyssinus、D. farinae、cock、milk、egg、fish), total IgE, eosinophil, and lung
function. We attempted to find the connection of the degree of allergic rhinitis and the
other parameters
Methods: 301 patient aged 3.9-21 years-old ( average age: 8.4 years-old ) whom
diagnosed with allergic allergic rhinitis (AR) were enrolled. Various parameters
(including D.pteronyssinus, D. farinae, cat dander, dog dander and cockroach) also
were recorded. Allergic rhinitis symptom score used nasal total symptom scores
(NTSS) ranging 0–12 were obtained from patients or their families by using
four-point scales for sneezing, itching, rhinorrhea and for congestion (0: none; 1: mild;
2: moderate; 3: severe). According to their AR score, the patients were distributed to
two groups: (Low AR score group: 1-4; high AR score: 5-12). We compared the
different characters regarding asthma symptom score, asthma severity, total IgE level,
eosinophil count, specific IgE and pulmonary function parameters with two groups of
AR.
Results: Total 301 children diagnosed with allergic rhinitis were enrolled.into our
study. 172 patients with average age 8.3 years old were in low AR score group. 129
patients with average age of 8.5 years old were in high AR score group. There were
no differences in age, eosinophil counts, total IgE level, specific IgE, and pulmonary
function parameters amount two AR groups. However, we found that higher AR score
statistically had higher asthma severity and asthma symptom score .
Conclusions: In children with allergic asthma and co-exist allergic rhinitis, those with
more severe allergic rhinitis symptoms appear to have higher asthma severity and
asthma symptom score.
2
Compare the age and sex related differences of multiple allergic parameters in
children with allergic asthma
比較不同年齡性別過敏氣喘病兒的多種過敏指標
Chieh-Han Cheng, Shyh-Dar Shyur, Szu-Hung Chu, Li-Hsin Huang, Yu-Hsuan Kao,
Shih-haun Tseng, Wei-Te Lei, Chia-Yi Lo, Kuo-Hsi Lee
Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan
程潔菡、徐世達、朱斯鴻、黃立心、高羽璇、曾詩涵、雷偉德、羅佳怡、李國熙
台北馬偕紀念醫院小兒科部
Background: Previous studies had shown that sex and age influence the clinical
expression of asthma and allergic diseases. We sought to access the differences of
multiple allergic markers in different age and sex in those asthmatic children.
Methods: Children aged 4-18 years-old whom diagnosed with allergic asthma were
enrolled. Patients whom had allergic asthma were defined as patients with diagnosis
of asthma also had specific IgE positive to any one of the eight allergens with class
levels ≧1, (including D.pteronyssinus, D. farinae, cat dander, dog dander, cockroach,
egg, milk and fish). We compared the differences regarding asthma severity, asthma
score, CAP specific IgE test, total IgE level, eosinophil count and pulmonary function
parameters in different age and sex.
Results: Total 423 children (277 males and 146 females) diagnosed with allergic
asthma were enrolled. We used 8, 9, 10, 11 and 12 year-old as cut point to compare
the differences of multiple allergic markers between different groups. We found that
there were significant differences when using 12 year-old as cut point. There were
higher asthma severity, higher asthma score and higher specific IgE level to milk who
are younger than 12 year-old. There were higher PEFR%, higher FEF25~75% and
higher specific IgE level to cat dander, dog dander, cockroach who are older than 12
year-old. When younger than 12 year-old, boys had higher total IgE level and higher
specific IgE level to D.p., D.f., cat dander, dog dander and cockroach. When older
than 12 year-old, there was only difference in specific IgE level to fish.
Conclusions: During the course of growth and development, the expression of
allergic asthma is also changing simultaneously. We found younger children had
higher asthma severity and asthma score. Besides, younger children had more
opportunity that allergy to milk and egg, whereas older children allergy more to cat
dander, dog dander and cockroach. During younger ages, boys had higher specific IgE
levels and higher total IgE level.
3
The Correlation Between BMI and Various Parameters in Asthmatic Children
身體質量指數與多項氣喘參數在台灣地區氣喘病童的相關性。
Wei-Te Lei, Shyh-Dar Shyur, Li-Hsin Huang, Yu-Hsuan Kao, Chieh-Han Cheng,
Chia-Yi Lo, Kuo-Hsi Lee
Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan
雷偉德、徐世達、黃立心、高羽璇、程潔菡、羅佳怡、李國熙
台北馬偕紀念醫院小兒科部
Background: The pathophysiology and risk factors of asthma are various.
Overweight maybe one of those risk factors in recent studies. There was one study
concluded that overweight is positively associated with an increased risk of suspect
asthma in boys. Our study aims on the correlation bewteen BMI and various
parameters in asthmatic children.
Methods: We retrospectively collected patients of asthma and divided them into 3
groups according to their BMI. We compared the 3 groups about some asthmatic
parameters inclusive of eosinophil count, total IgE, pulmonary function, asthma
severity, asthma symptom score, serum specific IgE for D.pteronyssinus, D.farinae,
cockroach, milk, egg, fish, cat, dog. We tried to find statistical significances from the
3 groups. 396 patients (252 males, 144 females) aged from 5-17.6 year-old(mean: 8.5
year-old) diagnosed of mild intermittent to severe persistent asthma were enrolled.
Male and females were calculated separately. We divided each groups into 3
subgroups: at risk of overweight (BMI>85%), normal weight (5-85%), and
underweight (<5%) according to the CDC Growth Charts. The pulmonary function
included, PEFP%,FEV1,FEF25-75%.The specific IgE was recorded via Class 1-6.
Results: Among the 143 female, 3 subgroups of those showed no statistical
significance. While in the 3 subgroups of 252 males, with 88 at risk of
overweight(group A; mean age: 8.7), 144 normal weight(group B), and 20
underweight for the age. The numbers of underweight group is too small to enroll.
Some parameters showed statistically significance between the former 2 groups:
There was differences in FEV1(A>B: p=0.007), FEF25-75%(A>B: p=0.011), specific
IgE for egg(A<B: p=0.019). There was no statistically significant relation of
Eosinophil count, total IgE, PEFR%, asthma severity, asthma score, specific IgE for
D.p, D.f, cat, dog,cockroach, milk, fish, and age.
Conclusions: In asthmatic boys with at risk of overweight (BMI>85%), they seem to
have better pulmonary function and lower specific IgE for egg than those of normal
weight.
4
The relationship between the severity of asthma and the major factors of asthma
exacerbation in asthmatic children in Taiwan
台灣地區主要過敏誘發因子與氣喘的關聯性
Shih-hann Tseng, Shyh-Dar Shyur, Li-Hsin Huang, Yu-Hsuan Kao, Szu-Hung Chu,
Wei-Te Lei, Chieh-Han Cheng, Chia-Yi Lo, Tai-Kuo-Hsi Lee
Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan
曾詩涵、徐世達、黃立心、高羽璇、朱斯鴻、雷偉德、程潔菡、羅佳怡、李國熙
台北馬偕紀念醫院小兒科部
Background: The prevalence of asthma is increasing in Taiwan. Several factors
influence the severity of asthma, including atopy, environmental exposures, stress,
smoke, cool diet, and infection. The aim of this study was to identify the
epidemiology of asthma and the influence to asthma of major triggers. OBJECTIVE:
1. To recognize the epidemiology of season, atmospheric temperature and major
trigger factors of the severity of asthma. 2. To investigate whether major trigger
factors of asthma (viral Infection, cool diet, exercise, allergens) are associated with
the severity of asthma, asthma symptom score (0~16 scores) and pulmonary function
test (PEFR%, FEV1, FEF 25-75%).
Methods: 350 patients aged 2.1~17 years-old whom diagnosed as asthma were
enrolled. Information of the onset times and season of asthma exacerbation, the
prevalence rate of exacerbations of asthma, major triggers, asthma severity, asthma
symptom score and pulmonary function test were obtained during an interview with
the primary caretaker and the child. 222 asthmatic patients aged 5 ~17 years-old
underwent pulmonary function test.
Results: We found early morning was the most common onset time of asthma
exacerbation in Taiwan. There are predictable seasonal epidemics of exacerbations of
asthma, occurring in winter in children.Total 350 asthmatic children who have at least
one trigger factor were enrolled. We found the dominant trigger factor exacerbations
of asthma in children is viral infection. The cool diet is the 2nd common trigger factor
of asthma exacerbation. We found viral infection was significantly associated with the
severity of asthma (P=0.040) and was closely associated with the asthma symptom
score. We also demonstrated the cool diet have dominant relationship with the
severity of asthma(P=0.006) and the asthma symptom score(P=0.048). Other trigger
factors (exercise , allergens, smoke) had no relationship with asthma severity or the
asthma score. There was no association between major trigger factors of asthma and
pulmonary function test.
Conclusions: Viral infection is still the most common trigger factor of asthma
exacerbation and had dominant impact on asthma severity. Cool diet had dominant
association with asthma severity and asthma symptom score.
5
Epigenetic Profiles Associated with Maternal Atopy And Antenatal IgE
Production
新生兒上基因體譜與母親過敏和臍血抗體 IgE 上升相關
Kuender D. Yang{1}, Ho-Chang Kuo{3}, Jen-Chieh Chang{1}, Chieh-An Liu{1}, Te-Yao
Hsu{2}, Chia-Yo Ou{2}
Departments of Pediatrics1, Obstetrics2, Chang Gung Memorial Hospital-Kaohsiung
Medical Center. Chang Gung University3, Kaohsiung, Taiwan
楊崑德{1}、郭和昌{3}、張稔杰{1}、劉倢安{1}、許德耀{2}、歐家佑{2}
高雄長庚醫院 兒童內科 1 婦產科 2 與長庚大學臨床醫學研究所 3
Background: A growing body of evidence suggests that allergic sensitization could
occur in perinatal stage and correlate to the development of allergic diseases. In a
perinatal cohort study, we have found that the maternal effect of antenatal IgE
production was associated with interaction with gender and certain genetic
polymorphisms such as CTLA-4 +49A/G polymorphism (Clin Exp Allergy 37:680-7,
2007). Moreover, evidence has also shown that prenatal epigenetic programming is
involved in metabolic syndrome and hypertension. Thus, we hypothesized that
gene-environment interactions on epigenetic programming might begin early in the
fetal stage, and priming the later development of allergic diseases.
Methods: Employing whole genome epigenetic methylation array over 1536 CG sites
by Illumina BeadStation 500G Genotyping array, we initially analyzed 10 pairs of
cord blood DNA samples from newborns with and without CBIgE elevation
(≧0.5KU/L). After identifying those genes with more than 10% increase or decrease
of CG methylation, we used PCR analysis of bisulfite conversion of non-methylated
CG sites to validate CG site methylation in a cohort of 350 cord blood DNA samples.
Results: Results showed that 10 CG sites in 6 immune and redox genes had 10%
higher or lower methylation on the CG sites based on discrepancy between with and
without CBIgE elevation. The higher and lower CG methylation could be validated in
the PCR analysis of bisulfite conversion of non-methylated CG sites at the correlation
value (r=0.833-0.890, p<0.001). Further validation with 350 cord blood DNA samples,
we found that the methylation in promoter regions of GSTM1 gene was associated
with CBIgE elevation (≧0.5KU/L), and promoter CG site’s methylation of LMO2
gene was associated with maternal atopy.
Conclusions: This study suggests that prenatal epigenetic programming is
significantly associated with antenatal IgE production and maternal atopy. Further
studies are needed to validate whether the epigenetic programming is suitable for
early prediction and/or prevention of allergy sensitization in the future.
6
Drug Reaction: Case Study of the Adverse Drug Reaction Report in Cathay
General Hospital
國泰醫院藥物不良反應臨床案例研究
Chia-Jung Chen, Shih-Ping Hung, Hsi-Yen Lin1, Wu-Charng Chen
Department of Pediatrics, Cathay General Hospital; Department of Pharmacy, Cathay
General Hospital
陳嘉容、洪詩萍、林惜燕 1、陳五常
國泰綜合醫院醫院小兒科、藥劑科 1
Background: The primary purpose of spontaneous Adverse Drug Reaction Reporting
System(ADRRS) is to provide early warnings or ‘‘signals’’ of previously
unrecognized drug toxicity. Adverse drug reaction reporting system of Cathay General
Hospital was established in 2000. The suspected serious adverse drug reactions of the
medicaments are reported to National Taiwan ADR Reporting Center.
Methods: The immunopathogensis and the clinical manifestations of the 410 cases
reported to the ADRRS of Cathay General Hospital from 2006 to 2008 were analyzed.
Results: Drug reactions can be classified into immunological and nonimmunological
etiologies. Predictable, nonimmunological effects account for 48.2% of adverse drug
reactions whereas 51.7% of the reactions are immune-mediated drug hypersensitivity
reactions. The true drug hypersensitivity which involves IgE-mediated drug allergies
was account for 13% of all reactions. Among the cases of drug hypersensitivity
reactions, more than half (51.6%) of the reactions were morbilliform skin eruptions
while only 5.7% were urticaria. On the other hand, drug hypersensitivity reaction can
also be characterized by fever (13%), eosinophilia, and other extracutaneous
manifestations.
Conclusions: The adverse drug reporting system can provides the data of reaction
patterns of many drugs. Immune mediated drug hypersensitivity reaction accounts for
half of the adverse drug reactions in the reported data from Cathay General Hospital.
7
The Correlation between Total IgE Concentration, Eosinophil Count and
Various Parameters in Atopic Asthma Children
氣喘兒童 IgE 總量和嗜伊紅血球總數與多項氣喘參數的關聯性
Chia-Yi Lo, Shyh-Dar Shyur, Szu-Hung Chu, Li-Hsin Huang, Yu-Hsuan Kao,
Shih-Haun Tseng, Wei-Te Lei, Chieh-Han Cheng, Kuo-Hsi Lee
Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan
羅佳怡、徐世達、朱斯弘、黃立心、高羽璇、曾詩涵、雷偉德、程潔菡、李國熙
台北馬偕紀念醫院小兒科部
Background: Total IgE concentration and eosinophil count are usually elevated in
atopic asthma children. In ths study, we try to correlate the different levels of total IgE
concentration and eosinophil count with various parameters in children with atopic
asthma. OBJECTIVE: In ths study, we enrolled children with atoptc asthma. Patients
who had different levels of total IgE and eosinophil count were compared with
severity of asthma, symptom score of asthma, specific IgE ( cat、dog、
D.pteronyssinus、D. farinae、cock、milk、egg、fish), and lung function parameters
(including PEFR%, FEV1, FEF25-75%). We attempted to find the correlation
between levels of total IgE concentration, eosinophil count and the other parameters.
Methods: 394 patient aged 4-17.6 years-old ( average age: 8.4 years-old ) who
diagnosed with atopic asthma were enrolled. Various parameters mentioned above
also were recorded. According to their total IgE concentration, the patients were
distributed to two groups: (total IgE >=400 IU/mL; total IgE <400 IU/mL). According
to their eosinophil count, the patients were divided to other two groups: ( eosinophil
count>=400/&micro;L; eosinophil count<400/&micro;L). We compared these two
different groups of patients with high or low total IgE or eosinophil count levels with
their asthma severity, symptom score, specific IgE and pulmonary function
parameters.
Results: Total 394 children diagnosed with atopic asthma were enrolled in our study.
209 patients were in the group of total IgE higher then 400 IU/mL (including 400
IU/mL). 185 patients were in group of lower then 400 IU/mL. There were no
differences in asthma severity, asthma symptom score, specific IgE to milk, and
PEFR% among these two groups. However, we found that total IgE >=400 IU/mL
statistically had higher specific IgE to D.pteronyssinus 、D. farinae、cat、dog、cock、
egg、fish, higher eosinophil count, and lower FEV1 and FEF25-75% (p-value<=0.05).
On the other hand, 222 patients were in the group of eosinophil count higher then
400/&micro;L (including 400/&micro;L) . 172 patients were in group of eosinophil
count lower then 400/&micro;L. We found that eosinophil count >=400 /&micro;L
statistically had only higher specific IgE to D.pteronyssinus 、D. farinaee、dog and
total IgE.
Conclusions: In children with atopic asthma, those with IgE levels higher then 400
IU/mL are more allergic to D.pteronyssinus、D. farinae、cat、dog、cock、egg、fish,
have higher eosinophil count and have worse FEV1 and FE25-75%. The atopic
asthma children whose eosinophil count higher then 400 /&micro;L are more allergic
to D.pteronyssinus 、D. farinae、and dog, and have higher total IgE concentration.
Total IgE concentration seems prior to eosinophil count in prediction of more specific
IgE and worse lung function in atopic asthma children. Asthma severity and
symoptom score are no correlation between patients with different total IgE
concentration or eosinophile count.
8
The Clinical Application of Monoclonal Anti-IgE Antibody (Omalizumab) in
Persistent Severe Asthmatic Children
抗 IgE 單株抗體 Omalizumab 在嚴重持續型氣喘兒童的使用經驗
Hsin-Hung Chen1, Ren-Long Jan2, Yen-Lin Lin3, Jiu-Yao Wang4
｛1｝Department of Pediatrics, MaDou branch, Sin-Lau Hospital, Tainan, ｛2｝
Department of Pediatrics, Chi-Mei Medical Center, Liou-Yin Campus, Tainan, ｛3｝
Institute of Basic Medical Science, ｛4｝Department of Pediatrics, College of
Medicine, National Cheng Kung University, Tainan, Taiwan.
陳信宏 1、詹仁隆 2、林嬿琳 3、王志堯 4
｛1｝新樓醫院麻豆分院小兒科, ｛2｝奇美醫學中心柳營分院小兒科, ｛3｝成大
醫學院基礎醫學研究所, ｛4｝成功大學醫學院小兒部, 過敏免疫風濕科
Background: Immune responses mediated by IgE are important in the pathogenesis
of allergic asthma. A recombinant humanized monoclonal antibody (Omalizumab)
mast cells and basophils. We studied the efficacy of Omalizumab as a treatment for
persistent severe allergic asthma.
Methods: After a 4-week run-in period, we recruited 6 subjects (age range, 12 to 23
years) who required inhaled or oral corticosteroids (or both) to receive Omalizumab
(5.0 μg per kilogram of body weight per nanogram of IgE per milliliter)
subcutaneously for 16 weeks. The primary outcome measure was an improvement in
the asthma control test score, spirometry, and PEFR at the end of 16 weeks.
Results: We found the daily asthmatic symptoms and medications used for
controlling asthma were decreased in the 4 out of 6 treated patients. These responsive
patients also have increased their FEV1, PEFR, and ACT score. The two poor
responsive patients have poor changing rates in their bronchodilator tests, which
suggested the severe asthmatic status of airway remodeling. All 6 treated patients did
not have any adverse side effects receiving 16 weeks of Omalizumab treatments
Conclusions: A new invention therapy using recombinant humanized monoclonal
antibody directed against IgE may have potential as a treatment for subjects with
persistent severe allergic asthma in children.
9
Prevalence and Distribution of Allergic Sensitization in the Wheeze-ever First
Grade School Children in Taipei
曾經喘鳴之台北市國小一年級學童過敏原致敏之盛行率及分佈情況分析
Wei-Fong Wu1, Ching-Hsiang Chuang1, Kong-Sang Wan1, Shiuan-Jenn Wang2,
Winnie Yang3
Department of Pediatrics, Taipei City Hospital, Ren-Ai Branch1,Branch for Woman
and Children2, Yang-Ming Branch3.
吳維峯 1、莊晴翔 1、溫港生 1、王萱鎮 2、楊文理 3
台北市立聯合醫院小兒科仁愛院區 1，婦幼院區 2，陽明院區 3
Background: There is increasing evidence that the prevalence of asthma and other
allergic disease, such as allergic rhinitis and atopic dermatitis, has been increasing in
children in some countries during the past 4 decades, especially in Western countries.
The prevalence of asthma in children has also been increasing in Taipei, Taiwan.
Allergy plays a major role in the pathogenesis of asthma in children. The aim of this
study was to investigate the prevalence and distribution of allergic sensitization in the
wheezy first grade school children in Taipei city.
Methods: This study had a prospective cross-sectional design. . The survey was
conducted between September and December, 2007. ISAAC( International Study of
Asthma and Allergies in Childhood) questionnaire was sent to all the first grade
school children(n=26418) in Taipei . Of the 25097 respondents, 639 were excluded
due to incomplete answers. As a result, the number of valid questionnaires for the
analysis was 24458. Those children whose parent answered yes to the question “Has
your child ever had wheezing or whistling in the chest at any time in the past?” and
agreed to join the study were recruited. A blood sample was taken from each included
child for specific IgE antibody determination ( Phadiatop) using a Pharmacia CAP
System. The sera were stored in aliquots at -70℃. Thawed sample were tested in large
batches. If a positive result was found, an additional 6 group mix (animal epidermal,
house dust, mold, seafood, children’s food, pollens) and further 32 specific IgE tests
were performed
Results: The prevalence of wheeze ever was 20.34%(4975/24458). A total of 2030
children were included in this study. The Phadiatop test was positive in 73.89% of
these children. The positive rates in the 6 group mix allergens were: house dust 92%,
animal epidermals 56%, children’s food 47%, sea food 25%, mold 4%, pollen 4%.
Among the specific IgE tests, Dermatophagoides. pteronyssinus was the commonest
allergen (90.79%), followed by Dermatophagoides farinae (88.24%), dog danders
(28.95%), egg white (24.23%), milk (22.45%), shrimp (21.44%), Ameriaca cockroach
(16.71%), German cockroach (15.48%), cat danders (8.67%), wheat(6.66%).
Conclusions: The use of specific IgE antibody determinations improves the clinical
management of patients with allergy related symptoms in primary care. In this study,
allergy sensitization rate was high in the 6 to 8-year-old wheeze-ever children in
Taipei. House dust eg: D. pteronyssinus was the major allergen. This data allowed
advice to be given on specific allergen avoidance.
10
Randomized, Open Label Trial Comparing Xyzal and Xyzal with Lactobacillus
johnsonii EM1 for Treating Perennial Allergic Rhinitis in Children Aged 7-12
Years
隨機開放比較 Xyzal 和 Xyzal 合併 Lactobacillus johnsonii EM1 對過敏性鼻炎
7-12 歲兒童的療效
Chi-Yung So, Yeak-Wun Quek, Pei-Fen Liao, Hai-Lun Sun, Ko-Huang Lue
Department of Pediatrics, Chung Shan Medical University Hospital
蘇志勇、郭業文、廖培汾、孫海倫、呂克桓
中山醫學大學附設醫院小兒部過敏免疫科
Background: Allergic rhinitis is a common childhood disease whose prevalence is
increasing worldwide. It persists for many years if untreated and may result not only
in loss of school days for the child but also in lost productivity of parents or
caregivers, who may miss work. Histamine is the best known mediator, shown to
cause symptoms of AR. Nonsedating antihistamines have become the standard
first-line therapy in treating AR. Levocetirizine (Xyzal) is a new-generation selective
H1-antihistamine approved for the treatment of allergic rhinitis and chronic idiopathic
urticaria. Supplementary consumption of Lactobacillus johnsonii EM1 may
temporarily alter the intestinal microflora of infants and children to produce a
beneficial effect in treating or preventing allergic disorders of the gastrointestinal tract
and other allergic disorders.
Methods: The purpose of this present study was to compare the clinical efficacy
between Xyzal and Xyzal with Lactobacillus johnsonii EM1 for treating perennial
allergic rhinitis in children aged 7-12 years. Fifty six children aged 7 to 12 years
fulfilled the criteria for the study and they were with moderate to severe perennial
allergic rhinitis for at least one year. We used a randomized, open label trial
comparing Xyzal and Xyzal with Lactobacillus johnsonii EM1 in perennial allergic
rhinitis patients with mite allergy, aged 6 to 12 years old, assigned to 2 treatment
groups for 12 weeks randomly. The effects of the two agents were compared with the
Pediatric Rhinoconjunctivitis Quality of Life Questionnaire and the total symptom
score of diary card. Nasal peak expiratory flow rate, FVC, FEV1 and laboratory
examinations including serum immunoglobulin E level, eosinophilic cationic protein,
blood eosinophil counts eosinophil percentage in a nasal smear IL4, IL10,
interferonResults: The results revealed that both Xyzal and Xyzal with Lactobacillus johnsonii
EM1 improved progressively total symptom score during 3-month therapy period,
compaed with the run-in period in both groups at weeks 4, 8, 12 (P<0.05), and xyzal
with Lactobacillus johnsonii EM1 appeared to be more efficacious than Xyzal at week
8(P<0.05) and week 12 (P<0.05). The Pediatric Rhinoconjunctivitis Quality of Life
Questionnaire score showed significant decreased in both groups (P<0.05), but there
was no statistic significant difference between both groups (P=0.193). The eosinophil
proportion in a nasal smear significantly decreased in both groups (P<0.05), but there
was no statistic significant difference between both groups (P=0.2013) Both groups
showed significant improvement in nasal peak expiratory flow rate at week
4,12(P<0.01), and Xyzal with Lactobacillus johnsonii EM1 appeared to be more
efficacious than Xyzal at week 8(P<0.05). FVC and FEV1 were improved in both
groups at weeks 4, 8, 12(p<0.05), but there were no significant difference between
two groups, except FEV1 in Xyzal with Lactobacillus johnsonii EM1 group was
superior than Xyzal group at weeks 12(p<0.05). Cytokines in both groups were not
finished yet, but we will present later. There was no serious adverse event been
recorded both groups.
Conclusions: The 12-week treatment program showed that Xyzal with Lactobacillus
johnsonii EM1 was more effective than Xyzal. Further studies on large groups of
patients are necessary to confirm these results and to evaluate the immunology
mechanisms
11
Compare Acute Sinusitis in Children with and without Nasal Irrigation
鼻腔灌洗對治療兒童急性鼻竇炎的療效
Fong-Fong Lim, Yun-Hu Wang, Min-Sho Ku, Hai-Lun Sun, Ko-Huang Lue
Department of Pediatrics, Chung Shan Medical University Hospital
林芳芳、王雲虎、顧明修、孫海倫、呂克桓
中山醫學大學附設醫院小兒部過敏免疫科
Background: Nasal irrigation has been used as an adjunctive therapy of sinonasal
disease including acute/chronic sinusitis and allergic rhinitis. Several published
articles reported it also improves clinical sinus symptoms.
Methods: We included 69 participants with acute sinusitis. 30 of 69 participants
underwent normal saline nasal irrigation. 39 of 69 participants were not receiving
nasal irrigation. All participants performed nasal peak expiratory flow rate (nPEFR)
test, nasal smear examination, radiography (Water`s projection) and requested to
complete the Pediatric Rhinoconjunctivitis Quality of Life Questionnaires (PRQLQ)
at the baseline visit. All participants were requested to record the symptom diary card
every day and were followed up every 1 week during this period. A physical
examination, nasal smear and nPEFR were performed at each visit, and all daily diary
cards collected. At the final visit, the symptoms diaries were reviewed and
participants were requested to complete the PRQLQ again. The nPEFR, radiography
(Water`s projection) and nasal smear were also repeated.
Results: Normal saline irrigation group significantly improved mean PRQLQ values
and nPEFR values at medium (T = 2.816, P<0.05) and final period (T = 2.767, P<0.05)
compared with the other group. Although there were no statically significant
improving rate of radiography (Water`s projection) in among two groups (T = 0.545,
P>0.05), but normal saline irrigation group was better than the other group. 27 of 66
(40.9%) participants with atopy, 16 of 27 (53.33%) participants underwent normal
saline irrigation. Normal saline irrigation atopy group significantly improved
rhinorrhea, nasal congestion, throat itching and sleep quality symptoms compared
with non-irrigation atopy group. Normal saline irrigation atopy group significantly
improved nPEFR values at final period.(Z = 2.53, P<0.05)
Conclusions: This study evidence that normal saline nasal irrigation improves
Pediatric Rhinoconjunctivitis Quality of Life and decreases acute sinusitis symptoms.
Nasal irrigation is an effective adjunctive treatment for pediatric acute sinusitis.
Normal saline nasal irrigation in atopy children also improves allergic-related
symptoms. We may need larger, longer and extended study to assess the conclusion.
12
Effect of endocrine disruptor chemicals on cytokine expression in human
plasmacytoid dendritic cells via epigenetic regulation
環境荷爾蒙經由表觀基因調控對於人類漿樹突細胞所分泌之細胞激素的影響
Chih-Hsing Hung1, Yu-Te Chu1, Kuender D. Yang2, Yuh-Jyh Jong1, Shau-Ku Huang3
1
Department of Pediatrics, Kaohsiung Medical University Memorial Hospital, 2
Chang Gung Children’s Hospital in Kaohsiung, Kaohsiung, Taiwan, 3 Asthma and
Allergy Center, Johns Hopkins University
洪志興 1、朱育德 1、楊崑德 2、鐘育志 1、黃嘯谷 3
高雄醫學大學附設醫院小兒部 1 高雄長庚兒童醫院 2 美國約翰霍普金斯大學氣
喘暨過敏中心 3
Background: Dendritic cells (DC) are key regulators of adaptive immunity with the
potential to induce T cell immunity or tolerance. Endocrine-disrupting chemicals
(EDCs) are ubiquitous in environment and the impact of EDCs exposure on human
health is receiving increasingly focused attention. EDCs have been reported to be
associated with allergy in children. Plasmacytoid DCs (pDCs) play an important role
in the regulation of various diseases, such as allergic, autoimmune diseases and cancer.
The influences of EDCs on the expression of cytokines in pDCs need to be defined.
To this end, the regulatory role of EDCs, the influence of nonylphenol (NP) and
4-octylphenol (4-OP), two EDCs, on cytokine expression in human circulating pDCs
and the subsequent effect on influencing T cell polarization were investigated.
Methods: Circulating pDCs were magnetically sorted with BDCA-4 cell isolation kits
respectively from human peripheral blood mononuclear cells of five patients with
allergic rhinitis, and treated with varying concentrations of NP and 4-OP with or
without the addition of CpG oligonucleotides or an estrogen receptor (ER) antagonist,
ICI 182,780. The levels of cytokines, TNF-α and IL-10 were measured by ELISA.
Cell supernatant were collected from CD4+ T cells co-cultured with NP-treated pDCs
for 5 days to determine IL-13 and IFN-γ expression. Western blotting and chromatin
immunoprecipitation (ChIP) assay were performed to explore the intracellular
signaling.
Results: NP and 4-OP oculd induce the expression of TNF-α, but suppress IL-10
production in pDCs in allergic patients. This effect of inducing TNF-α was reversed
partially by the addition of an estrogen receptor antagonist, ICI 182,780. Co-cultured
with NP- or 4-OP- treated pDCs, IFN-r production of T cell was increased, but no
effect on IL-13 expression. SB203580 (p38-MAPK inhibitor) suppressed NP-induced
TNF-α expression in pDCs. NP alone or with CPG could enhance p38 expression by
pDCs. NP-induced TNF-α expression in pDCs was inhibited by anacardic acid, a
histone acetyltransferase inhibitor. NP and 4-OP could enhance expression of histone
acetylation and tri-methylation in TNF-α promoter region in pDCs.
Conclusions: NP and 4-OP enhanced TNF-α, but suppressed LPS-induced IL-10 by
human pDCs via the ER receptor, in part, and the p38 MAPK pathway and histone
acetylation and tri-methylation. NP- treated pDCs suppressed Th1 cytokine
expression.
13
Effect of prostaglandin I2 analog on TNF-α expression via epigenetic regulation
in human monocyte-derived dendritic cells
前列腺素 I2 類構物經由表觀基因調控對於人類樹突細胞所分泌之腫瘤壞死因子
表現的影響
Chih-Hsing Hung1, Yu-Te Chu1, Kuender D. Yang2, Shau-Ku Huang3
1
Department of Pediatrics, Kaohsiung Medical University Hospital, 2 Chang Gung
Children’s Hospital in Kaohsiung, Kaohsiung, Taiwan, 3 Asthma and Allergy Center,
Johns Hopkins University
洪志興 1、朱育德 1、楊崑德 2、黃嘯谷 3
高雄醫學大學附設醫院小兒部 1 高雄長庚兒童醫院 2 美國約翰霍普金斯大學氣
喘暨過敏中心 3
Background: Dendritic cells (DCs) are the major antigen-presenting cells involved in
the induction of the primary immune response and play a critical role in asthma via
cytokines production. Prostaglandin I2 (PGI2) is a metabolite of arachidonic acid and
may have anti-inflammatory functions. Iloprost, a PGI2 analog and well-accepted
medication for human pulmonary arterial hypertension, has been recently shown to
suppress the cardinal features of asthma via inhibition of mice airway dendritic cell
function, however, little is known about its role in the function of human
monocyte-derived DCs (MDDCs). Epigenetic regulation is important for cytokine
expression. Therefore, we also investigated whether PGI2 analog influenced cytokine
expression in MDDCs via epigenetic regulation.
Methods: Human MDDCs were treated with varying concentrations of iloprost and
treprostinil, two PGI2 analogs, with or without the addition of Toll-like receptor
(TLRs) agonists, poly I:C (for TLR3) or I prostanoid (IP) receptor and E prostanoid
(EP) antagonists. The levels of cytokines, TNF-α were measured by ELISA. Western
blotting and chromatin immunoprecipitation (ChIP) were performed to explore the
intracellular signaling of TNF-α regulation in MDDCs.
Results: Iloprost could suppress, in a dose-dependent manner, poly I:C-induced
TNF-α and IL-12 productions in MDDCs. This effect was reversed, partly by the
addition of IP and EP receptors antagonists, and also forskolin, a cAMP activator,
conferred a similar modulating effect as that noted in iloprost-treated MDDCs.
SB203580 (p38-MAPK inhibitor; 1-5 μM) suppressed poly I:C-induced TNF-α
expression and iloprost reduced poly I:C-induced pp38 expression in mDCs. ChIP
demonstrated Iloprost reduced poly I:C-induced trimethylated H3K4 and
trimethylated H3K9 in TNF-α promoter and intron regions. Iloprost suppressed poly
I:C-induced nuclear MLL and WDR5 expression in MDDCs.
Conclusions: Iloprost suppressed TLR-mediated TNF-α production of human
MDDCs via, in part, the IP and EP receptors and the cAMP, p38, MLL and
trimethylated H3K4 pathway.
14
The Significance of Natural Resistance Associated Macrophage Protein-1
(NRAMP1) Polymorphisms in Taiwanese Children with Asthma
自然抗性相關巨噬細胞蛋白基因多型性在台灣兒童氣喘病的重要性
Tsung-Chieh Yao1, Yi-Chan Tsai2, Liang-Shiou Ou1, Li-Chen Chen1, Jing-Long
Huang1
Division of Allergy, Asthma and Rheumatology, Department of Pediatrics, Chang
Gung Children’s Hospital1; Department of Pediatrics, Chang Gung Memorial Hospital
at Chia-Yi2, Taoyuan and Chiayi, Taiwan
姚宗杰 1、蔡宜展 2、歐良修 1、陳力振 1、黃璟隆 1
林口長庚兒童醫院兒童內科部兒童過敏氣喘風濕科 1、長庚紀念醫院嘉義分院小
兒科 2
Background: Based on the hygiene hypothesis stating that lack of early childhood
bacterial infections would favor development of asthma, we hypothesize that Natural
Resistance Associated Macrophage Protein-1 (NRAMP1) gene controlling
antibacterial resistance can be of significance in the pathogenesis of asthma. The
objective of this study is to systemically search for polymorphisms in the NRAMP1
gene and investigate the association of NRAMP1 gene variants and childhood asthma
in Taiwanese children.
Methods: One hundred and six children with asthma were recruited from the Chang
Gung Children’s Hospital. One hundred and six age-comparable healthy children
without asthma or other allergic diseases were recruited as normal controls. Their
genomic DNA were extracted from peripheral blood and genotyping was performed
by either DNA auto-sequencing or MALDI-TOF/MS method.
Results: In a systemic search for polymorphisms in the promoter and gene-coding
region of NRAMP1 gene in Taiwanese population, we identified seven
polymorphisms (two in promoter, three in exons, one in intron and one in 3’UTR).
The genotype frequencies of the seven polymorphisms in the NRAMP1 gene for
asthmatic children and normal controls were compared. A significant difference was
found for the genotype frequency of NRAMP1 -236C/T polymorphism between
asthmatic children and normal controls (P = 0.020).
Conclusions: Our preliminary results revealed that the NRAMP1 -236C/T
polymorphism protects against childhood asthma in Taiwanese population. Further
studies are necessary to elucidate the influence of these NRAMP1 gene
polymorphisms on phenotypes and severity of asthma, or even other autoimmune and
infectious diseases in Taiwanese population.
15
Antiphospholipid Antibodies and Antiphospholipid Syndrome in Children and
Adolescents with Systemic Lupus Erythematosus
兒童及青少年全身性紅班性狼瘡病人抗磷脂質抗體及抗磷脂質症候群之研究
Yi-Ching Lin2, Hsin-Hui Yu1, Li-Chieh Wang1, Yao-Hsu Yang1, Bor-Luen Chiang1
Department of Pediatrics, National Taiwan University Hospital (1); Lo-Hsu
Foundation, Inc., Lotung Poh-Ai Hospital (2)
林怡青 2、俞欣慧 1、王麗潔 1、楊曜旭 1、江伯倫 1
國立台灣大學醫學院附設醫院小兒部 (1); 財團法人羅許基金會羅東博愛醫院
(2)
Background: Antiphopholipid syndrome (APS) is defined by the presence of one or
more clinical episode of arterial or venous thrombosis in any tissue or organ or by the
occurrence of repeated fetal loss, associated with the presence of antiphospholipid
(aPL) antibodies be found positive on two or more occasions. APS is one of the
diagnosis criteria for SLE. Our study aimed to investigate the manifestation of APS
syndrome and the frequency of aPL antibodies in lupus children.
Methods: 78 SLE patients who fulfilled the classification criteria of the American
College of Rheumatology were included. The diagnosis of APS was established in
accordance with ACR criteria. Laboratory data and Clinical date regarding the
manifestations of SLE and APS were collected retrospectively from medical records.
Antiphospholipid antibodies were assayed using IMUCLONE&reg; aPL IgG ELISA
kit. Anticardiolipin antibodies (ACA) were assayed using AUTOZYME&reg; ACL
anticardiolipin IgG and IgM sandwich immunoassays. The statistical analysis was
performed using the chi-square, Fisher’s exact test, and t-test for two independent
samples. Statistical significance was defined as P < 0.05 and all of the statistics were
computed using the SPSS program (version 12.0 for Windows).
Results: The patients’ mean age at disease onset was 13 years, ranging from 4 to 18
years. The mean period of follow-up was 8.3 years (ranging form 2 months to 31
years). Of the 78 children and adolescents with SLE studied, aPL antibodies were
positive in 42.3% of the cases. Antiphospholipid syndrome was diagnosed in seven
((9.0%) of the 78 SLE patients. Four patients had arterial thrombosis (stroke, two;
transient ischemic attack, one; amaurrosis fugax, one; lower limb vessel occusion,
two), one present with venous thrombosis (IVC thrombosis) and three had
involvement of small caliber vessels (osteonecrosis, one; transverse myelitis, two).
Recurrences were observed in two of seven cases (28.6%).
Conclusions: Antiphospholipid antibodies were positive in 42.3% of our Chinese
SLE patients. The frequency of antiphospholipid syndrome in lupus children is 9% in
the cases, and arterial thrombosis is the main manifestations of APS.
16
Clinical Aspects, Immunologic Assessment, and Genetic Analysis in Taiwanese
Children with Hemophagocytic Lymphohistiocytosis
台灣巨噬細胞症候群的臨床表徵免疫功能評估及基因分析
Wen-I Lee1, 2, Jing-Long Huang1, 2, Iou-Jih Hung1, 3, Tang-Her Jaing1, 2, Li-Chen
Chen2, Chao-Ping Yang1, 3, Kuo-Wei Yeh2, Shy-Jae Lin2, Chih-Jung Chen4, Shin-Pai
Li5
Primary Immunodeficiency Care and Research (PICAR) Institute 1, and Departments
of Pediatric Allergy, Immunology, and Rheumatology 2, Pediatric
Hematology/Oncology 3, Pediatric Infection 4, and Microbiology and Immunology 5,
Chang Gung Children’s and Memorial Hospital, Chang Gung University College of
Medicine, Taoyuan, Taiwan.
李文益 1, 2、黃璟隆 1, 2、洪悠紀 1, 3、江東和 1, 2、陳力振 2、揚兆平 1, 3、葉國偉 2、
林思偕 2、陳志榮 4、黎欣白 5
長庚兒童醫院先天性免疫缺陷照護暨研究中心 1, 兒童過敏免疫風濕科 2, 兒童血
液腫瘤科 3, 兒童感染科 4, 長庚大學微免系 5
Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening
syndrome characterized by immune disturbance associated with certain genetic
defects. This study aimed to define the clinical spectrum, immunology, and candidate
genes in HLH in Taiwanese patients.
Methods: The medical records of children who met the updated diagnostic criteria
and had confirmed hemophagocytosis by bone marrow aspiration between 1992 and
2007 were retrospectively evaluated. The clinical course and prognosis were analyzed.
Quantitative immunoglobulin, lymphocyte subsets, cytotoxicity to K562 cells,
intracellular natural killer perforin expression, and candidate genes including
SH2D1A, PFR1, Mun13-4, and STX11 genes were also investigated.
Results: Thirty-two patients (16 male) were evaluated during the 15-year period. The
underlying diseases were acute lymphoblastic leukemia, systemic lupus
erythematosus, natural killer malignancy, juvenile idiopathic arthritis, and
Chediak-Higashi syndrome. Epstein-Barr virus (EBV)-associated HLH was present in
12 patients, 6 of whom died, while 12 of 20 non–EBV-associated patients died despite
aggressive polychemotherapy. Extreme immunoglobulin values occurred in 3 fatal
cases. There was decreasing percentage of CD4, CD1656, and B-memory cells and
increasing CD8, activated lymphocyte, and T-memory cells among the patients.
Cytotoxicity in 14 patients and intracellular perforin expression in 13 were diminished
but restored to borderline normal range during the convalescent stage. None of the
mutations of SH2D1A, PFR1, Mun13-4, and STX11 genes were found.
Conclusions: In the treatment of Taiwanese HLH patients, aggressive chemotherapy
in EBV-associated patients and stem cell transplantation in non–EBV-associated
patients are recommended to improve survival. Individualized immune dysregulation
instead of the well-known candidate genetic mutations can explain the genetic
variation in our cohort.
17
Serum Levels of Resistin in Allergic Rhinitis and Its Relationship with Disease
Severity
過敏性鼻炎患者血清脂肪激素 resistin 濃度以及與疾病嚴重度相關性的探討
Kai-Chung Hsueh, Ching-Yuang Lin
Children’s Medical Center, China Medical University Hospital
薛凱中、林清淵
中國醫藥大學附設醫院 兒童醫學中心
Background: Resistin is a cystein-rich secretory adipokine. It is proposed to have
proinflammatory properties in humans.The aim of this study was to evaluate serum
resistin levels in children with allergic rhinitis and to investigate its association with
clinical disease severity, parameters of atopy and pro- /anti-inflammatory cytokines.
Methods: A prospective, randomized, case-controlled study was performed on 50
patients with persistent allergic rhinitis and 30 healthy controls with similar age, sex
and body mass index in a tertiary center. Serum levels of resistin, parameters of
atopy and cytokines were analyzed. The nasal symptom scores were evaluated and
patients were classified into mild (n = 20) and moderate-severe (n = 30).
Results: Serum resistin levels were significantly higher in the allergic rhinitis group
(median [interquartile range]= 16.13 [10.43-25.09] ng/ml) than in the control group
(median [interquartile range]= 10.43 [7.79-14.81] ng/ml) (P < 0.001).
Serum levels of resistin went hand in hand with disease severity as they were
significantly higher in moderate-severe (median [interquartile range]= 21.93
[11.94-29.99] ng/ml) than mild (median [interquartile range]= 14.47 [8.92-16.77]
ng/ml) persistent allergic rhinitis (P = 0.01). In addition, they correlated positively
with nasal symptom scores (r = 0.74; P < 0.001). A significant positive correlation
was observed between serum levels of resistin and IL-6 (r = 0.358; P = 0.011).
Conclusions: Serum resistin levels appear to be an additional objective marker that
may be useful for assessing allergic rhinitis severity in children. Resistin may
represent a novel link between inflammation and allergic rhinitis.
18
The Comparison of Budesonide and Fluticasone in Pediatric Asthma Patients
Budesonide 與 fluticasone 治療氣喘病童的臨床, eNO, 血清 TNF-a 與趨化激素的
比較
Lin-Yu Kuo1, Chih-Hsing Hung1, Jiunn-Ren Wu2, Yuh-Jyh Jong1, Yu-Te Chu1
Department of Pediatrics, Kaohsiung Medical University Hospital 1 ; Department of
Pediatrics, Kaohsiung Municipal Hsiaokang Hospital, Kaohsiung 2
郭怜玉 1、洪志興 1、吳俊仁 2、鐘育志 1、朱育德 1
高雄醫學大學附設中和紀念醫學小兒部 1; 高雄小港醫院小兒科 2
Background: Serum levels of cytokines and chemokines are associated with asthma
during attacks and remissions. In the pediatric asthma patients, the information of the
effects on serum levels of cytokines and chemokines before and after inhaled
corticosteroids therapy are still little. In this study, two inhaled glucocorticoids,
budesonide and fluticasone propionate were used in pediatric patients with
mild-to-moderate asthma. Parameters such as the peak expiratory flow (PEF), exhaled
nitric oxide (eNO), serum cytokines and chemokines were measured in order to
compare the pharmaceutical effects of the two inhaled steroids.
Methods: This was a randomized, open label, observer-blinded study. The pediatric
patients aged 5-18 years old were enrolled and received 3 months of treatment with
inhaled budesonide 200 mcg/puff, administered twice daily, or fluticasone propionate
250 mcg/puff, two puff per day. PEF, eNO, Asthma Control Test (ACT), serum level
of TNF-α, TARC, and IP-10 were measured at before and monthly for 3 months.
Results: We had 6 patients use budesonide, and 8 patients use fluticasone. After 3
months of medication, both groups had improved PEF. The budesonide group showed
better improvement than the fluticasone group in PEF in the first month, though not
significantly different. After treatment, the ACT score in both groups showed well
controlled except one in the fluticasone group. However the fluticasone group had
significant reduction of eNO in the first month than the budesonide group. Besides,
the fluticasone group had lower plasma IP-10, TNF-α and TARC than the budesonide
group.
Conclusions: We had observed that the budesonide group had quick improvement in
lung function and clinical scores than the fluticasone propionate group. But the
fluticasone propionate had better anti-inflammatory effect than the budesonide group.
We deduced that different inhaled steroids possess its own clinical and laboratory
effects due to device design and pharmacological effects.
19
Treatment of Acute Myeloid Leukemia with Hyperleukocytosis without
Leukoreduction Procedure
治療白血球數極高之急性骨髓性白血病非以白血球減除術
Ting-Chi Yeh, Hsi-Che Liu, Lin-Yen Wang, Jen-Yin Hou, Shu-Huey Chen,
Der-Cherng Liang
Division of Pediatric Hematology-Oncology, Department of Pediatrics, Mackay
Memorial Hospital
葉庭吉、劉希哲、王麟燕、侯人尹、陳淑惠、梁德城
馬偕紀念醫院小兒血液腫瘤科
Background: Patients with acute myeloid leukemia (AML) and hyperleukocytosis
are associated with early complications and have a worse outcome and are often
treated with leukoreduction procedure. In this study, we reported our experience
without leukoreduction procedure.
Methods: From November 1, 1995, to January 31, 2008, 60 children under the ages
of 15 years of age with de novo AML other than acute promyelocytic leukemia (APL)
were treated at Mackay Memorial Hospital (MMH). Fourteen patients had initial
leukocyte counts 100 × 10 9/l. One patient who was deeply comatous at diagnosis did
not receive chemotherapy and was excluded form survival analysis. All patients were
treated with 2 consecutive protocols, MMH-AML-96 and TPOG-AML-97A. Prompt
chemotherapy was started within hours while leukoreduction procedure was not
performed. Probabilities of survival were estimated by the Kaplan-Meier method with
standard errors. Univariate analysis was performed using the log-rank test.
Results: The median age of patients with hyperleukocytosis was 7.6 years (range
0.5-15 years), and the median initial leukocyte count was 184 × 10 9/l (range 117-475
× 10 9/l). The most frequent FAB subtype was M4 (5 patients) followed by M5 and
M1 (3 patients each), M2 (2 patients), and M0 (1 patient). Two patients had
t(9;11)/MLL-AF9, one t(11;19)/MLL-ELL, one inv(16)/CBFβ-MYH11, one
monosomy 7, and 9 patients had a normal karyotype. Seven patients had one or more
early complications before or during the first 2 weeks of chemotherapy including 3
neurologic, 4 respiratory, 6 renal, 3 sepsis, and 4 bleeding events. As of January 10,
2009, patients with and without hyperleukocytosis had similar complete remission
rates, 92% vs 100% (p=0.22). However, patients with hyperleukocytosis had a lower
5-year survival, 43% vs 70% (p=0.07), and the 5-year event free survival, 39% vs
65% (p=0.04). In patients with hyperleukocytosis after initiating chemotherapy, the
median duration of blast appearance in peripheral blood was 192 hours and patients
who relapsed or died were associated with a longer duration than those who had better
outcome, 222 vs 105 hours. The median duration of leukocyte count greater than 10×
10 9/l was 72 hours and, patients who relapsed or died were associated with a longer
duration than those who had better outcome, 80 vs 65 hours.
Conclusions: Without leukoreduction procedure, patients with hyperleukocytosis
treated with prompt chemotherapy can have satisfactory initial treatment results.
20
Hepatoblastoma: a Single Institution’s Experience of 34 Cases
肝母細胞瘤– 一單一醫療機構 34 位病例之經驗
Tang-Her Jaing1, Ming-Horng Tsai1, Chao-Ping Yang1, Iou-Jih Hung1, Jin-Yao Lai2,
Chuen Hsueh3
Divisions of Hematology and Oncology1, Department of Pediatrics, Department of
Pediatric Surgery2, Department of Pathology3, Chang Gung Children’s Hospital,
Chang Gung University, Linkou
江東和 1、蔡明宏 1、楊兆平 1、洪悠紀 1、賴勁堯 2、薛純 3
長庚大學，林口長庚紀念醫院兒童醫學中心，兒童血液腫瘤科 1，兒童外科 2，
解剖病理科 3
Background: Aim of the study was to review our experience in the management of
hepatoblastoma in children over the past 18 years.
Methods: A cohort of 34 children with hepatoblastoma managed in our institution
between February 1990 and September 2008. There were 18 males and 16 females
with a median age of 10 months at diagnosis (range, 1-169 months). We reviewed the
clinical presentation, serum AFP level at diagnosis, histological subtype, treatment,
and outcomes. The survival probability was calculated using the Kaplan–Meier
method.
Results: The median AFP level at diagnosis was 76,838 ng/ml (range, 467-2,420,000).
A palpable mass in the abdomen was the presenting symptom in 30 patients (88.2%).
Of those 34 patients, 7 had documented pulmonary metastasis. Chemotherapy
regimens included the SIOPEL study protocols. Six patients (18%) received an
extended right hemi-hepatectomy, 13 (38%) had right hemi-hepatectomy, 4 (12%) had
left hemi-hepatectomy, 1 (3%) had extended left hemi-hepatectomy, and 4 (12%) had
bisegmentectomy. One patient subsequently underwent liver transplantation for
unresectable disease. The post-chemotherapy histological types encountered as per the
SIOPEL Liver Study Group were as follows: Purely fetal – 1, Embryonal and mixed
embryonal/fetal subtype – 12, Macrotrabecular – 1, Mixed epithelial and
mesenchymal type – 12. During follow-up, 6 patients died of progressive disease and
2 died of operative mortality. Four of them had pulmonary metastases. The median
survival time was 28 months, and 5-year overall survival and progression-free
survival rates were 67.9% and 67.2%, respectively.
Conclusions: The development of pulmonary metastases is a factor of poor prognosis.
New treatment strategies are needed for patients with advanced hepatoblastoma.
21
Genetic Analysis of Two Families with Infantile Malignant Autosomal Recessive
Osteopetrosis
惡性嬰兒型骨質石化症患者之家族基因分析
Yu-Chun Chiu1, Yung-Li Yang1,2, Wuh-Liang Hwu1,3, Yin-Hsiu Chien1,3, Ni-Chung
Lee1,3, Dong-Tsamn Lin1,2, Kai-Hsin Lin1, Shian-Tarng Jou1, Meng-Yao Lu1, Yi-Ning
Su3
Department of Pediatrics(1), Department of Laboratory Medicine(2) , Department of
Medical Genetics(3), National Taiwan University Hospital and National Taiwan
University College of Medicine, Taipei, Taiwan
邱郁淳 1、楊永立 1,2、胡務亮 1,3、簡穎秀 1,3、李妮鍾 1,3、林東燦 1,2、林凱信 1、
周獻堂 1、盧孟佑 1、蘇怡寧 3
國立台灣大學醫學院附設醫院 小兒部(1),檢驗醫學部(2),基因醫學部(3)
Background: Osteopetrosis , a genetic disease characterized by osteoclast failure , is
classified as three groups : infantile malignant autosomal recessive osteopetrosis
(ARO), intermediate autosomal recessive osteopetrosis (IRO), and autosomal
dominant osteopetrosis (ADO) . Patients with ARO are the most severely affected
characterized by severe hematological and bone manifestation in the neonatal period.
Genetic analysis is important to confirm the diagnosis and for further genetic
counseling for the next pregnancy.
Methods: The genomic DNA of two families with baby diagnosed as osteopetrosis
clinically are collected . The first patient’s mother had pregnancy at gestational age of
10 weeks thus the sibling’s amniotic fluid was also collected . Denaturing
high-performance liquid chromatography(DHPLC) were used for both families and
High resolution melting analysis(HRM) was applied in one family. The fragment
showing abnormal DHPLC or HRM pattern were further send to Sequence analysis to
identify the mutation.
Results: The first case has the mutation on TCIRG1 gene 【c.1555-2 A>C / c.1555-2
A>C】. His parents’ and the sibling’s TCIRG1 gene genotype are all carrier【c.1555-2
A>C / WT】. The CLCN7 gene genotype is【WT / WT】 The second case has the
mutation on TCIRG1【c.1213 G>A / c.2101_2102delGA】. His mother’s TCIRG1 gene
genotype is【c.2101_2102delGA / WT】and father’s is【c.1213 G>A / WT】. The
CLCN7 gene genotype is【WT / WT】. The result of genetic analysis is compatible
with clinical diagnosis.
Conclusions: Prompt and precise diagnosis of ARO is indispensable for the early
treatment and genetic counseling . Our cases demonstrated the genetic analysis by
coupling DHPLC and HRM method as the first-line screening strategy. By these
modalities, we can confirm the diagnosis by genetic study and let genetic counseling
and prenatal screening of the sibling possible.
22
Vaccine Related ITP in Early Childhood: Experience of a Medical Center During
Past 20 Years
幼兒在疫苗注射後發生免疫性血小板過低症:一個醫學中心在過去二十年的經驗
Yuh-Lin Hsieh, Lon-Hwang Lin
Department of Pediatrics,Cathay General Hospital- Taipei
謝玉林、林隆煌
台北國泰醫院小兒科
Background: Vaccine related ITP through 9 yrs experience of a medical center in
Taiwan had been analyzed last year in this scientific meeting. Over diagnosis of
vaccine related Evans syndrome in this paper was questioned by senior hematologists.
After extending to 20 yrs retrospective chart review, we have different results.
Methods: Since Jan. 1989 till Dec. 2008, through chart review, all ITP children below
3 yrs old are studied.
Results: Among 20 cases with ITP, 13 cases were related to vaccine and 7 cases were
not related to vaccine-the same incidence as reported last yr. Five out of these 13
cases also had marked drop of hemoglobin without bleeding, possibly assumed as
Evans syndrome, which was reported last yr as 6 out of 7 cases-too high incidence.
Among these 13 cases: 5 cases were after 2nd dose HBV vaccine, 3 cases were after
1st dose DTPa contained
Conclusions: All but one case were treated smoothly with IVIG. The only one case
was treated smoothly with steroid. IVIG tx resulted in delayed subsequent vaccination
for at least 6 months, which changed the normal schedule a lot. Prospective
island-wide randomized tx trial using IVIG or steroid is needed.
23
Cyclic Vomiting Syndrome and Migraine in Children: Experience in One
Medical Center
兒童循環性嘔吐及偏頭痛: 一醫學中心之經驗
Yi-Pei Lin, Wen-Chin Weng, Yen-Hsuan Ni, Pi-Chuan Fan, Wang-Tso Lee
Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
林宜霈、翁妏謹、倪衍玄、范碧娟、李旺祚
國立台灣大學醫學院附設醫院小兒部
Background: Cyclic vomiting syndrome (CVS) is an episodic nausea and vomiting
disorder and commonly considered a precursor of migraine or migraine equivalent.
We retrospectively investigated the connection between clinical manifestation of CVS
and risk of migraine development in children.
Methods: 49 patients with the diagnosis of CVS in Taiwan with the onset age before
18 from 1976 to 2006 were reviewed retrospectively. 35 cases were included based on
Rome III criteria finally. Clinical evaluations included age of onset, sex, family
history, symptoms and duration, frequency, trigger events, electroencephalogram,
treatment and response. Development of migraine was asked by telephone visit in
October, 2008. We compared the correlation between different clinical patterns and
risk of migraine development using Pearson Chi-square, Two-sample t Wilcoxon
rank-sum test (STATA Version 10.0). Significance level was set at p < 0.05.
Results: Total 35 children (17 males and 18 females) were enrolled in the present
study. The age of onset ranged from 2 to 17 years (mean age: 6.8 years). The
frequency of attack ranged from once to 36 times per year (mean: 8.2 times). Duration
of symptoms ranged from one day to 45 days (mean: 5.9 days). We assessed the
migraine development in 20 children. Of these, 7 subsequently developed typical
migraine symptoms and the other 13 didn’t develop headache or migraine. We found
younger onset age in migraine-positive subgroup (11.7 + 3.3 years) compare with
migraine negative subgroup (16.8 + 3.3 years) (p: 0.004). Headache during CVS
attack is more evident in migraine-positive subgroup (2/7 cases of migraine-positive
and 0/13 cases of migraine-negative subgroup) (p: 0.042). There were no significant
differences in other clinical patterns with migraine development.
Conclusions: Although in limited cases, we found younger onset age and headache
during CVS attacks may indicate an increased risk of migraine development in rest of
life.
24
Lidocaine in the Treatment of Refractory Status Epilepticus in Children
Lidocaine 在兒童頑固型癲癇的治療
Jainn-Jim Lin1,2, Kuang-Lin Lin1, Huei-Shyong Wang1, Shao-Hsuan Hsia2,
Chang-Teng Wu2
Jainn-Jim Lin1,2, Kuang-Lin Lin1, Huei-Shyong Wang1, Shao-Hsuan Hsia2,
Chang-Teng Wu2 From 1Division of Pediatric Neurology, 2Divisions of Pediatric
Critical Care and Emergency Medicine, Chang Gung Children’s Hospital and Chang
Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan,
Taiwan
林建志 1,2、林光麟 1、王煇雄 1、夏紹軒 2、吳昌騰 2
林口長庚 兒童醫學中心 兒童神經內科 1 兒童加護科 2
Background: Status epilepticus (SE) is one of the most common neurologic
emergencies in children. Refractory SE (RSE) is most often symptomatic of an acute
neurologic condition. Treatment for RSE is difficult, usually requiring intensive
support of vital functions. Here we report an analysis of lidocaine in the treatment of
refractory status epilepticus in children.
Methods: We retrospectively reviewed cases of RSE treated in the pediatric intensive
care unit, between Jaunary 2001 and December 2008. The clinical characteristics were
systemically assessed. Burst suppression coma was induced by high-dose suppressive
therapy consisting of midazolam, propofol infusion, lidocaine. 24hrs EEG monitor
was performed in each patient. The goal of treatment was to achieve complete clinical
seizure control or burst-suppression pattern on EEG, aiming for an interburst interval
of >5 s. Brain MRI was followed after stable condition.
Results: There were 23 children with RSE. Five patients (2 girls and 3 boys), aged
6year-1 month to 15 year- 3months. The major clinical symptoms included fever
(100%), altered level of consciousness (100%) and upper respiratory symptoms (80%).
Initial EEG revealed multifocal with secondary generalized epileptiform
discharge(100%). All patient were poor responsed to multiple high dose suppressive
drugs except lidocaine. The dosage of lidocaine to cease seizure was ranged from 4 to
8 mg/kg/hr. All patients were intubated and 4 received inotropic agent. The time of
follow-up for this study was 4 months to 51 months. One died , 4 developed epilepsy
and/or neurologic deficits, and none returned to baseline. All survivors were
discharged on multiple antiepileptic medications.
Conclusions: Lidocaine seems to be useful for the management of CSE as a
rapid-acting anticonvulsant, particularly in patients with CSE due to infections. But
further studies with larger number of patients are needed.
25
Electroencephalogram Evaluation for cChildren with Headache in Pediatric
Outpatient Clinics
小兒科門診頭痛病人的腦波評估
Ai-Tyng Lim1, Hung-Tsai Liao, Ming-Lan Tsai2, Kun-Long Hung1
Department of Pediatrics, Cathay General Hospital, Taipei, Taiwan1 Department of
Pediatrics,Cheng Hsin rehabilitation medical center, Taiwan 2
林愛婷 1、廖宏才、蔡明蘭 2、洪焜隆 1
財團法人國泰綜合醫院小兒科 1, 財團法人振奮復健醫學中心小兒科 2
Background: Headache is one of the most challenging symptom in child neurological
practice. Most of the cause and type for headaches can be determined by a careful
history supplemented by a general and neurological examination. However, in the era
of managed care, lack of literature supports the utility of the electrophysiological tests
such as electroencephalography as an effective screening tool for headache.
Methods: We performed a retrospective medical record review of 594 children aged
< 18years with the diagnosis of headache or migraine visiting in our pediatric
outpatient clinic over an almost 2-year period (2007/03-2008/12). EEGs were
performed in 143 children. Among them, 23 children had repeated EEG. Besides, 24
children underwent brain CT and 7 children had brain MRI scan.
Results: In this retrospective survey, 294 (49.5%) children are male and 300 (50.5%)
children are female. The average age is 12.2 year old. In these 166 EEGs, abnormal
findings were found in 36 (21.9%) EEG. The common finding in these 36 abnormal
EEG were focal spikes (83.3%), secondary generalization (11.1%), slow wave
(13.9%), benign Rolandic spikes (2.8%) and sharp wave (2.8%). Two children had
normal EEG in the first examination but follow up EEG showed abnormal finding
with spikes. One of them developed epilepsy and showed good response to
antiepileptic drug. The CT showed two (8.3%) cases with arachnoid cyst, two (8.3%)
cases with megacistern magna and one (4.2%) with bilateral globus pallidus
calcification. Among seven children who underwent MR, only one(14.2%) revealed
abnormal finding with bilateral basal ganglia lesion.
Conclusions: We concluded that EEG is not significant in routine evaluation of
patients with headache, but may be useful in patients with unusual symptoms
suggesting epilepsy or migraine. However, it should be indicated in patients with an
abrupt onset of headache or migraine followed by neurological signs. The main
advantages of the EEG are noninvasiveness, accessibility and ability to repeat the test
if needed. Additional neuroimaging may be considered in some cases with abnormal
neurological examination.
26
Developmental Status of Preschool Children in Chang-Hwa County
彰化縣幼托園所發展遲緩兒童現況
Shoou-Tao Hsu, Ming-Yuh Chang1, Jen-Sen Lin2, Yen-Po Yeh3
Dr Hsu`s Clinics , Chang-Hwa Christian Hospital (1), Southern Taiwan University of
Technology (2), Chang-Hwa County Public Health Bureau (3)
許守道、張明裕 1、林振盛 2、葉彥伯 3
許小兒科診所 , 彰化基督教醫院(1) , 南台科技大學 (2) , 彰化縣衛生局(3)
Background: Early identification and intervention provides the most effective
therapy towards a successful recovery for children with developmental delay.
Preschools would be an excellent candidate for conducting group developmental
screening studies. This is the first report of a county wide group developmental
screening test within preschools in Taiwan.
Methods: 33 pediatric practitioners collaborated with 222 preschools in Chang-Hwa
county to conduct a group developmental screening study on 9022 children between
the age of 3 ~ 6. Individuals identified with developmental delay are either classified
as “abnormal” (failed more than 2 test items) or “questionable”, (failed only 1 test
item). Abnormal individuals are referred to the Chang-hwa Christian Hospital for
confirmation of developmental delay. All questionable individuals were re-screened
after one year.
Results: From the first round of screening, 1243 (13.8%) individuals were classified
as questionable and 238 (2.6%) individuals were classified as abnormal.
Characteristics associated with the abnormal group are: male, having a non-Chinese
speaking mother, residing in rural area, and reduced body weight and height.
Combination of having a non-Chinese speaking mother with reduced body weight and
height will increase the likelihood of being classified as abnormal by over 8 folds. Out
of 238 individuals in the abnormal group, 104 individuals were subjected to a
developmental delay assessment test and 97 (93.3%) were confirmed . All 1160
individuals in the questionable group were re-screened after one year and 74 (6.4%)
individuals were added to the abnormal group. A combined total of 312 (3.5%)
individuals were classified as abnormal for developmental delay from the first round
and the one year follow up screening.
Conclusions: A total of 9022 individuals in Chang-hwa county preschools were
tested by a group developmental screening test during 2007 and 2008. 93.3% of the
abnormal group that were subjected to a medical center assessment had confirmed
developmental delay and set the prevalence rate of developmental delay in preschools
at 1.1%. Surveillance of the questionable group added 74 individuals to the abnormal
group and increased the prevalence rate of developmental delay in Taiwan preschools
to 3.5% by screening.
27
Health-related Quality of Life of School-Age Children with Epilepsy in Central
Taiwan
中部地區癲癇學童健康相關生活品質調查
Ya-Ling Teng1, Inn-Chi Lee2,3, Shwn-Jen Lee4
Department of Occupational Therapy, Chung-Shan Medical University 1; Department
of Pediatrics, Division of Pediatric Neurology, Chung-Shan Medical University
Hospital 2; Institute of Medicine of Chung-Shan Medical University 3; Department of
Physical Therapy and Assistive Technology, National Yang-Ming University 4
鄧雅凌 1、李英齊 2,3、李淑貞 4
中山醫學大學職能治療學系 1 ; 中山醫學大學附設醫院小兒部小兒神經科 2; 中
山醫學大學醫學系 3; 國立陽明大學物理治療既輔具科技學系 4
Background: Epilepsy is one of the most prevalent pediatric neurological conditions
which is associated with poor psychosocial outcomes of children. It also presents
challenges for the parents and families that in turn influences development and
maintenance of psychosocial well-being of school-age children. The purpose of this
study was to compare health-related quality of life (HRQOL) between children’s and
parental perceptions, as well as to explore factors associated with HRQOL in children
with epilepsy.
Methods: Forty-seven children aged 7 to 18 years old with epilepsy, either active or
in remission, and fifty-nine parents having epileptic children were recruited from a
medical center in central Taiwan. Ronene’s Healthy- Related Quality of Life
Questionnaire-Taiwanese Version was self-administered by children, while parents
completed the proxy scale independently. Demographic as well as medical data were
also collected.
Results: Significant and moderate correlations were found in interpersonal and
intrapersonal domains between children’s and parental perceptions. However,
significant differences were found in the domain concerning present worries between
children and parental perceptions. In addition, possession of handicap certificates,
number of antiepileptic drugs（AEDs）taken, and family income were inversely
correlated with HRQOL in children with epilepsy. Those who possessed handicap
certificates, or took more than one AED, and families with lower income scored
poorer than their counter groups.
Conclusions: Parental perceptions did reflect children’s HRQOL at a certain level,
especially in interpersonal/social and intrapersonal/emotion domains that deals with
easily recognizable issues by others. However, parents tended to underestimate
children’s unspoken, underlying concerns of impacts on current life brought about by
Epilepsy. The side effects of multiple AEDs regimen and degrees of functional
impairment outweighed severity of epilepsy itself, and were associated with poor
HRQOL. Finally, family income may reflect substantial resources and supports
received by the family, and were associated with potential reinforcement of HRQOL.
28
Is there phenotypic dosage effect in patient compound heterozygous for
FSHD-sized 4q35 alleles?
在顏面肩胛上腕型肌肉失養症是否存在 Dosage effect ?
Wen-Chen Liang1,2, Kanako Goto2, Yukiko K Hayashi2, Mana Leung1, Ichizo
Nishino2, Yuh-Jyh Jong1
Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung,
Taiwan1; Department of Neuromuscular Research, National Institute of Neuroscience,
NCNP, Tokyo, Japan2
梁文貞 1,2、後籐加奈子 2、林由起子 2、梁曼妮 1、西野一三 2、鐘育志 1
高雄醫學大學醫學院附設醫院小兒部 1; 日本國立精神神經中心神經研究所疾病
研究第一部 2
Background: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal
dominant muscular disorder, associated with 4qA polymorphism and the deletion of
3.3-kb D4Z4 tandem repeats on chromosome 4q35. Herein, we report a Taiwanese
FSHD family, including three patients harboring two truncated alleles, and we
compare the clinical features between patients with one and two disease-related
truncated alleles to understand if there is dosage effect correlated to total D4Z4 repeat
number.
Methods: All clinical materials were obtained with informed consent. A total of 14
family members were examined. Genomic DNA was extracted from peripheral blood
lymphocytes with a standard technique. Southern blot analysis using the probe
p13E-11 and the specific probe for 4qA were performed. Clinical manifestations were
dissected for all 14 individuals and muscle CT was done in 11.
Results: Three patients were compound heterozygous condition carrying 24/27kb
EcoRI fragments with 4qA polymorphism. The 24kb fragment is inherited from
paternal side and 27kb one is from maternal side. Six of 14 have 24kb EcoRI
fragment and 5 carry 27kb fragment. From clinical point of view, younger generation
and younger siblings of the same generation tended to show more severe features,
suggesting anticipation. However, there is no significant difference in either muscle
involvement or clinical severity in patients with compound heterozygosity compared
with heterozygosity.
Conclusions: There is no phenotypic dosage effect correlated to total D4Z4 repeat
number in this FSHD family, raising the possibility that epigenetic effect may
influence the phenotype more than total number of D4Z4 repeat in FSHD.
29
FOXL2 mutations in Taiwanese patients with
blepharophimosis-ptosis-epicanthus inversus syndrome
台灣先天性家族性瞼口狹小症之 FOXL2 基因變異
I-Ching Chou1, Wei-Der Lin2, Ni-Chung Lee3, Chung-Shing Wang1, Huang-Tsung
Kuo1, Chang-Hai Tsai1, Shuan-Pei Lin4, Wuh-Liang Hwu3 ;Mei-Chyn Chao5, Fuu-Jen
Tsai1,2
Children’s Medical Center, China Medical University Hospital1;Department of
Medical Genetics, China Medical University Hospital2;Department of Medical
Genetics, National Taiwan University Hospital3;Departments of Pediatrics and
Medical Research, Mackay Memorial Hospital4;Department of Pediatrics, Division of
Genetics, Endocrinology and Metabolism, Kaohsiung Medical University Hospital5
周宜卿 1、林瑋德 2、李妮鐘 3、王仲興 1、郭煌宗 1、蔡長海 1、林炫沛 4、趙美琴
5
、胡務亮 3、蔡輔仁 1,2
中國醫藥大學附設醫院 兒童醫學中心 1;中國醫藥大學附設醫院基因醫學部 2;台
大醫學院附設醫院 基因醫學部 3;台北馬偕紀念醫院小兒部 4;高雄醫學大學附設
醫院 小兒科部 5
Background: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an
autosomal dominant disorder of craniofacial development. Most patients had
microcephaly, developmental delay and mental retardation. It’s a rare disorder, and a
subset case is associated with female infertility. Recent evidence has suggested that
BPES are caused by mutations in FOXL2 gene, located at 3q23. This study’s purpose
is to identify mutations in FOXL2 of Taiwanese patients with BPES.
Methods: The karyotype and genomic DNA was prepared from leucocytes of
peripheral venous blood of the study subjects. The coding region sequence of FOXL2
was analyzed by cycle and cloning sequencing.
Results: The karyotypes of these patients did not show significant variation,
especially on 3q23 region. Five mutations in FOXL2 were identified in six families,
including three mutations of c.855-871dup (17-bp insertion), and two mutations of
c.384G>A (TGG > TGA). Of the five, c.384G>A was novel and would result in
missense changes of the encoded proteins, i.e., p.Trp128X. The c.384G>A was
detected in one family. The c.855-871dup mutation was found in the other families.
Conclusions: Our results expand the spectrum of FOXL2 mutations and confirm the
mutation in FOXL2. We identified one novel and one known mutations in FOXL2 of
six Taiwanese families with BPES. Although four families have not been detected
with mutation up to now, this does not necessarily exclude the possibility that other
mutation types exist in their FOXL2 gene, such as inversions, translocations,
micro-deletion, and mutations within the promoter region. Further studies will be
required to determine the potential role of this locus in BPES.
30
SMN2 Gene Dosages in Normals, Carriers and Patients with Spinal Muscular
Atrophy
SMN2 基因在正常人、脊髓肌肉萎縮症患者及帶因者之基因劑量
Tai-Heng Chen1,2, Chun-Chi Wang3, Shou-Mei Wu3,4, Yi-Ching Chen2, Rei-Cheng
Yang1, Yuh-Jyh Jong1,2
Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung
Medical University, Kaohsiung, Taiwan1; Gradudate Institute of Medicine, College of
Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan2; School of Pharmacy,
College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan3;
Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung
Medical University, Kaohsiung, Taiwan4
陳泰亨1,2、王俊棋3、吳秀梅3,4、陳怡靜2、楊瑞成1、鐘育志1,2
高雄醫學大學附設醫院 小兒科部1; 高雄醫學大學 醫學院 醫學研究所2; 高雄
醫學大學 藥學院 藥學系3; 高雄醫學大學 藥學院 香妝品學系4
Background: Spinal muscular atrophy (SMA) is characterized by degeneration of the
anterior horn cells of the spinal cord and classified into three groups as type I (severe),
type II (intermediate) and type III (mild) based on age of onset and clinical severity.
Survival motor neuron gene 1 (SMN1) is homozygously deleted in >95% of SMA
patients. A nearly identical SMN1 copy gene, SMN2, is almost retained in all SMA
patients and regarded as a SMA modifying gene. In this study, we analyze the SMN2
gene dosages in normals, carriers and SMA patients.
Methods: To evaluate the SMN2 gene dosages, capillary electrophoresis was used for
quantifying SMN1 and SMN2 copy numbers in 88 Taiwanese SMA patients (8 type I,
42 type II and 38 type III), 105 parents of SMA patients (obligatory carriers) and 111
normal individuals.
Results: The average copy number of SMN2 gene was significantly higher in SMA
patients than carriers and controls (3.1±0.7, 2.3±0.7 and 1.5±0.6, respectively, p <
0.05). In SMA carriers, there was a significant trend for parents of SMA type I
patients to have fewer SMN2 copies compared to those of type II-III patients (1.9±0.2
vs. 2.4±0.1, p < 0.05). Moreover, the SMN2 copy number in type II–III SMA patients
is higher than type I SMA patients (3.1±0.1 vs. 2.4±0.2, p < 0.05).
Conclusions: We demonstrate the gene conversion from SMN1 to SMN2 among
normal population, SMA patients and carriers and an inverse correlation between the
SMN2 copy number and clinical severity. However, 37.5% of type I and 52.5 % of
type II-III SMA patients have 3 SMN2 copy numbers, which suggests SMN2 alleles
may not be functionally equivalent among SMA patients. We propose other genetic
background, such as splicing mechanisms of the SMN2 gene or another modifying
gene(s) may influence SMA severity.
31
The Association of Plasma Copper and Ceruloplasmin Levels with Clinical
Symptoms in Children of Tic Disorders
抽搐症兒童血中銅離子和轉銅素濃度與臨床症狀之相關性
Jung-Chieh Du1, Ting-Fang Chiu1, Kun-Mei Lee1, Hsin-Lin Wu1, Yu-Chuan Lin1,
Ya-Chi Yang1, Hsu-Yeh Shu1, Chung-Shu Sun1, Betau Hwang1,2
1
Department of Pediatrics, Taipei City Hospital, Zhongxiao Branch, Taipei, Taiwan
2
National Yang-Ming University, Taipei, Taiwan
杜戎玨 1、邱婷芳 1、李坤美 1、吳幸霖 1、林玉娟 1、楊雅淇 1、許淑埜 1、孫中淑
1
、黃碧桃 1,2
1
台北市立聯合醫院忠孝院區小兒科 2 國立陽明大學
Background: Abnormalities of copper metabolism in patients with Tourette
syndrome had been reported. The pathogenesis of tic disorders or Tourette syndrome
is not well elucidated but hyperactivity of dopaminergic system is thought to be the
major mechanism. Because copper and ceruloplasmin serve as components of several
enzymes linked to dopamine synthesis, a study to investigate the association of
plasma copper and ceruloplasmin levels with clinical symptoms in children of tic
disorders was conducted.
Methods: Total 42 children (M/F=39/3) aged from 3~14 years (mean ± SD: 7.7±2.2
years) with tic disorders were recruited in this study, including 28 children with
Tourette syndrome(TS) and 14 children with transient tic disorders (TTD). These
children''s tic symptoms were evaluated by Yale Global Tic Severity Scale (YGTSS),
with total scores, motor scores, phonic scores and impairment scores. The plasma
level of copper, ceruloplasmin, and anti-streptolysin O (ASLO) titer were detected
and analyzed in all 42 children.
Results: The mean copper level was 1106.9± 33.11 ug/L(s.e.m) and ceruloplasmin
level was 23.5±0.62 mg/dL(s.e.m) in all 42 children. Copper level was below 800ug/L
in 3 and was higher than 1500ug/L in one child. All children''s ceruloplasmin levels
were within normal limits and total 13 (31%) children had abnormally higher ASLO
titers. Copper levels were negatively correlated with patients'' age (r=-0.37, p=0.02)
and motor scores (r=-0.36, p=0.02), but not related to the total scores or phonic scores.
Ceruloplasmin levels had negative correlation with patients'' age (r=-0.31, p=0.04)
and onset age of tic symptoms (r=-0.37, p=0.02) but no association with YGTSS
scores. ASLO titers were not correlated with any factors. There were significant
differences in onset age (p=0.002), total scores (p=0.000), motor scores (p=0.000),
vocal scores (p=0.001) as well as impairment scores (p=0.004) between TS and TTD
groups. However, the mean copper levels, ceruloplasmin levels and ASLO titers were
not significantly different between the two groups. In TS group, only motor tic
frequency was negatively correlated with copper levels (r= -0.40, p=0.008) as well as
ceruloplasmin levels (r=-0.38, p=0.014). But in TTD group, however, no significant
correlation was found between YGTSS scores with copper and ceruloplasmina levels.
Conclusions: our study demonstrated that plasma copper levels were associated with
motor tic symptoms in children with tic disorders, especially in those with TS. Further
studies are needed to elucidate the role of copper in the pathogenesis of tic disorder.
32
Effect of Heat Shock Pretreatment on the Permeability of Phenytoin in Rat Brain
熱休克前處置對大白鼠腦內 Phenytoin 通透性的影響
Lung-Chang Lin, Ting-Jun Chen1, Rei-Cheng Yang
Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung
Medical University; Departmet of Physiology1, Graduate Institute of Physiology and
Molecular Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
林龍昌、陳亭君 1、楊瑞成
高雄醫學大學附設醫院 小兒部; 高雄醫學大學 生理及分子醫學研究所 1
Background: Clinically, fever is a major trigger factor to induce a seizure attack in
children with epilepsy, even though the level of anticonvulsant in plasma is within
therapeutic range. Fever induces the heat shock response which produces heat shock
proteins (HSPs). In vivo microdialysis experiments have shown that phenytoin is a
substrate of P-glycoprotein or multi-drug resistance protein 2 in rats. They export
drugs back into the blood before these drugs enter the brain parenchyma. In this study,
we proposed that heat shock pretreatment might alter the concentration of phenytoin
in the brain after injection of phenytoin.
Methods: Adult Sprague-Dawley rats (300～350g) were used as the experimental
animals. Phenytoin concentrations of brain and plasma were assayed by a high
performance liquid chromatography (HPLC) with UV light detection and divided into
heat and non-heat group. Heat shock was achieved by an electric heating pad. Western
blot analysis was used for evaluating the heat shock protein 72 (Hsp72), occludin,
P-glycoprotein and multi-drug resistance protein 2.
Results: The result showed that Hsp72 was significantly increased in the brain after
heat shock pretreatment. Blood concentration of phenytoin was not different between
heat-shocked and non-heated rats. Heat shock pretreatment could reduce the
concentration of phenytoin in the brain associated with decrease of multi-drug
resistance protein 2. But there was no change in the contents of occludin and
P-glycoprotein.
Conclusions: We suggested that heat shock pretreatment could decrease the
concentration of phenytoin in the brain which might act through the multi-drug
resistance protein 2 pathway, but not P-glycoprotein.
33
ETFDH Mutations, CoQ10 Levels, and Respiratory Chain Activities in Patients
with Riboflavin-responsive Multiple Acyl-CoA Dehydrogenase Deficiency
在 Riboflavin-responsive Multiple Acyl-CoA Dehydrogenase Deficiency 病人對於
ETFDH 基因突變, CoQ10 及粒線體呼吸鏈酵素活性的分析
Wen-Chen Liang{1,6}, Aya Ohkuma{1}, Yukiko K. Hayashi{1}, Luis Carlos López{2},
Michio Hirano{2}, Ikuya Nonaka{1}, Satoru Noguchi{1}, Liang-Hui Chen{3}, Ichizo
Nishino{1}, Yuh-Jyh Jong{4,5,6}
Department of Neuromuscular Research, National Institute of Neuroscience, National
Center of Neurology and Psychiatry (NCNP), Japan1; Department of Neurology,
Columbia University Medical Center, New York, NY, U.S.A.2; Department of
Pediatrics, Taichung Veterans General Hospital, Taichung3; Graduate Institute of
Medicine, Kaohsiung Medical University 4and Departments of Laboratory Medicine
and Pediatrics, Kaohsiung Medical University Hospital5,6, Kaohsiung, Taiwan.
梁文貞{1,6}、大熊彩{1}、林由起子{1}、埜中征哉{1}、野口悟{1}、陳良惠{3}、西野
一三{1}、鐘育志{4,5,6}
國立神經精神中心 神經研究所 疾病研究第一部, 日本 1; 哥倫比亞大學醫學中
心 神經內科, 美國 2; 台中榮民總醫院 小兒科, 台中 3; 高雄醫學大學 醫學研究
所 4; 高雄醫學大學附設醫院 醫學檢驗部 及 小兒科部 5,6, 高雄, 臺灣
Background: Multiple acyl-coenzyme dehydrogenase deficiency (MADD), or
glutaric aciduria type II, is caused by defects in electron transfer flavoprotein or
ETF-ubiquinone oxidoreductase (ETF:QO). This disorder can show neonatal onset
form with or without congenital anomalies or later-onset milder form. Decreased
respiratory chain activities have been reported in MADD patients. Recently, riboflavin
treatment has been known to be effective in MADD patients with mutations in the
gene for ETF:QO (ETFDH).
Methods: Four patients in 3 Taiwanese families with later-onset MADD were
analyzed. Clinical information was reviewed according to medical records. Mutation
screening of ETFDH and haplotype analysis were done by using genomic DNA.
Respiratory chain activities were determined spectrophotometrically and CoQ10 level
was measured by high performance liquid chromatography.
Results: Three novel ETFDH mutations were identified in four patients and all
harbored the p.A84T mutation. Muscle CoQ10 levels and respiratory chain activities
measured in two patients were normal. Three patients improved on riboflavin together
with carnitine.
Conclusions: Our results show that p.A8T mutation in ETFDH may be due to a
founder in Taiwan, and not all MADD patients have CoQ10 deficiency. Based upon
our data, riboflavin and carnitine may be the first-line treatment for MADD.
34
National Survey of Invasive Pneumococcal Diseases in Taiwan under Partial
PCV7 Vaccination in 2007: High Invasive Potential of Serotype 19A in Children
2007 年台灣侵襲性肺炎雙球菌的調查:血清型 19A 於孩童的高侵襲性
Yu-Chia Hsieh, Pen-Yi Lin, Cheng-Hsun Chiu, Yhu-Chering Huang, 2007
pneumococcal study group, Tzou-Yien Lin
Division of Infectious Diseases, Chang Gung Children’s Hospital, Chang Gung
University College of Medicine
謝育嘉、林本一、邱政洵、黃玉成、2007 肺炎鏈球菌團隊、林奏延
林口長庚兒童醫學中心感染科
Background: An active, nationwide, population-based laboratory surveillance study
was conducted to evaluate the epidemiologic features of invasive pneumococcal
diseases in 2007 in Taiwan where 20% coverage was achieved by 7-valent
pneumococcal conjugate vaccine (PCV7) among children.
Methods: We examined data on invasive pneumococcal disease in patients identified
in a program supported by the Centers for Disease Control, Taiwan from January 1,
2007 to December 31, 2007. At the same time, nasopharyngeal colonization of
Streptococcus pneumoniae were studied among 1147 children aged ≦ 5 years.
Results: During the transition period, a total of 521 cases of IPD were reported. The
overall incidence was highest among children aged 2 to 4 years (15.6 /100000).
Among this age group, nonsusceptibility to ceftriaxone was extremely high (76.4%
for meningitis criteria, and 21.3% for nonmeningitis criteria). Serotype 19A
significantly caused invasive diseases and ranked as the fourth serotype that causing
invasive diseases among children aged between 2 to 4 years, which had never been
reported previously in Taiwan. Comparing isolates from nasopharyngeal colonization
among children aged ≦ 5 years, serotype 14 and 19A had highest invasive potential.
Patients aged ≧ 65 years and malignancy were independent risk factors for mortality
(OR,3.4; 95% CI, 2.0-5.7 for elderly; OR 2.3; 95% CI, 1.3-4.0 for malignancy). Cases
with diabetes mellitus significantly predisposed to serotype 3 infection (OR, 2.5; 95%
CI, 1.2-5.0).
Conclusions: PCV7 should offer children widely in order to decrease pneumococcal
disease burdens. In the future, a pneumococcal vaccine broadening the serotype
coverage is needed.
35
Longitudinal Follow up of Children Born to Human Immunodeficiency Virus
Infected Mother in Southern Taiwan: the Impact of Prophylaxis Antiretroviral
Therapy on Vertical Transmission
南台灣愛滋病毒感染母親生產的兒童長期追踪:預防性抗愛滋病毒藥物使用對垂
直傳染的影響
Mu-Han Yang, Tzong-Shiann Ho, Ching-Fen Shen, Shih-Min Wang1, Ching-Chuan
Liu
Departments of Pediatrics and Emergency Medicine1, National Cheng Kung
University & Hospital, Tainan, Taiwan.
楊慕涵、何宗憲、沈靜芬、王世敏 1、劉清泉
國立成功大學醫學院附設醫院小兒部、急診部 1
Background: Mother-to-child transmission (MTCT) accounts for major human
immunodeficiency virus (HIV) infections among children. Taiwan government
authority had taken universal interventions including antiretroviral prophylaxis,
elective cesarean delivery and avoidance of breastfeeding to prevent perinatal HIV
infection since 2006. The aim of this study is to evaluate the clinical course of these
infants born to HIV-infected mother and the effect of antiretroviral prophylaxis.
Methods: Children born to HIV-infected mothers between 1995 and 2008 followed
up at National Cheng Kung University Hospital were enrolled. The children who
received prophylactic antiretroviral therapy (ART), cesarean section and bottle
feeding were categorized as intervention group. Demographic data, clinical feature
and laboratory characteristics of the children and maternal virologic and immunologic
data were retracted from medical records.
Results: Totally 15 children (intervention= 8; non-intervention= 7) were enrolled. In
the intervention group, 6 mothers received ART during pregnancy and 4 among them
also received intravenous ziduvidine during labor. Only 4 of them had undetectable
viral load before delivery. All 8 infants within the intervention group received
postnatal oral ziduvidine for 6 weeks. All children with intervention had undetectable
viral load at birth but positive anti-HIV Ab. Six among them are categorized as
definitely uninfected with HIV, while two remains indeterminate HIV infection. HIV
antibodies disappeared between the age of 6 and 18 months. There were 7 children
without interventions due to delayed diagnosis of maternal HIV infection, and all
were born from vaginal delivery and breastfed. Three of 7 children (42.8%) without
interventions were confirmed to be HIV-1-infected and 2 of them progressed into
acquired immunodeficiency syndrome stage with average CD4+ T-lymphocyte count
of 50 and 180 cells/μL, respectively.
Conclusions: Early identification of HIV infection in pregnant women and
appropriate interventions effectively reduces the risk of mother-to-child transmission.
36
The Treatment Provided to Tuberculosis Contacts Aged 12 Years and Younger --Preliminary Report of The Program of Directly Observed Preventive Therapy
小於等於 12 歲之結核病接觸者所接受到的治療---潛伏性結核病感染都治關懷治
療計劃之初步報告
Pei-Chun Chan, Bao-Yun Lu, Kwei-Feng Wang, Chin-Hui Yang
Center for Disease Control, Taipei, Taiwan
詹珮君、呂寶雲、王貴鳳、楊靖慧
衛生署疾病管制局
Background: Contact tracing program in Taiwan has been strengthened through
free-charge policy to all close contacts of confirmed tuberculosis (TB) cases since
2007, September. Latent TB infection (LTBI) Treatment has been provided to children
contacts aged 12 years or younger through directly observed preventive therapy
(DOPT) since 2008, April.
Methods: Contact aged 12 years and younger registered during April to September,
2008 were enrolled in the study. The data was obtained from the National Surveillance
Network of Communicable Disease (NSNCD), Centers for Disease Control, Taiwan.
Results: A total of 3037 children who were contacts of pulmonary TB were identified.
Their index cases were 47% smear positive, 79% culture positive, and 24% with
cavitary lung lesion. Thirty percent of the children were younger than 5 year-old, and
20% were 10 years and elder. Among 782 children (26%) with positive TST, 52%
received treatment. Among 2255 children (74%) with negative TST initially, only
11.8% received treatment. For those index cases with highest grade of infectivity,
children with negative TST initially had 77% reduced chance to receive prophylaxis
compared to those with positive TST (RR=0.23, 95% CI=0.17-0.31, p<0.0001). For
those younger than 5 year-old, the reduction decreased to 69% compared to 80% in
children aged 5 and elder. Overall, proportion of LTBI treatment correlated
significantly with contagious situation of index cases in both age groups (p=0.0023,
p=0.0068).
Conclusions: LTBI treatment or prophylaxis is generally recommended for all contact
children of pulmonary TB. In this study, treatment was successfully provided to half
of the children with positive TST in the first 6 months of the program. However,
prophylaxis provided to children with initial negative TST was still limited, even the
index cases were smear positive, and cavitary lung lesion. Contagious status of index
cases provided routinely in referral sheets may help physicians making clinical
judgment of providing care to contact children.
37
The Epidemiology and Clinical Characterizations of Invasive Haemophilus
Influenzae type b Diseases in Taiwan Children
探討台灣兒童侵襲性 b 型嗜血桿菌感染症的流行病學及臨床特徵
Hui-Chen Lin1, Yung-Chao Lei1, Sung-Hsi Wei1, Chien-Hui Lin1, Kun-Bin Wu2,
Tzung-Han Li2
Centers for Disease Control, Taiwan
林慧真 1、雷永兆 1、魏嵩璽 1、林千惠 1、巫坤彬 2、李宗翰 2
衛生署疾病管制局第七分局 ｛1｝ 衛生署疾病管制局第二組 ｛2｝
Background: Haemophilus influenzae type b (Hib) is an important cause of
childhood morbidity and mortality, especially in young children. The epidemiology
and characterizations of invasive Hib diseases in children and the impact of Hib
vaccination has not been studied well after its introduction to Taiwan in 1996.
Methods: We reviewed 293 reported cases (<18 years of age) with invasive Hib
diseases to Centers of Disease Control from the period between July1998 and
December 2007. Invasive Hib disease was defined as isolation of Hib from the
patients’ sterile specimens. Clinical information on cases was collected by chart
review.
Results: During the study period, a total of 233 confirmed cases of invasive Hib
diseases were identified. Male to female ratio was 1.9. The median age was 2 years
(range, 1 day to 18 years). Children less than two years of age accounted for 51% of
the cases. The annual incidence in children aged less five years also decreased from
2.82 /100,000 in 1999 to 0.55 cases /100,000 in 2007. The most common clinical
manifestations of invasive Hib diseases were pneumonia (97), meningitis (95),
bacteraemia without foci (22), cellulitis (13), septic arthritis (12), otitis media (11),
and epiglottitis (7). Nineteen patients had co-morbidities. Only three cases had been
vaccinated with Hib vaccines. Thirteen of 220 cases were dead, and the overall case
fatality was 6%. Among 207 survivors, 60 cases developed long-term sequelaes,
including auditory deficits, motor deficits, and seizures as the three most common
sequelaes.
Conclusions: In Taiwan, invasive Hib disease can cause significant morbidity and
mortality in children. In line with the increased uptake of Hib vaccination children,
the overall incidence of invasive Hib infections in children decreased gradually.
38
Long-term characteristics of nosocomial infection in a neonatal intensive care
unit
新生兒加護病房院內感染變化之長期特徵
Tzong-Shiann Ho, Shih-Min Wang1, Ching-Fen Shen, Chyi-Her Lin, Yuh-Jyh Lin,
Ching-Chuan Liu
Department of Pediatrics and Emergency Medicine1, National Cheng Kung University
Medical College and Hospital, Tainan, Taiwan.
何宗憲、王世敏 1、沈靜芬、林其和、林毓志、劉清泉
國立成功大學醫學院附設醫院小兒部，急診部 1
Background: Nosocomial infections in the neonatal intensive care unit (NICU) are
associated with significant risk of morbidity and mortality. Pathogens, primary source
of infections and antibiotic resistance in NICU are essential for developing
management strategies. This study is aimed to analyze the long-term characteristics of
nosocomial infection in a tertiary referring center in southern Taiwan.
Methods: Infants who were < 30 days of age, and had positive blood, CSF, urine or
tissue fluid cultures during hospitalization at NICU of National Cheng Kung
University Hospital from July, 1989 to June, 2008 were recruited.
Results: Totally 1417 organisms and episodes were identified during the study period.
Gram-positive organisms, Gram-negative organisms and fungi constituted 923
(65.1%), 358 (25.3%) and 136 (9.6%) of the pathogens. Among Gram-positives,
coagulase-negative Staphylococcus (51.5%), Staphylococcus aureus (34.8%) and
Enterococcus spp. (6.1%) were major pathogens. Twenty-seven percent of isolated
Staphylococcus aureus was oxacillin-resistant. As to the Gram-negatives, Klebsiella
pneumoniae (22%), Pseudomonas aeruginosa (21.8%), Escherichia. coli (16.7%) and
Enterobacter cloacae (16.7%) dominated. Besides, Candida albicans accounted for
half of the fungal infections. The most common source of infection was bloodstream
infection (55.8%), and 5.5% of them was catheter-related. Futhermore, skin and soft
tissue infections (27.7%) were also frequent.
Conclusions: Bloodstream and skin/soft tissue infection caused by commensal
species play important roles in the nosocomial infection in NICU. New measures
should be developed in response to the changing pattern in NICU.
39
Can We Predict Gastroenteritis Pathogen via Stool Character in Hospitalized
Children?
腸胃炎住院兒童糞便形態與病原體之關係
Lung Chang1, Nan-Chang Chiu1, Hsin Chi1, Fu-Yuan Huang1, Hung-Chang Lee1
Department of Pediatrics, Mackay Memorial Hospital, Taipei
張龍 1、邱南昌 1、紀鑫 1、黃富源 1、李宏昌 1
台北馬偕紀念醫院小兒科
Background: To answer the question: is the character of stool helpful in the
identification of gastroenteritis pathogen in hospitalized children?
Methods: The admitted pediatric patients (<18 year-old) with the diagnosis of
gastroenteritis from March 2008 to August 2008 were enrolled in this study. Detailed
clinical history and manifestations were taken from primary caregivers. The character
of stool was further analyzed for defecation frequency (<3, 3 to10,>10 times/day),
consistency (semi-solid, loose, watery), blood tinged or mucoid appearance, and color
(yellowish, yellow-greenish, greenish). Isolation of the specific bacterial enteric
pathogen or detection of viral antigen from the stool specimen was performed in all
patients, and these results were further correlated with the clinical and laboratory data.
Results: A total of 319 patients were enrolled. Stool cultures from 129 patients grew
specific bacteria pathogens, and rotavirus antigen was detected in 59 subjects. Mixed
infection of bacteria and rotavirus were found in 4 patients, but no pathogen was
identified from the stools in the other 135 patients; these patients were excluded from
further analysis. Therefore, 180 patients were divided into two groups: bacteria group
(125 patients) and Rotavirus group (55 patients). Rotavirus group was prone to suffer
from vomiting, watery stool, and shared similar symptoms with their family members
(p < 0.001). Greenish or yellow-greenish stool, with blood tinged or mucoid
appearance strongly suggested bacteria cause of gastroenteritis in children (p <
0.0001). A combination of greenish or yellow-greenish, blood tinged, and mucoid
stools showed a positive predictive value of 77% for bacterial infection. No statistical
difference in sex, age, fever, frequency of defecation or breast milk feeding was found
between the bacteria or rotavirus groups.
Conclusions: Our results demonstrate the importance of detailed clinical history in
diagnosing infectious gastroenteritis in children. Careful analysis of stool
characteristics aids in the prediction of pathogen in gastroenteritis.
40
Fecal Viral Excretion in Children Received Live Attenuated Oral Polio Vaccine
with Prior Inactivated Poliovirus Vaccination
先前己接種注射型小兒麻痺疫苗的兒童再次接種口服減毒小兒麻痺疫苗後其糞
便中病毒的排出
Ching-Fen Shen1, Tzong-Shiann Ho1, Huey-Pin Tsai2, Pin-Hwa Kuo2, Shih-Min
Wang3, Jen-Ren Wang4, Ching-Chuan Liu1
Department of Pediatrics1, National Cheng Kung University & Hospital; Department
of Pathology2, National Cheng Kung University & Hospital; Department of
Emergency Medicine3, National Cheng Kung University & Hospital; Department of
Medical Laboratory Science and Biotechnology4, National Cheng Kung University,
Tainan, Taiwan.
沈靜芬 1、何宗憲 1、蔡慧萍 2、郭品樺 2、王世敏 3、王貞仁 4、劉清泉 1
國立成功大學醫學院暨附設醫院小兒部 1, 病理部 2, 急診部 3, 國立成功大學醫學
院醫學檢驗生物技術學系 4
Background: In afraid of immigrant poliomyelitis, Taiwan health authority had
recommended universal OPV administration in children who only received
inactivated poliovirus vaccine (IPV) before to enhance herd immunity. The aim of this
study is to evaluate the viral excretion after sequential schedule of IPV and OPV and
the herb immunity induced by viral transmission to household contacts.
Methods: All children (< 2 years), who had already received at least two doses of
IPV but not OPV, visiting National Cheng Kung Hospital for the routine physical
examination were enrolled. Stool specimen or rectal swab was collected from vaccine
recipients along with their major caregiver and siblings for viral isolation before
taking OPV, and two and four weeks after OPV administration. Stool samples were
inoculated into Hep-2 and L20B cell culture for viral isolation.
Results: Totally 40 children were enrolled, with a mean age of 9.7 months (range
6.1~18.9 months). Before OPV administration, only one case (2.5%) had poliovirus
isolated from rectal swab. However, 15 from 30 (50%) and 8 from 27 (29.6%)
children had poliovirus isolated from stool two and four weeks after OPV
administration. The overall poliovirus shedding rate is 58.1% (18 from 31 children).
Stool from 33 major caregivers and 10 siblings were also collected for viral isolation
after OPV administration to the index case. Only one caregiver had poliovirus
detected two weeks, while another one had poliovirus detected four weeks later. There
was no poliovirus isolated from stool of all siblings within four weeks. The viral
transmission rate to caregiver and siblings was 6.1 % and 0 % respectively.
Conclusions: Although vaccine strain poliovirus was isolated from subjects received
OPV, the intrafamily transmission rate is low due to good sanitary condition and
personal hygiene of the community. The diminished effect of OPV on herd immunity
may serve as useful information to modify the current vaccination program.
41
Development of inhalational siRNA therapy in animal model to treat influenza
virus infection
利用動物模式評估微小干擾核糖核酸治療流行性感冒病毒感染
Pei-Lan Shao, Miao-Fen Chao, Chun-Yi Lu, Betty Hsieh-Wu, Luan-Yin Chang,
Chin-Yun Lee, Li-Min Huang
Department of Pediatrics, National Taiwan University Hospital
邵蓓嵐、趙妙芬、呂俊毅、伍安怡、張鑾英、李慶雲、黃立民
國立台灣大學醫學院附設醫院小兒部
Background: Influenza viruses cause major health threat both seasonally and
epidemically. Current intervention includes vaccination and antiviral agents. There are
drawbacks in both measures. We have developed a novel strategy using RNA
interference (RNAi) against influenza virus replication. The PA and PB2 genes
encoding transcriptase are the targets of RNAi. By transfecting plasmid vector
containing shRNAs or shRNAmir, replication of influenza A virus were shown to
successfully inhibited.
Methods: We aim to develop an inhalational administration of RNAi-based therapy.
The setup of aerosol delivery system used in mice model was accomplished. The
effect and safety in vivo application of inhalational siRNA therapy are investigated in
the mice model. We used C57BL/6 mice aged 6-10 week for experiments. Influenza A
viruses (H1N1 or H3N2) were intra-tracheal inoculated to each mouse at 105 PFU.
Gross and histopathological examination of lung tissue specimens at 0, 1, 2, 3, 4, 8
days post-inoculation (DPI) were performed.
Results: Grossly, severe hyperemia, consolidation, and interlobular edema were noted
at 8 DPI. Necrotizing bronchitis and severe interstitial and proliferative pneumonia
with alveolar hemorrhage were found in histopathological exam. After 8 days of
inoculation, only 20% of mice inoculated with influenza A viruses survived. After
establishing the influenza A virus infection mouse model, we use PARI BOY&reg; N
compressor to deliver aerosolized pDNA/PET complexes to mice. By recognizing the
expression of EGFP in the bronchial epithelium and pneumocytes, we assure this
inhalational method able to deliver aerosolized plasmid vectors into the respiratory
tract of mice.
Conclusions: In the next step, we use this system to evaluate the efficacy of RNAi
therapy against influenza infection. Toxicities to the other major organs are also
evaluated. The evaluation of RNAi therapy efficacy is ongoing. We believe this novel
strategy can be an auxiliary in the treatment of influenza virus infection
42
Inhibition of Human Metapneumovirus Protein Expression and Viral
Replication by RNA Interference Targeting Phosphoprotein
利用 siRNA 干擾磷蛋白質來抑制人類間質肺病毒之複製:
Sui-Ling Liao1,3, Shen-Hao Lai1,2,3, Xiaoyong Bao3, Antonieta Guerrerro-Plata3,
Chao-Hong3, Roberto P Garofalo3, Antonella Casola3
Department of Pediatrics, Keelung, Chang Gung Memorial Hospital 1; Division of
Pediatric Pulmonology, Chang Gung Children’s Hospital and Chang Gung University,
Taoyuan, Taiwan 2, Departments of Pediatrics, University of Texas Medical Branch,
Galveston, Texas 3
廖穗綾 1,3、賴申豪 1,2,3
長庚紀念醫院; 基隆院區兒科 1, 長庚兒童醫學中心 兒童胸腔科 2, 德洲大學醫
學分院兒科 3
Background: Human metapneumovirus (hMPV) is one of the major causes of airway
infections in young infants, causing bronchiolitis, croup, asthma exacerbation, and
even pneumonia.Despite clinical significance of hMPV, there are no vaccines,
chemotherapeutic agents, or specific antibodies currently available for hMPV
infections. We aim to design an effective antiviral agent using siRNA, and document
its effectivenss through in vitro studies.
Methods: Four varaints of siRNA targeting against viral phosphoprotein (P protein)or
a non-specific siRNA as control were introduced into A549 cells through
electropolation. Cells were infected with hMPV after overnight incubation.
Flowcytometry and fluorescence microscopy were used to detect viral antigen
expression. Viral titration was achieved by plaque assay. Semi-quantitative RT-PCR
was done to detect gene expression of viral P and N proteins. Protein expression of F
protein was analyzed by Western blot.
Results: Two siRNAs were effective in decreasing viral replication and viral antigen
expressions, mediating a gross cytoprotective effect on the target cell.
Semi-quantitative PCR showed the inhibition of siRNA to be specific against P
protein, as the gene expression of N protein remained intact. Viral F protein
expression has also decreased significantly in the effective siRNA group indicating
successful inhibition of virion assembly.
Conclusions: Our data suggests that, when properly designed, siRNAs targeting
against P protein can be a promising antiviral approach for hMPV infections, allowing
future develoepment of novel treatment for prevention of viral induced complications
in pediatric patients.
43
Identification of Novel Genes and Related Mechanisms Necessary for Salmonella
Resistance to Bile
沙門氏菌對抗膽汁殺菌之相關基因鑑定及其機轉的探討
Ming-Han Tsai1,2, Cheng-Hsun Chiu3,4, Yhu-Chering Huang3,4, Tzou-Yien Lin3,4
Department of Pediatrics, Chang Gung Memorial Hospital, Keelung, Taiwan 1 ;
Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan,
Taiwan 2 ; Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang
Gung Children''s Hospital, Taoyuan, Taiwan 3; College of Medicine, Chang Gung
University, Taoyuan, Taiwan 4
蔡明翰 1,2、邱政洵 3,4、黃玉成 3,4、林奏延 3,4
長庚紀念醫院基隆分院小兒科 1 ; 長庚大學臨床醫學研究所 2 ; 林口長庚兒童
醫院小兒感染科 3 ; 長庚大學醫學院 4
Background: Salmonella infection is an important public health problem and it lives
in the intestine. To survive in the intestine, it must endure environmental extremes,
including bile. Bile is made by the liver and secreted into the intestine to help the
digestion of fats. As a detergent, bile possesses potent antimicrobial activity. The
recognition of mechanisms about bile resistance of Salmonella may improve our
understandings in the pathogenesis of related antimicrobial resistance or the
development of carrier status.
Methods: Strains used in this study were Salmonella enterica serovar Typhimurium
(SL1344) and bile-sensitive SL1344 mutants were created by transposon mutagenesis.
Strains containing transposons were selected on LB-kanamycin plates and then
screened for a bile sensitive phenotype by plating onto bile-containing plates. Those
loss of growth on bile-containing plates were selected and then confirmed as
bile-sensitive mutants with quantitative ELISA reader. To further identify the loci of
disrupted genes, DNA sequencing of the transposon- chromosomal-DNA fusion
junctions of the mutants was performed.
Results: After screening 1035 mutants for loss of growth on LB broth-bile plates, 5
bile-sensitive mutants were identified and the disrupted genes were rfaP(2), rfbK(1),
dam(1) and tolC (1). The mutated genes rfaP and rfbK may result in rough
lipopolysaccharide (LPS), which lead to increase membrane access and then decrease
resistance to bile. The dam-negative mutant lacking DNA adenine methylase may
decrease envelop stability, leading to decrease resistance to bile. TolC is involved with
the AcrAB efflux pump system, and thus tolC mutant are more bile sensitive due to
the defective efflux pump.
Conclusions: Most of the bile-sensitive mutants are due to the disruptions of LPS
structures. It means that the structures of LPS play a major role in Salmonella
resistance to bile. Although some of the mechanisms of bile resistance are known,
much of the future work will be focused on how Salmonella ‘sense’ bile and the
resistance mechanisms this sense induces.
44
Panton-Valentine Leukocidin Genes Are Associated With Enhanced Skin
Manifestation and Inflammatory Response in Staphylococcal Scarlet Fever in
Children
Panton-Valentine Leukocidin 基因可以增強金黃色葡萄球菌性猩紅熱病童的皮膚
表現及發炎反應
Wen-Tsung Lo, Min-Hua Tseng, Ching-Shen Tang, Chih-Chien Wang
Department of Pediatrics, Tri-Service General Hospital, National Defense Medical
Center
羅文聰、曾敏華、鄧景升、王志堅
三軍總醫院小兒部, 國防醫學院
Background: Staphylococcal scarlet fever (SSF) is a rare disease and was first
described in 1900. The clinical features and outcomes in children with SSF caused by
Panton-Valentine leukocidin (PVL)-positive and PVL-negative Staphylococcus aureus
strains have not been compared prospectively.
Methods: The demographics, selected clinical features, laboratory values, and
outcomes of 50 consecutive children with community-acquired S. aureus SSF
prospectively identified during an 11-year period were collected for analysis.
Results: The male-to-female ratio was 1.94 and the median age was 37 months.
Cutaneous abscesses predominated among children with SSF. Methicillin-susceptible
and methicillin-resistant S. aureus (MSSA and MRSA, respectively) caused SSF in 27
and 23 children, respectively. Twenty-four isolates were PVL-positive (5 MSSA, 19
MRSA), 25 were PVL-negative (21 MSSA, 4 MRSA), and 1 MSSA was not available
for analysis. Polymerase chain reaction revealed that most (92%) contained only the
staphylococcal enterotoxin B (23 MSSA, 22 MRSA). By multivariate analysis,
children with PVL-positive isolates had significantly larger abscess size, higher white
blood cell count and C-reactive protein level, and longer duration of fever, generalized
scarlatiniform rash, and hospital stay. Most (89%) of 19 PVL-positive MRSA isolates
carried staphylococcal cassette chromosome mec VT and all were multilocus
sequence typing 59.
Conclusions: SSF caused by PVL-positive S. aureus strains were associated with
more enhanced skin manifestation and a greater systemic inflammatory response
compared with those caused by PVL-negative S. aureus. Clinical improvement with
incision and drainage was noted for most children with SSF caused by PVL-positive
MRSA strains, despite treatment with an ineffective antibiotic.
45
Comparison of Acute Lobar Nephronia and Uncomplicated Urinary Tract
Infection in Children
比較兒童的急性大葉性細菌性腎炎和非複雜性泌尿道感染
Ching-Chi Yang, Li-Ming Huang, Yong-Kwei Tsau, I-Jung Tsai, Ping-Ing Lee,
Chun-Yi Lu, Luan-Yin Chang
Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
楊清棋、黃立民、曹永魁、蔡宜蓉、李秉穎、呂俊毅、張鑾英
國立台灣大學醫學院附設醫院小兒部
Background: Ching-Chi Yang, Li-Ming Huang, Yong-Kwei Tsau, I-Jung Tsai,
Ping-Ing Lee, Chun-Yi Lu, Luan-Yin Chang Department of Pediatrics, National
Taiwan University Hospital, Taipei, Taiwan With more understanding about acute
lobar nephronia (ALN), ALN is much more frequently diagnosed in children with
urinary tract infection (UTI). This study was to assess the clinical manifestation,
micro-organisms and their antibiotic resistance in children hospitalized for ALN and
non-ALN community-acquired urinary tract infection.
Methods: We retrospectively reviewed the records of 265 previous healthy children
hospitalized due to the first-episode community-acquired febrile UTI between July
2004 and June 2007. By the results of renal ultrasonography (n=11) and computed
tomography (n=40), they were divided into ALN (n=51) and non-ALN (n=214)
groups. Their demographic and clinical characteristics, distribution of
micro-organisms, and their antimicrobial resistance were analyzed.
Results: ALN rate was 19.2% in previous healthy children hospitalized due to the
first-episode of community-acquired febrile UTI. Children with ALN were older
(1.86yr vs 0.81yr, P<0.05), and had longer fever duration before admission (4.7 days
vs 1.4 days, P<0.05), higher peak body temperature (39.5C vs 38.9C, P<0.05), higher
white cell count (18864/ul vs 15081/ul, P<0.05), higher C-reactive protein (9.0mg/dl
vs 3.5mg/dl, P<0.05) than non-ALN children. Fever persisted longer after antibiotic
usage in ALN children (2.7days vs 1.4 days, P<0.05) and they needed longer
hospitalization (8.6 days vs 6.7 days, P<0.05) and higher medical cost (38927 vs
30369 NT dollars, P<0.05). The rates of vesicoureteral reflux bwtween ALN and
non-ALN were not different (19% vs 16%). The major pathogen in ALN was E. coli
(90.2%) followed by Proteus spp (3.9%). E. coli in ALN children had higher
resistance rate to cotrimoxazole (65.9% vs 39.8%, P<0.05) and to ciprofloxacin
(27.3% vs 6.4%, P<0.05) than non-ALN children.
Conclusions: ALN are not uncommon in children with first-episode febrile UTI.
They had prolonged clinical course, higher inflammatory parameters, longer
hospitalization and higher medical cost. E. coli was the leading pathogen. Because of
the need of longer antibiotics, recognition of ALN in children is important.
46
麻疹群聚事件調查
陳如欣、洪敏南、陳婉青、李品慧、林慧真、王恩慈、巫坤彬、劉定萍
行政院衛生署疾病管制局
47
Evaluation of Renal Effects from Adulteration of Melamine-contaminated
Powdered Infant Formula in Taiwanese Infants and Toddlers
台灣雲林地區嬰幼兒因食用可能三聚氰胺污染的嬰幼兒配方奶粉對腎臟之影響
評估
Cheng-Hsien Tsai1, Chin-Shein Ku1, I-Jung Tsai2, Szu-Ta Chen2, Yong-Kwei Tsau2,
Yu-Feng Lin3, Jun Chen4, Kuen-Yuh Wu5
Department of Pediatrics, National Taiwan University Hospital Yunlin Branch1,
Department of Pediatrics, National Taiwan University Hospital 2, Department of
Nephrology, National Taiwan University Hospital Yunlin Branch and National Taiwan
University College of Medicine3, Department of Urology, National Taiwan University
Hospital Yunlin Branch4, Institutes of Occupational Medicine and Industrial Hygiene,
College of Public Health, National Taiwan University5
蔡政憲 1、顧清賢 1、蔡宜蓉 2、陳思達 2、曹永魁 2、林裕峰 3、陳淳 4、吳焜裕 5
台大醫院雲林分院小兒部 1,台大醫院小兒部 2,台大醫院雲林分院內科部 3,台大醫
院雲林分院泌尿部 4,台大公衛學院職業醫學與工業衛生暨環境醫學研究所 5
Background: 2008 年 9 月起中國大陸報導由於三聚氰胺污染奶粉和相關奶製品
造成 53,000 名嬰幼兒的腎臟不良影響。在雲林地區外籍配偶或大陸配偶家庭約
有 12,000，雲林地區嬰幼兒經常往來大陸福建、廣東與東南亞，本研究的目的是
利用病例對照組的研究，研究對象是家長主動帶來本院毒奶粉篩檢特別門診的兒
童，出生日期在 2005 年 1 月 1 日以後，或是過去三年曾經飲用已公布嬰幼兒配
方奶粉含有三聚氰胺者，必要條件為飲用配方奶粉需持續一個月以上，排除條件
包括早產，非順利生產，新生兒有先天性感染、或染色體數目異常之畸形、或母
親懷孕期間有成癮性藥物或酒精濫用。
Methods: 家長閱畢受試者同意書並署名後，(1)收集受試者的配方奶飲用繼往
史;(2) 收集 50cc 尿液檢體，儲存在-20 度冰箱，並以 LC/MS/MS Mass spectrometer
檢驗尿中 melamine 的濃度，該儀器的檢測靈敏度為 0.05 ppm(3)進行腎臟超音波
檢查。我們依據飲用的三聚氰胺的濃度分為三組，第一組(高暴露組)為飲用的配
方奶粉被公布三聚氰胺濃度大於 2.5 ppm 的嬰幼兒童；第二組（低暴露組）為配
方奶粉三聚氰胺濃度介於 0.05～2.5 ppm；第三組（控制組）為配方奶粉被公布
為未檢出三聚氰胺(小於 0.05 ppm)
Results: 從 2008 年 9 月 26 日至 10 月 27 日共完成 57 位嬰幼兒童尿液及腎臟超
音波的檢查，已飲用的配方奶粉中有 8 種被公布含有三聚氰胺，濃度介於
0.123~68.2 ppm，最早飲用年齡從新生兒到 36 月，飲用頻率從每月 900 公克到
5600 公克。第一組（高暴露組）共有七位小朋友，他們的三聚氰胺累積暴露量
平均為 819mg，平均年齡為 4.7 歲，全部都居住過大陸地區（100％）
，4 位(57%)
有潛血反應，3 位(43%)在超音波發現有腎臟小型鈣化點，1 位(14%)有高鈣尿，1
位(14%)尿中有三聚氰胺，濃度為 0.106ppm；第二組（低暴露組）共有 24 位小
朋友，其三聚氰胺累積暴露量平均為 9.9 mg，平均年齡為 2.6 歲，1 位(4.2%)居
住過大陸地區，6 位(25%)有潛血反應，2 位(8.3%)在超音波發現有腎臟小型鈣化
點，0 位有高鈣尿，9 位(37%)尿中有三聚氰胺，濃度為 0.065-0.156ppm；第三組
（控制組）共有 26 位小朋友，三聚氰胺累積暴露量推測為 0 mg，其平均年齡為
2.2 歲， 1 位(3.8%)居住過大陸地區，6 位(23%)有潛血反應，2 位(7.7%)有腎臟
小型鈣化點，0 位有高鈣尿，1 位(3.8%)尿中有三聚氰胺，濃度為 0.087 ppm。卡
方統計顯示，第一組有顯著較高的三聚氰胺的暴露量，和較高比率有高鈣尿和腎
臟鈣化點；第二組兒童尿液中有顯著較高的三聚氰胺偵測比率。
Conclusions: 曾經飲用三聚氰胺高暴露(>2.5ppm)的配方奶之兒童，有顯著較高
的三聚氰胺的暴露量，和較高比率有高鈣尿和腎臟鈣化點; 曾經飲用三聚氰胺低
暴露(0.05-2.5 ppm)的三歲以下兒童，和控制組兒童比較，在尿液及腎臟型態學上
並無統計上的差別。飲用低暴露配方奶的兒童尿液中有顯著較高的比率有三聚氰
胺，可能為正在飲用的反應，我們將繼續追蹤。
48
Pediatric Urolithiasis: Twenty Years Experience in a Medical Center
小兒泌尿道結石：單一醫學中心之二十年回顧
Jia-Horung Hung1, Hong-Lin Cheng2, Ya-Yun Huang3, Yuan-Yow Chiou3
Departments of Medicine, National Cheng Kung University, Tainan, Taiwan1
Department of Urology, National Cheng Kung University Hospital, Tainan, Taiwan2
Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan3
洪嘉鴻 1、鄭鴻琳 2、黃雅雲 3、邱元佑 3
國立成功大學醫學系 1 國立成功大學醫學院附設醫院泌尿科部 2 國立成功大學
醫學院附設醫院小兒部 3
Background: Urolithiasis is relatively uncommon disease in the pediatric population.
It occurs due to complicated interaction between several factors, including systemic
metabolic factors, structural urinary tract abnormalities, and infections. Yet the
clinical features and risk factors of pediatric urolithiasis in Taiwan are still
undetermined.
Methods: From 1988 to 2008, pediatric patients admitted to NCKU hospital for
urolithiasis are assessed retrospectively. Clinical features and risk factors are
evaluated according to the age of onset or the locations of the stones.
Results: Totally 35 patients are included, with 18 males and 17 females. The mean
age at diagnosis of urolithiasis was 11.6 years old (16 months old–18 y/o). Before 6
years old, male: female ratio is 3:1. 83% of patients had stones in the upper urinary
tracts (kidney and ureter), while 17% of patients had stones confining to the lower
urinary tract (bladder and urethra). The initial symptoms of upper tract stones
included flank pain (52%) and gross hematuria (31%), while lower tract stones had
diverse initial presentations. Lower tract stones had strong correlations with structural
abnormalities. As to risk factors, 40% of patients had hypercalciuria, 29% had
anatomical abnormalities. Urinary tract infection was detected in 43% of patients, and
the prevalent pathogen was Proteus mirabilis. 20% of patients had more than one risk
factor. Before 5 years old, infection plays a more important role. For upper tract
stones, 31% received medical treatment, 34% received extracorporeal shock wave
lithotripsy, 17% received ureterorenoscopic stone manipulation, and 13% received
open lithotomy. For lower tract stones, 83% received electrohydraulic lithotripsy, 17%
received cystolithotomy.
Conclusions: Male predominates in having urolithiasis before 6 years old. Initial
symptoms include flank pain and gross hematuria. It is not uncommon to see more
than one risk factor in one patient. Well-designed study is needed for the elucidation
of the stone formation.
49
Acute Lobar Nephronia is not the Midpoint in the Spectrum of Upper Urinary
Tract Infections between Acute Pyelonephritis and Renal Abscess
急性大葉性腎炎並非上泌尿道感染之中點
Chi-Hui Cheng, Yong-Kwei Tsau1, Tzou-Yien Lin
Department of Pediatrics, Chang Gung Children’s Hospital, Chang Gung Memorial
Hospital, Taoyuan, Taiwan National Taiwan University Hospital, Taipei, Taiwan1
鄭積慧、曹永魁 1、林奏延
長庚兒童醫學中心兒童內科部 國立台灣大學醫學院附設醫院小兒部 1
Background: To examine the place of acute lobar nephronia (ALN) in the spectrum
of upper urinary tract infections between acute pyelonephritis (APN) and renal
abscess.
Methods: The medical records of 115 patients diagnosed with APN, ALN, or renal
abscess using computed tomography (CT) were reviewed retrospectively in terms of
demographic characteristics, clinical presentation, and laboratory findings. The CT
lesions and patterns of the ALN were checked on contrast-enhanced CT films, and the
volume of the CT lesions (the extent of renal involvement) was estimated in every
patient. Then, the correlation between the clinical presentation and CT lesions was
examined.
Results: The study included 21 patients with APN, 85 with ALN (63 simple ALN, 22
complicated ALN), and 9 with renal abscesses. The volume fraction of the CT lesions
correlated well with the duration of fever before (P < 0.001) and after (P < 0.001)
treatment in patients with APN or simple ALN, while only the correlation between
fever duration after treatment and the volume fraction of CT lesions (P < 0.001) was
significant in patients with complicated ALN or renal abscess. No treatment failures
were found with arbitrarily different treatment periods for all patients.
Conclusions: We suggest that simple ALN be regarded clinically as the progression
of APN and recommend antibiotic treatment for 2 weeks. By contrast, complicated
ALN is a distinct, more severe disease entity requiring a 3-week regimen, and it may
relate to or progress to renal abscess. ALN is not the midpoint in the traditional
dynamic spectrum of upper urinary tract infections between APN and renal abscess.
50
Comparison of Virulence Variations on MDCK Monolayers by Escherichia coli
Isolated from Acute Lobar Nephronia and Acute Pyelonephritis
以 MDCK 為模式: 比較來自於急性腎盂腎炎和急性大葉性腎炎細菌之毒性
Chi-Hui Cheng, Chen-Yen Kuo, Lin-Hui Su1, Tzou-Yien Lin
Comparison of Virulence Variations on MDCK Monolayers by Escherichia coli
Isolated from Acute Lobar Nephronia and Acute Pyelonephritis
鄭積慧、郭貞孍、蘇玲慧 1、林奏延
長庚兒童醫學中心兒童內科部 長庚醫院臨床病理科 1
Background: Escherichia coli is the most common pathogen associated with acute
lobar nephronia (ALN), a clinically more severe parenchymal inflammatory disease
that may require a longer duration of antibiotic treatment than that for acute
pyelonephritis (APN). This study was conducted to unravel the virulence differences
between clinical isolates of E. coli recovered from pediatric ALN and APN patients.
Methods: A total of 88 urinary isolates of E. coli were investigated. They were
identified previously from radiologically diagnosed ALN and APN patients and had
been molecular characterized for the presence of some important urovirulence genes.
Madin-Darby canine kidney (MDCK) epithelial cells were used as an in vitro model
to further investigate the virulence characteristics, including adhesion, penetration and
cytotoxicity, of these E. coli isolates. Statistic analysis was performed using SAS
systems for Window (version 8.01).
Results: Multivariate logistic regression analysis indicated that ALN isolates were
more likely to show adhesion (p<0.05; odds ratio [OR], 3.10; 95% confidence interval
[CI], 1.12-8.59) and cytotoxicity (p<0.001; OR, 9.93; 95% CI, 2.93-33.69). However,
no difference in the penetration ability was noted between the ALN and APN isolates.
Moreover, the cytotoxicity was significantly associated with the presence of a papG
III gene (p<0.05; OR, 5.25; 95% CI, 1.25-22.06), while the adhesion was negatively
associated with a cnf1 gene (p<0.005; OR, 0.08; 95% CI, 0.02-0.45).
Conclusions: The ability to adhere to and produce cytotoxicity against uroepithelial
cells appears a prerequisite factor for E. coli to cause severe bacterial kidney infection,
such as ALN, in pediatric patients.
51
Melatonin Attneuates Renal Injury Induced by Bile Duct Ligation
褪黑激素保護膽道阻塞引起的腎臟傷害
You-Lin Tain1, Chih-Sung Hsieh2, Chih-Cheng Chen1, Li-Tung Huang1
Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung, Chang Gung
University, Taiwan1 Department of Pediatric Surgery, Pingtung Christian Hospital,
Pingtung, Taiwan2
田祐霖 1、謝志松 2、陳志誠 1、黃立同 1
高雄長庚醫院兒童內科部 1 屏東基督教醫院兒童外科 2
Background: Identifying and treating kidney injury in cirrhosis is important since the
incidence of acute kidney injury (AKI) is high and renal dysfunction is a powerful
predictor of outcome. We recently found cholestasis in the young rats caused by bile
duct ligation (BDL) increase oxidative stress, which is prevented by melatonin. We
hypothesize that asymmetric and symmetric dimethylarginine (SDMA & ADMA) is
involved in BDL-induced oxidative stress and kidney injury. We also intend to
elucidate whether increased ADMA is due to increased protein arginine
methyltransferase (PRMT1, ADMA-synthesizing enzyme) and decreased
dimethylarginine dimethylaminohydrolase (DDAH, ADMA-metabolizing enzyme).
Methods: Three groups of rats (17 D) were sacrificed 14 days after the surgery: sham
(N=7), untreated BDL rats (N=6), and melatonin-treated BDL rats (N=6, BDL+M).
Melatonin-treated BDL rats received daily melatonin 1 mg/kg/day i.p. injection.
Results: BDL rats had higher plasma AST, ALT, direct and total bilirubin, and
ammonia levels than shams. Elevated AST and ammonia levels were partially
prevented by melatonin therapy. There is no difference of Cr and % of
glomerulosclerosis among three groups. Plasma ADMA and SDMA levels were
higher in BDL rats vs. shams, which were prevented by melatonin therapy. In liver,
PRMT1 was higher in both BDL groups vs. shams. We found no difference of
DDAH1 expression in liver among three groups; whereas DDAH2 expression was
higher in BDL+M vs. BDL group. In kidney, we found no difference in PRMT1,
DDAH1, and DDAH2 abundance among three groups. DDAH activity was increased
in BDL+M group in both liver and kidney. Oxidative stress (represented by p22phox
and GSH/GSSG) is induced by BDL whereas prevented by melatonin therapy.
Conclusions: Young BDL rats develop AKI (represented by elevated SDMA),
increased ADMA, and increased oxidative stress. Melatonin therapy can prevent
kidney injury via reduction of ADMA (by increasing DDAH activity) and oxidative
stress (by increasing GSH/GSSG).
52
B Cell Depletion Therapy on Pediatric Systemic Lupus Erythematosus
抗 B 細胞療法於兒童紅斑性狼瘡的治療
Ya-Yun Huang, Ching-Song Lee, Yuan-Yow Chiou
Departments of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan
黃雅雲、李青松、邱元佑
國立成功大學醫學院附設醫院小兒部
Background: Systemic lupus erythematosus (SLE) is often more severe in children
than in adults, and therefore requires aggressive treatment. However, adverse effects
of current medications often limit the therapeutic efficacy. Rituximab has been
demonstrated to be effective in some pediatric autoimmune diseases. We report our
experience in management of SLE cases with rituximab.
Methods: Four SLE girls (mean age, 13.7 years) who received rituximab therapy
were reviewed in our hospital. Indications of rituximab therapy were those who
suffered from severe adverse effects or those who were refractory to standard
immunosuppressive treatment. Four doses of rituximab (375mg/m2) were given
intravenously at an interval of two weeks, combined with low doses of corticosteroids
and mycophenolate mofetil. Clinical, hematological, biochemical and immunological
parameters were followed and compared before and after treatment.
Results: Of the four girls, three were diagnosed with lupus nephritis; two showed as
WHO class IV (A) and one as WHO class II (B). The other one girl experienced
recurrent skin symptoms of SLE frequently and short stature of steroid side effects.
After complete treatment of Rituximab, hemolytic anemia and impairment of renal
function were improved in 2 of 3 who showed with nephritis. Symptom free was
achieved in patient with recurrent malar rash. During these follow-up (3 ± 1.7 months),
free of symptoms were still kept. Anti-nuclear antibody level also decreased in this
three patients. Depletion of peripheral blood B cells was effective and it could last
through the follow-up. Besides, it corresponded with the clinical response and no
apparent side effects could be observed in this follow-up.
Conclusions: In our preliminary data, children could tolerate well with Rituximab
therapy and it also could be a rescued clinical effectively combined therapy.
53
Set up in Vitro Polycystin 1 Knock Down Cell Line to Investigate Tubulogenesis
and Cyst Formation – A Preliminary Study
建立低表現多囊腎蛋白表現之細胞株以研究腎小管及囊狀結構之形成-先期研究
Yuan-Yow, Chiou1, Si-Tse, Jiang2
Department of Pediatrics, National Cheng-Kung Medical Colledge and Hospital,
Tainan 1 Institute of Molecualr Biology, Academia Sinica, Taipei 2
邱元佑 1、蔣思澈 2
成大醫院小兒科 1 中央研究院分子生物研究所 2
Background: Polycystic kidney (PKD) is a genetic disorder characterized by the
growth of numerous cysts in the kidneys. Autosomal PKD is one of the most
-common life-threatening inherited cystic kidney diseases (90%) characterized by the
development of gradually enlarging renal cysts and a progressive loss of normal
kidney tissue that can lead to chronic renal failure. In previous study, we produce low
levels of full-length Pkd1-encoded protein mouse model suggesting that low
polycystin1 (PC1) expression is sufficient for renal cyst formation in ADPKD. For
further studies, we utilize siRNA technology to knock down the polycystin 1 protein
expression in immortalized renal tubular cell line to investigate the fundamental study.
Methods: Here, stable knockdown of PC1 in M-1 mouse CCD cells was achieved by
lipo-polymeric formulation, developed and optimized for transfection of a specific
small interfering RNA for Pkd1. After transfection, stable clone of siRNA PKD1 cell
lines were sorted by FACS and selected by blasticidin. For immunodetection, cells
were lysed in lysis buffer and supplemented with a cocktail of protease inhibitors.
PC1 was detected using the affinity-purified rabbit anti-PC1 polyclonal antibody
which was generated by Dr. Jiang. Meanwhile, proliferation assay was performed and
plate 5×103 M1 or stable clone cells in 200ul media per well in a 96 well plate.
Incubated for 1-5 days to allow the cells to attach and grow in the wells. MTT
solution was added to each well with shaded and incubated. Finally, results were read
by ELISA at OD 560nm and 670, respectively. Besides, for tubulogenesis and cysts
formation, M1 cells and stably transduced cells were trypsinized to a single-cell
suspension and resuspended at a concentration of 1×105 cells/ml in an ice-cold
collagen solution. The cell suspension then was dispensed at 2.5ml/well in six-well
plated and allowed to gel for 20 min at 37℃ before being overlaid with 2.5ml of
fibroblast-conditioned medium. The conditioned medium was changed daily, and
pictures were taken at day 7.
Results: PC1 knockdown created a condition of haploinsufficiency that led to
hyperproliferation, increased adhesion to collagen type I. It was shown, in vitro study,
that the suppression of PC1 was evidenced with the increased expression of
laminin-γ3. Decreased tubulogenesis and increased cystic formation were also shown
when they grown in gel culture system.
Conclusions: According to our result, stable down-regulation of PC1 cell lines could
be created by small interfering RNA technique. Hyper-proliferation and cystic
formation also are shown as in human ADPKD disease or in vivo Pkd1 knockdown
transgenic mouse. Meanwhile, over-expression of laminin-γ3 is evidenced in these
siRNA PKD1 cell lines model, too. Then, we can suggest that these cell lines are
adequate for further investigation of the pathogenesis of human ADPKD disease.
54
Hepatitis B Vaccination in Very Low Birth Weight Infants: Long-term Follow-up
of Immunogenicity
極低體重早產兒接種 B 型肝炎疫苗之長期追蹤
Chien-Yi Chen, Huey-Ling Chen, Hung-Chieh Chou, Po-Nien Tsao, Wu-Shiun Hsieh,
Mei-Hwei Chang
Department of Pediatrics, Hospital and College of Medicine, National Taiwan
University, Taipei, Taiwan
陳倩儀、陳慧玲、周弘傑、曹伯年、謝武勳、張美惠
國立台灣大學醫學院附設醫院小兒部
Background: The current hepatitis B virus (HBV) vaccination schedule of preterm
infants in Taiwan is three doses in 6months but delayed the first dose until attained
weight of 2,000-2,200gm. However, the long-term efficacy of the delayed program in
endemic area has never been reported.
Methods: In the present study, 602 surviving VLBW preterm infants who were
admitted to the National Taiwan University Hospital during 1995-2006 were invited
and 156 of them were recruited. Serum HBsAg and its antibody (anti-HBs) were
tested by enzyme immunoassay after informed consents. Anti-HBs is considered
positive if the titer is above 10 mIU/mL.
Results: All of the enrolled patients are HBsAg negative. The anti-HBs seropositive
rate is 82.9%, 73.1%, 33.3% and 20.8% at 2-3, 4-7, 8-11, 12-13 years of age,
respectively. Half of these patients received the first vaccination at the age of more
than 60 days, and 29 patients (18.6%) at the age of more than 90 days. Seven of 24
patients who were born with HBsAg-positive mother did not received hepatitis B
immunoglobulin, but none of them became infected by HBV.
Conclusions: The delayed program of hepatitis B vaccination in VLBW preterm
infants provides long-term protection up to at least 13 years.
55
Neurodevelopmental Outcome of Posthemorrhagic Hydrocephalus in Children
兒童出血後水腦之神經發展預後因子
Fong-Fong Lim3, Jui-Ming Hu1, Yan-Yan Ng1, Pao-Hui Chiu2, Pen-Hua Su1, Jia-Yuh
Chen1, Inn-Chi Li2
Department of Neonatology1, Chung-Shan Medical University; Department of
Pediatric Neurology2 Chung-Shan Medical University; Department of Pediatrics3,
Chung-Shan Medical University, Taichung, Taiwan; 2 3 4 5
林芳芳 3、胡瑞銘 1、黃元韻 1、邱寶慧 2、蘇本華 1、陳家玉 1、李英齊 2
中山醫學大學附設醫院新生兒科 1; 中山醫學大學附設醫院小兒神經科 2; 中山醫
學大學附設醫院 小兒科 3
Background: Posthemorrhagic hydrocephalus (PHH) is a major complication after
intraventricular hemorrhage (IVH), which will cause a neurodevelopmental
consequence. The prognosis factors to neurodevelopmental outcomes of childhood
posthemorrhagic hydrocephalus are noteworthy.
Methods: We retrospectively reviewed the cases of neonatal IVH in an interval of
7-year, grading 2 to 4, with the consequence of PHH. Cases had congenital or
chromosomal abnormality, meningitis, or extensive cystic encephalomalacia were
excluded. Total 30 PHH were enrolled. To analyze neurodevelopmental outcomes
including the mentality and performance results in Bayley Scales of Infant
Development II, which examined at corrected age of over 1-year-old. The prognostic
factors were presumed to include gestational age, birth body weight, Apgar score,
severity of respiratory distress syndrome, focal cystic periventricular leucomalacia
(PVL), laboratory data of cerebral spinal fluid including lowest glucose, highest total
protein and maximal red blood cell counts, ventriculoperitoneal shunt dependency,
and degree of progressive hydrocepcephalus- rapidly or slowly progressive. The
statistic significance is determined by one-way ANOVA and linear regression analysis
by SPSS 14th edition.
Results: Thirty children included 14 deaths and 16 survivors. Of those prognostic
factors, shunt dependency (p=0.03) and degree of progressive hydrocephalus
(p=0.036) were significant to mentality. Other factors including IVH grading
(p=0.144), focal cystic periventricular leucomalacia (p=0.183) and Apgar score were
not significant. The performance results are determined predominantly by shunt
dependency (p=0.002). Others like degree of progressive hydrocephalus (p=0.055),
focal cystic PVL (p=0.056), gestational age (p=0.519), birth body weight (p=0.383),
gender, Apgar score, and laboratory data of cerebral spinal fluid were not significant.
To surviving, gestational age (p=0.038), degree of progressive hydrocephalus
(p=0.033), and IVH grading (p=0.009) were significant.
Conclusions: Shunt dependency is a critical prognostic factors being inverse
correlation with neurodevelopmental outcomes at corrected age over 1-year old in
childhood PHH. Factors relevant to mentality and to performance are not obviously
different.
56
Current Prevalence and Pathogen Distribution of Neonatal Sepsis Among VLBW
Preterm Infants: Comparison of 10 Year Interval
目前極低體重早產兒敗血症之發生率及其致病菌種分佈研究
Wai-Ho Lim, Reyin Lien, Chi-Ming Chu, Jen-Hei Fu, Yu-Chern Huang*
Division of Neonatology, and *Infectious disease, Department of Pediatrics, Chang
Gung Children’s Hospital, Chang Gung University College of Medicine, Taoyuan,
Taiwan
林偉豪、林瑞瑩、朱世明、傅仁煇、黃玉成*
林口長庚醫院兒童醫學中心新生兒科、感染科
Background: Neonatal sepsis contributes to great mortality and morbidity among
VLBW infants. Prevalence and patterns of pathogen distribution of sepsis in NICU
vary with time and this information serves as a guild for selection of empirical
antibiotics. This study is to determine current incidence, pathogen distribution and
clinical characteristics of neonatal sepsis in VLBW preterm infants.
Methods: Medical records of VLBW infants admitted to NICU of CGMH during the
18 months period from July 2007 to Dec. 2008 were reviewed. The numbers of
positive blood culture, age of sepsis onset, pathogen distribution and mortality rate
were described and compared to that of the same unit 10 years ago.
Results: 326 VLBW infants were admitted to NICU of CGMH with 40 (12.3%)
patients developed at least one episode of blood culture proven sepsis. There were 23
(57.5%) G(+) organisms with CONS 20(50%) , Staphylococcus aureus (ORSA) (5%)
and 1 other (2.5%). There were 17 episodes of G(-) sepsis (42.5%) with Acineto.
Baumannii 5 (12.5%), Klebsiella pneumoniae 5 (12.5%), Klebsiella oxytoca 1 (2.5%),
E. Coli 5, including 1 ESBL strain (12.5%), and Enterobacter cloacae 1 (2.5%). No
fungal sepsis was recovered. The distribution one decade ago (1997) was G (+) 69.2%:
CONS (41.6%), S. aureus (20.5%, including ORSA 17.8%), Non-GBS (4.9%), G (-)
27%: Enterobacter (10.8%), Klebsiella (6.5%), E.coli (6.5%), and fungi 3.8%, all of
Candida species. Current median age of disease onset and mortality rate were 24 days
and 4.3% for G (+) sepsis; 16 days and 11.8% for G (-) sepsis respectively
Conclusions: Broad spectrum antibiotics covering both Gram positive and Gram
negative pathogens should be considered as empirical regimens whenever sepsis is
suspected. There’s a shift of distribution in the pathogen over the last decade, and the
emergence of ESBL organisms warrant meticulous infection control interventions.
57
Invasive Fungal Infection in Very Low Birth Weight Infants: High Survival Rate
under Prompt Management
極低出生體重早產兒之侵入性黴菌感染：及時治療與高存活率
Cheng-Yi Wang, Jui-Hsing Chang, Hsin-An Kao, Chyong-Hsin Hsu, Han-Yang Hung,
Chun-Chih Peng, Wai-Tim Jim
Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan
王臻誼、張瑞幸、高信安、許瓊心、洪漢陽、彭純芝、詹偉添
馬偕紀念醫院小兒部
Background: To study the clinical experience of invasive fungal infection in very low
birth weight (birth weight < 1500 gram) infants.
Methods: We reviewed the medical records of patients admitted to the NICU of
Mackey Memorial Hospital from January 2004 through December 2008, who were
diagnosed as invasive fugal infection. The perinatal history, clinical presentation, and
treatment course were analyzed.
Results: 26 patients were enrolled. 21 of 26 patients (80%) were ELBW infants (birth
weight < 1000 gram). Candida was isolated from blood in 14 patients, from urine in 7
patients, and from ascites in 1 patient. Four patients were diagnosed as invasive fungal
dermatitis. The median gestational age was 25.9 weeks, the median birth weight was
802g, and the median age at the onset of illness was 11.5 days. Seventy-seven percent
of the patients received third-generation cephalosporin prior to onset of illness. All
except one patient had central line insertion with parenteral nutrition before onset of
illness. The most common pathogen was Candida albicans (73%), followed by
Candida Parapsilosis(19%). The clinical manifestations include respiratory
decompensation(42%), thrombocytopenia(38%), leukocytosis (34%), macerated skin
lesions (34%), hyperglycemia(23%), and pneumonia(19%). All except one patient
received a complete course of antifungal treatment at least 2 to 3 weeks with
amphotericin B therapy. Central venous catheter was removed once fungus was
isolated from blood. Only two patients died. The survival rate was 92%.
Conclusions: Invasive fungal infection mainly occurred in ELBW infants. High index
of suspicion and appropriate evaluation are mandatory. Timely management including
amphotericin B therapy, removal of central venous catheter and appropriate
supportive care were associated with good short-term outcome.
58
Neonatal Sepsis : a 6-year Analysis in a Neonatal Care Unit in Taiwan
新生兒敗血症
JUN-HO WU, HUNG-CHIEH CHOU1, WU-SHIUN HSIEH1, PO-NIEN TSAO1,
CHIEN-YI CHEN1
Department of Pediatrics, Branch for Women and Children, Taipei City Hospital,
Taipei, Taiwan Departments of Pediatrics, National Taiwan University Hospital and
National Taiwan University College of Medicine, Taipei, Taiwan (1)
吳俊厚、周弘傑 1、謝武勳 1、曹伯年 1、陳倩儀 1
台北市立聯合醫院婦幼院區小兒科 臺大醫院小兒部(1)
Background: Neonatal sepsis is the main problem in neonatal intensive care resulted
in significant morbidity and mortality. The purpose of this study was to evaluate the
causative pathogen, drug sensitivity, hemogram, clinical courses and mortality rate of
neonatal sepsis in a Taiwan medical center.
Methods: Neonates admitted to NICU at NTUH from January 2001 through
December 2006 were included. Patients were divided into early onset group and late
onset group if culture positive within 7 days of life or later, respectively.
Results: A total of 109 episodes of sepsis were identified in 100 neonates. The
incidence of sepsis was 4.06% among all NICU admissions. The most neonates in
early onset group were term infants while Very Low Birth Weight (VLBW) and
preterm infants accounted majority in late onset group. In early onset group, the
leading pathogens were group B streptococcus (GBS) (36%) and Escherichia coli (E.
Coli) (26%). GBS had more meningitis involvement but lower mortality compared
from E. Coli. The most common causative microorganism in late onset sepsis were
Coagulase-negative staphylococcus (CONS) (40%) and Candida (15%). The sepsis
related mortality rates were higher in early onset group (10%) than late onset group
(7%).
Conclusions: GBS was the leading pathogen in early onset group with high
meningitis involvement. GBS screening and IAP guideline should be popularized in
our country to prevent early neonatal sepsis. Candida parapsilosis was the
predominant fungal infection pathogen in our NICU. Restrictive hand-washing
procedures and diminish central line insertion might prevent late onset sepsis.
59
Five year neurological outcome in patients with neonatal seizures
新生兒抽搐之五年的神經學預後
Tzu-Hui Lei1, Reyin Lien1, Kuang-Lin Lin2, Jen-Fu Hsu1, Pong-Hong Yang1,
Chang-Yo Yang1
Division of Neonatology, Department of Pediatrics, Chang Gung Children’s Hospital,
Chang Gung University College of Medicine, Taoyuan, Taiwan 1Division of Pediatric
Neurology, Chang Gung Memorial Hospital, Taoyuan2
雷慈暉 1、林瑞瑩 1、林光麟 2、徐任甫 1、楊鵬弘 1、楊長佑 1
林口長庚醫院兒童醫學中心、新生兒科 1 林口長庚醫院兒童醫學中心、兒童神經
科2
Background: Neonatal seizures are markers for prenatal and neonatal brain disorders,
and predict later neurological sequelae during childhood and adulthood. Seizures can
be isolated clinical signs or one expression of a neonatal encephalopathic state.
Regardless of the etiology, neonatal seizures represent important role for assessing
risk for later sequelae in children, ranging from epilepsy to developmental disorders.
Objectives: This study was aimed to examine the neurological outcome in patients
with neonatal seizures, and to correlate their outcome with different etiologies of the
seizure.
Methods: We retrospectively enrolled those infants who experienced seizures during
0 to 60 days of age and was admitted to the NICU of Chang Gung Children’s Hospital
from Jan. through Dec. 2003. Patients’ gestational age at birth, age of seizure onset,
seizure etiology, image of the brain, EEG findings, and neurological outcome at 6, 12,
24 and 60 months of age were collected. These clinical outcomes are described and
compared among infants with different etiologies.
Results: There were 56 infants with EEG confirmed neonatal seizure enrolled,
including 31 male and 25 female. Of these, 4 patients expired (2 holoprocencephaly,
and 2 inborn errors of metabolism: urea cycle disorder, and MMA), and 10 patients
lost follow up before 1 year of age. Of the remaining 42 infants included in our study,
there were 16 preterm and 26 full-term. As for distribution of seizure etiologies, there
were hypoxic-ischemic encephalopathy due to perinatal asphyxia (8), hypocalcemia
(6), intracranial hemorrhage (IVH and SDH, 3), meningitis (3), and unidentified (22).
When followed up to 5-year-of-age, 14% (6/42) had mental retardation and global
developmental delay, 10% (3/42) had cerebral palsy, 7% (3/42) had epilepsy and 69%
(29/42) had no neurodevelopmental sequela. Seizures due to HIE was a much higher
risk for neurological sequela than due to hypocalcemia (6/8 vs 0/6). Comparing
outcomes caused by unidentified etiology and by HIE, the later had higher risk for CP
(0/11 vs 2/7, p=.05) but no difference in mental retardation/global delay (3/11 vs 5/7,
p=.07). There were 14/42 (33%) patients with abnormal image findings, of which all
with encephalomalasia/leukomalacia (4/4) developed CP. There were 7 patients with
EEG showing cortical dysfunction, and 3 had CP, 2 had global delay, and the other 2
were normal. For initial seizure control, 33/42 received phenobarbital alone, 4/42
needed to combine with phenytoin and 5 received no anticonvulsants. Of the 37
patients who received anticonvulsants initially, 7 required long-term treatment, and
the median duration of anticonvulsant treatment was 4 months.
Conclusions: Neonatal seizures, especially if result from HIE, pose high risk for later
neurological derangement. However, seizures due to hypocalcemia have excellent
prognosis.
60
Neonatal Listeriosis in Taiwan, 1990-2008
台灣新生兒李斯特菌感染,1990-2008
Li-Yi Tsai, Chyong-Hsin Hsu1, Peng-Hong Yang2, Hong-Chih Lin3, Chien-Yi Chen,
Hung-Chieh Chou, Po-Nien Tsao, Wu-Shiun Hsieh
Department of Pediatrics, National Taiwan University Hospital;Department of
Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan1; Department of Pediatrics,
Chang Gung Hospital,Taoyuan,Taiwan2, Department of Pediatrics, China Medical
University Hospital, Taichung, Taiwan3 ;
蔡立儀、許瓊心 1、楊鵬弘 2、林鴻志 3、陳倩儀、周弘傑、曹伯年、謝武勳
國立台灣大學醫學院附設醫院小兒部、馬偕醫院小兒部 1、 林口長庚醫院兒童內
科部 2 、中國醫藥大學附設醫院兒科部 3
Background: Listeria monocytogenes is an important pathogen in neonatal infections
in Western countries with 20-30% fatality rate. There is limited information of
nationwide neonatal listeriosis investigation in Eastern countries. The purpose of this
study was to delineate the occurrence and clinical picture of neonatal listeriosis in
Taiwan.
Methods: A literature review of neonatal listeriosis as reported in Taiwan and a
questionnaire based survey from medical centers in Taiwan from 1990 to 2008 were
made.
Results: A total of 17 cases including 16 neonatal patients (11 male, 5 female ) and 1
case of intrauterine fetal demise were identified. 14 cases were found from the survey
of four medical centers and another three collected from the literature review. 14 were
identified after 2000 and 3 prior to 2000. The age of onset was less than 3 days in all
cases. Most of the patients were preterm infants (14/16, 87.5%) and central nervous
system infection was common (7/16, 43.8%). The mean gestational age was 32.4
weeks (range 26-38 weeks). Most of their mothers had a history of fever or flu-like
symptoms before delivery. Chorioamnionitis was noted in five mothers, and two
mothers had L. monocytogenes bacteremia. Abnormal cerebrospinal fluid with
pleocytosis and hypoglycorrhachia, and complicated hydrocephalus were not unusual
among patients with central nervous system involvement. L. mononcytogenes was
identified from blood in 14, cerebrospinal fluid in 4, gastric aspirate in 2, maternal
blood in 2 and maternal endometrial culture in 1. The overall mortality rate was up to
25%.
Conclusions: Despite of limited information, our findings suggest that listeriosis may
emerge as an important health threat among newborn infants during recent decade in
Taiwan.
61
Hyponatremia In Young Infants：A 6-Year Analysis of A Medical Center
嬰兒低血鈉症:一醫學中心六年之分析
Ming- Hsia Lin, Hsiang- Yu Lin, Hsin-Yang Hsieh, Hsiao-Yu Chiu, Hung-Chih Lin,
Bai-Horng Su
Department of Pediatrics, China Medical University Hospital, Taichung, Taiwan.
林明霞、林湘瑜、謝欣洋、邱曉郁、林鴻志、蘇百弘
中國醫藥大學附設醫院兒科部
Background: To analyze the epidemiology and predisposing factor of hyponatremia
(plasma sodium ≦130 mmol/L) in young infants in CMUH.
Methods: A retrospective study was performed between October 2002 and November
2008. 5503 infants who were admitted to NICU or SBR of our hospital were enrolled
and one hundred and thirty four infants with plasma sodium ≦130 mmol/L were
included for analysis. Late- onset hyponatremia was defined beyond the first week of
life. Chart data was collected on gestational age, birth weight, plasma sodium and
clinical presentation.
Results: The incidence of hyponatremia in young infants in our hospital is 2.43%
(134/5503). The median gestational age was 28 weeks (23-41week) and the median
birthweight was 1010gm (range 545 –4120gm). Among 134 patient, 41 (30.6%)
infants developed hyponatremia in the first week of life, 15(11.19%) in the second
week of life, 19 (14.18%) in the third week of life, 14 (10.45%) in the forth week of
life, 20 (14.93%) in the fifth week of life, and remainder 25 (18.65%) developed
hyponatremia beyond the fifth week. 26 (19.40%) of 134 infants was proved sepsis by
positive culture and 18 (13.4%) of 134 infants was considered to be related with
operation because of the temple sequence. The percentage of late- onset hyponatremia
was 69.4% (93/134) and mostly (76.34%, 71/93) developed in premature baby.
Conclusions: Sepsis is usually the first consideration of diagnosis in infants with
hyponatrmia due to the septic-like clinical manifestations. The late-onset
hyponatremia mostly developed in the premature infants and is idiopathic. A
prospective study such as adrenal insufficiency induced hyponatremia is warranted.
62
Correlation between the Development of Bronchopulmonary Dysplasia and
Early Postnatal Oxygen Status: A Case-Controlled Study
肺支氣管發育不良的形成與出生後早期血氧濃度的關係研究
Chang-Yo Yang, Reyin Lien, Peng-Hong Yang, Ming-Chou Chiang, Tzu-Hui Lei,
Wai-ho Lim
Division of Neonatology, Depts. of Pediatrics, Chang Gung Children’s Hospital,
Chang Gung University College of Medicine, Taoyuan, Taiwan
楊長佑、林瑞瑩、楊鵬弘、江明洲、雷慈暉、林偉豪
林口長庚兒童醫學中心兒童內科部新生兒科；長庚大學醫學院
Background: Background: Preterm infants are prone to damage caused by oxygen
free radicals. Significant morbidities of prematurity such as bronchopulmonary
dysplasia (BPD) can be caused by inappropriate oxygenation as early as during
immediate postnatal life. There’s no consensus as to what the optimum oxygenation
should be for these infants. Objectives: We aimed to examine if there’s any difference
in 1) levels of oxygenation or 2) degree of oxygenation variability, during the first 72
hours of life between VLBW infants who developed BPD and ROP and those who did
not.
Methods: Patients and Methods: This is a retrospective case-controlled study
enrolling VLBW infants who were inborn and cared for in the NICU of Chang Gung
Children’s Hospital between Jan. 2005 and 2007. We identified those preterm infants
with BW less than 1500 gm who developed moderate to severe BPD (Gr. A, n= 40),
and for each BPD case we matched with one infant with comparable GA, BW and
Apgar scores but did not have BPD (Gr. B, n=40). Hourly oxygen saturation (SpO2)
for the first 72 hours of life was retrieved from their medical records. Mean value and
standard deviation of SpO2 was compared between the two groups. Also compared
was the variability of oxygen saturation reflected as the highest oxygen saturation
(HO2) level, the lowest oxygen saturation (LO2) level, the differences between the
two (ΔO2), and the standard deviation of SpO2 in both groups.
Results: Results: There were 252 inborn VLBW infants during the period, of whom
213 survived until 36 weeks PMA and met the diagnostic criteria for BPD screening.
BPD of moderate to severe degree was diagnosed in 71 (33.3%) of them. We were
able to match 40 infants in the study and control groups each, with mean GA of
29.0±2.7 and 30.0±2.6 wks, mean BW of 1125±250 and 1130±250 gms, and mean
Apgar scores of 6±1 and 7±1 in Grs. A and B, respectively. Mean±SD (range) oxygen
saturation on DOL 1, 2 and 3 were 94±2% (92-96 %), 94±1% (90-97 %) and 94±2%
(92-97 %) for Gr. A, and 95±1% (93 -97 %), 95±2 % (93 -98 %) and 95±2% (92-98 %)
for Gr. B. There was no statistically significant difference between the two groups.
However, patients in Gr. A had a higher FiO2 on DOL 3: (32.2±8.1% vs. 23.8±3.6%;
P=.03). The HO2 value (mean±SD) for Gr A and B were 99.3±0.3% and 99.8±0.4%,
and LO2 were 68.0±22.1% and 85.0±5.6%, respectively. The ΔO2 were 31.8±21.8%
vs. 14.8±5.7%. Value of standard deviation in SpO2 at first 72 hours of life for Gr A
and B were 3.79±0.78 and 2.73±0.60 (P=.021), respectively.
Conclusions: Conclusion: Our study revealed a higher oxygen requirement and a
greater degree of variability in oxygen saturation in the early postnatal life of those
VLBW infants who developed moderate to severe BPD. Although there’s no way to
conclude whether this is the cause of later BPD or it merely reflects more severe lung
disease at the time.
63
Effect of Sildenafil on Alveolarization and Pulmonary Vascular Growth after
Neonatal Treatment with a VEGF Receptor Inhibitor
在接受血管內皮細胞生長激素抑制劑之新生鼠,Sildenafil 對於其肺泡與肺部血管
生長之影響
Yuh-Jyh Lin, Chyi-Her Lin, Chi-Hsien Chien1, Jiu-Yao Wang
Department of Pediatrics and Department of Anatomy1, College of Medicine,
National Cheng-Kung University, Tainan, Taiwan
林毓志、林其和、簡基憲 1、王志堯
國立成功大學醫學院小兒科、解剖科 1
Background: Lung structure in BPD is characterized by decreased alveolar and
vascular growth. Mechanisms that inhibit distal lung growth are poorly understood,
but impaired vascular endothelial growth factor (VEGF) signaling and reduced NO
production can decrease alveolar and vessel growth in the developing lung. NO exerts
its biological activity through stimulating guanosine 3’ ,5’-cyclic monophosphate
(cGMP) production, and cGMP is inactivated by phosphodiesterase (PDE) enzymes.
We hypothesized that use of the cGMP-specific PDE5 inhibitor sildenafil would
promote angiogenesis and improve alveolarization in newborn rats treated with
SU-5416 (VEGF inhibitor).
Methods: Beginning on the second day of life, Sprague Dawley rat pups were
randomly assigned to four groups. The first two groups received single dose of
SU-5416 (20 mg/Kg SC) on day 2 and followed by either sildenafil or placebo
treatment for 2 weeks (SU). The other two groups will receive only single dose of
vehicle (V) for SU-5416 (Carboxymethyl cellulose) on day 2 followed by treatment
with either sildenafil (S) or placebo (P) for 2 weeks. All rats were then killed for
studies, which include measurements of body weight, lung weight, right ventricular
hypertrophy (the ratio of right ventricular to left ventricular plus septum weights;
RV/LV+S), and morphometric analysis of alveolarization (by mean linear intercept;
MLI; radial alveolar counts (RAC); and vascular density).
Results: Compared with vehicle controls, SU reduced body weight (V+P vs SU+P gr.,
51.8+-11 vs 39.8+-5), increased RV index (0.3+-0.1 vs 0.43+-0.11), increased MLI
(35.8+-8.8 vs 52+-5.6), reduced RAC (12.3+-2.4 vs 6.9+-2.3), ND (637+-76 vs
524+-49) and vessel density (22.4+-2.4 vs 8.8+-1.8) in the infant rats. Compared with
SU controls, sildenafil treatment improved distal lung growth, as demonstrated by
increased RAC (SU+P vs SU+S gr., 6.9+-2.3 vs 9.8+-2.1), ND (524+-49 vs 583+-55),
vessel density (8.8+-1.8 vs 17.7+-2.5)and decreased MLI (52+-5.6 vs 42.3+-6.3), RV
index (0.43+-0.11 vs 0.35+-0.12).
Conclusions: SU-5416 retarded alveolar and vascular growth in infant rats. Sildenafil
preserved alveolar and vascular growth and reduced RV hypertrophy in infant rats
treated with SU-5416 during neonatal period.
64
Dextromethorphan Alleviates Apoptotic Damage of Rat Mesencephalic
Dopaminergic Neurons Following Bacterial Lipopolysaccharide Exposure
Dextromethorphan 治療細菌性中腦多巴胺神經細胞凋亡作用機制探討
Yung-Ning Yang, Hsing-I Tseng, Hsiu-Lin Chen, San-Nan Yang1
Division of Neonatology, Department of Pediatrics, Kaohsiung Medical University
Chun-Ho Memorial Hospital; Graduate Institute of Medicine 1, Kaohsiung Medical
University, Kaohsiung, Taiwan
楊詠甯、曾馨誼、陳秀玲、楊生湳 1
高雄醫學大學附設醫院小兒科部新生兒科、高雄醫學大學醫學研究所 1
Background: Bacterial meningitis is still an important infectious disease causing
death and disability. The mortality of bacterial meningitis can reach 30%, and up to
50% of newborn survivors suffer from persisting neurological deficits as a
consequence of the disease as regards learning and memory in later life for the
affected individual. Indeed, perinatal bacteria-induced inflammation in the developing
brain plays an important role in neuronal damage and hence leads to long-term
neurological dysfunction. Here this study determined whether apoptosis of
dopaminergic neurons was involved in the bacterial LPS-mediated neuronal damage
in rat mesencephalic mixed neuron-glia cultures. In addition, dextromethorphan (DM),
an ingredient widely used in anti-tussive remedies, protected dopaminergic neurons
against the LPS-induced apoptotic neuronal damage.
Methods: Sprague-Dawley (SD) rats incorporating a total of 16 dams and their litters
(nine to 11 pups per dam) were housed in the animal-care facility at our institution
and provided with a 12-hr light/dark cycle. The animal numbers used in the present
study were as follows: vehicle-control (n = 30), DM alone (ie test animals receiving
only DM; n = 30), LPS recipients (n = 30), DM plus LPS (n = 30). All experimental
procedures were approved prior to experimental conduct which proceeded in
accordance with the guidelines set by the Animal Care and Use Committee (National
Science Council, Taiwan). At P10, mesencephalic mixed neuron-glia cultures were
prepared from rat pup brains following our previously published protocols.
Immunocytochemical, immunoflourecin and ELISA analyses were applied in this
study.
Results: A 72-hr exposure of LPS (3, 10, or 30 ng/ml) increased not only the
production of tumor necrosis factor (TNFnumber of apoptotic dopaminergic neurons in the mesencephalic cell cultures.
Pretreatment of effective dosage of 3 uM DM (1, 3, or 10 uM) reduced the magnitude
of LPS-induced deleterious effects. The present observations confirmed that
dextromethorphan protects dopaminergic neurons against inflammation-mediated
apoptotic damage, possibly attributed to inhibition of LPS-stimulated TNF-alpha and
NO production, and suggest that DM would have therapeutic efficacy in the treatment
of inflammation-related long-term neurological disorders.
Conclusions: In summary, the present study provides important biomedical evidence
for the notion that bacteria-induced CNS inflammation leads to apoptosis of
mesencephalic dopaminergic neurons through pro-inflammatory factors. More
importantly, this study will explore the possible therapeutic effects resulted from DM,
a clinical available drug with wide safety margin, against such bacteria-induced
apoptosis of mid-brain dopaminergic neurons.
65
A Preliminary Survey on the Decision Making of Pediatricians in Treating
Neonatal Hyperbilirubinemia
兒科醫師對新生兒高黃膽血症處理原則的初步調查
Kuan-Hsieh Lee, Yung-Chieh Lin, Yuh-Jyh Lin, Chyi-Her Lin
Department of Pediatrics, National Cheng Kung University Hospital
李冠賢、林永傑、林毓志、林其和
國立成功大學醫學院附設醫院小兒部
Background: Neonatal hyperbilirubinemia is a common problem for general
pediatric practice. Phototherapy (PT) or blood exchange transfusion (BET) are the
mainstream for treatment. Inappropriate management results in increase risk of
kernicteru, high admission rate and unnecessary BET. Since 2004, hour-specific
guideline for PT or BET was published by American Academy of Pediatrics (AAP).
AAP even introduced an internet online website Bilitool (http://bilitool.org/) to make
it easier to be used. However, policy for treaing hyperbilirubinemia varies among
pediatricians. In this study, we wanted to survey how the pediatricians do in treating
neonatal hyperbilirubinemia.
Methods: A two-paged questionnaire was designed for pediatricians. The
questionnaire included (1) basic information of the pediatrician (2) 5 scenarios of
neonatal jaundice or hyperbilirubinemia , (3) where the guideline they used from and
(4) if they know the AAP guideline and the Bilitool website .The infants in the
scenarios shared the same history but each has a hour-specific serum bilirubin (SB)
level. The scenarios described an active well-hydrated breast-fed term female
newborn with appropriate birth weight, maternal blood type: AB, and non-hemolytic
hemogram. The hour-specific-SB (mg/dL) was given respectively as : 24hrs-8.5 ;
48hrs-14; 72hr-15; 96hr-22; and 168hr-20.5. During interview, doctors can used any
tools, manuals, or plots to finish these questions.
Results: Thirty pediatricians in a university hospital were interviewed. They included
7 (23.3%) visiting staffs, 14 ( 46.7%) junior residents and 9 (30.0%) senior residents.
They used references by 12 (40%) personal empiric experience, 16 (53.3%) by AAP
guideline and 2 (6.7%) by other guidelines. The percentage of those using APP
guidelines was 21 (70.0%) and using Bilitool 16 (53.3%). However, only 6 (20.0%)
completely matched the AAP guideline in the 5 scenarios, and 16 (53%) pediatricians
had different opinions in greater than 2 scenarios when matched with AAP guidelines.
The rate of blood exchange (BET) in each scenario was 0%, 0%, 0%, 16.7%, and
13.3%, respectively, though none of these need BET if by AAP guideline with lower
risk.
Conclusions: Majority (70%) of pediatrician knew AAP guidelines of treating
neonatal hyperbilirubinemia, but 40% of them make their judgment by personal
experience. Although 53.3% doctors declared that they followed AAP guideline, yet
only 20% truly make it. This finding indicates that new strategies should be
implemented to encourage pediatricians to follow AAP guideline in treating neonatal
hyperbilirubinemia.
66
The Expression and Functional Assay of Toll-Like Receptors from Monocytes in
Premature Infants
早產兒單核球類鐸受器的表現及功能測定
Chung-Min Shen
Department of Pediatrics, Cathay General Hospital;Institute of Clinical Medicine,
National Yang-Ming University
沈仲敏
國泰綜合醫院小兒科、國立陽明大學臨床醫學研究所
Background: Premature newborns are highly susceptible to severe bacterial
infections. The expression of Toll like Receptors (TLRs) and the possible involvement
of innate immunologic deficiencies of the premature infants have not been extensively
investigated. The aim of this study was to evaluate TLR2 and TLR 4 expressions from
preterm infants, health full term newborns and adults.
Methods: Adult healthy volunteers (n = 10; mean age, 27 ± 0.3 years old; male, 60 %;
female, 40 %) were included for collection of peripheral blood. Health full term
infants (n = 30; mean gestational age, 38.8 ± 0.8 wks; birth body weight, 3224.2 ±
301.45 gm; male, 40.7 %; female, 59.3 %) and preterm newborns ( n = 8; mean
gestational age, 31.4 ± 2.5 wks; birth body weight 1782.3 ± 309.8 gm; male, 65.6 %;
female, 34.4 %) were included for collection of cord blood immediately after delivery.
We collected the PBMC for the following analysis: (a) Expression of TLR 2 and
TLR4 including the surface and intra-cellular protein will be detected by flow
cytometry and TLR2 and TLR4 mRNA levels will be quantified by real time-PCR. (b)
The production of IL-1β, IL-6, and TNF-α cytokines will be determined by ELISA
after monocyte stimulation with LPS to evaluate functional assay.
Results: The expression of TLR2 and TLR4 including cell surface and intra-cellular
protein, detected by flow cytometry were significantly reduced in comparison to full
term infants and to adults. The mRNA level of TLR2 and TLR4 were lower in
premautre infants, too. Besides, the production of IL-1β, IL-6, and TNF-α after LPS
stimulation were lower in premature infant.
Conclusions: The protein and functional expressions of TLR2 and TLR4 were lower
in premature infants than full term and adults. It indicated the impairement of innate
immune system in premature infants.
67
The Notch Pathway Plays a Role in Experimental Sepsis
Notch 訊息在敗血症動物模式中扮演的角色
Po-Nien Tsao1, Shu-Chen Wei2, Miao-Tzu Huang3, Hung-Chieh Chou1, Chien-Yi
Chen1, Wu-Shiun Hsieh1
Departments of 1Pediatrics, 2Internal Medicine, 3Medical Research, National Taiwan
University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
曹伯年 1、魏淑珍 2、黃妙慈 3、周弘傑 1、陳倩儀 1、謝武勳 1
台灣大學附設醫院 1 小兒部, 2 內科部, 3 醫研部
Background: Notch signaling is a highly-conserved pathway involved in cell fate
decisions, proliferation and survival. In the immune system, the role of Notch
signaling in the development and function of macrophages, NK cells, T cells, B cells
and dendritic cells has been reported. However, the role of Notch signailing in the
pathogenesis of sepsis is unclear.
Methods: We investigated the expression patterns of Notch components in LPS
stimulated murine macrophage cell line by real-time PCR and Western blots and the
role of gamma-secretase inhibitor, a potent Notch inhibitor, in LPS induced cytokine
release and experimental sepsis.
Results: Notch pathway components were expressed in murine macrophages and it
was activated after LPS stimulation. By pharmacological approach to inhibit or
exogenous soluble ligands to activate Notch signaling, we show LPS-induced Notch
activation amplifies the inflammatory response to LPS stimulation in macrophages.
Treatment with gamma-secretase inhibitor attenuated inflammatory responses and
improved survival in cecal ligation and puncture (CLP)-induced sepsis model.
Conclusions: These findings support a synergistic effect of Notch signaling and LPS
pathway both in vitro and in vivo. Notch inhibitor may therefore have utility as an
adjunctive agent for the treatment of sepsis syndrome.
68
Tc-99m-HL91 : Early Detection of Hypoxic-Ischemic Brain Injury in a Newborn
Rat Model
Tc-99m HL91: 早期偵測新生鼠腦部缺氧缺血傷害
Bi-Fang Lee1, Nan-Tsing Chiu1, Chao-Ching Huang2, Chien-Chung Hsia3, Lie-Hang
Sheng3
Departments of Nuclear Medicine (B.-F. L., N.-T. C.)1, and Pediatrics (C.-C. H.)2,
National Cheng Kung University, College of Medicine and Hospital, Tainan, Taiwan
3
Institute of Nuclear Energy (C.-C. H., L.-H. S.), Lungtan, Taiwan
李碧芳 1、邱南津 1、黃朝慶 2、夏建忠 3、沈立漢 3
1
. 成大醫院核醫科 2.成大醫院小兒科 3.核研所
Background: The aim of this study is to investigate the value of Tc-99m-HL91
imaging as an early biomarker in a neonatal asphyxia model of the newborn rats.
Methods: The animal neonatal asphyxia model was established. These pups were
divided into three groups: control, hypoxia only, and hypoxia-ischemia groups. All of
these three groups received the identical experimental protocols that included
Tc-99m-HL91 imaging in vivo and ex vivo, TTC staining, and quantitative
autoradiography.
Results: After 2.5 hours after hypoxia-ischemia insult, the pups of the
hypoxia-ischemia group had significantly high Tc-99m-HL91 uptake ratio over the
brain hypoxia-ischemia region. The uptake ratios, although variable, were decreased
by 44 hours after hypoxia-ischemia insult. Both autoradiograms and TTC staining of
brain sections demonstrated avid Tc-99m-HL91 uptake in brain hypoxia-ischemia
areas. As for the optimal imaging time for Tc-99m-HL91 imaging after single bolus
injection, it is suggested 1 to 4 hours after administration.
Conclusions: Tc-99m-HL91, an hypoxia-imaging agent, could be as an early
biomarker of brain hypoxia-ischemia areas in a rat neonatal asphyxia model.
69
Infantile Hypertrophic Pyloric Stenosis:comparison of pyloromyotomy with
medical treatment using atropine sulfate
比較幽門切開術及 Atropine sulfate 治療在先天幽門狹窄的運用
Ying Lin, Hsiang-Yu Lin, Yu-Lung, Hsu, Bai-Horng Su
Department of Pediatrics, China Medical Hospital , Taichung, Taiwan
林瑩、林湘瑜、許玉龍、蘇百弘
中國醫藥大學附設醫院兒科部
Background: Infantile hypertrophic pyloric stenosis(IHPS) is the most common
surgical condition affecting young infants. Currently surgical operation
(Fredet-Ramstedt’s pyloromyotomy) is the standard treatment. Medical treatment with
Atropine sulfate is an alternative treatment in IHPS.
Methods: From January 2001 to December 2008, infants with of IHPS admitted at
China Medical University Hospital were retrospectively reviewed. The diagnosis was
confirmed by abdominal sonogram. Thirteen infants received surgical treatment, and
eight infants received atropine sulfate. Atropin sulfate treatment started with IV form
(0.01mg/kg,IVD, 5 minutes) and then changed to oral form( 0.02mg/kg) before each
meals, and discontinued while reaching full feeding without vomiting. The characters
of the patients, the effect and complication of the treatment, and the cost of the two
groups were compared with each other.
Results: Two groups were matched for clinical criteria with ultrasound and
physiological status on admission. Atropine treatment was tolerated well (with
temporary side effect of tachycardia or facial flash) and effective in all subjects
without refractory cases. One case of pyloromyotomy was complicated with duodenal
perforation and the rate of post-op ICU care was 46%. The average time taken to full
feeding (120ml/kg/d) without vomiting was 4.5 ± 2.9(range, 2 to 9) days in the
atopine group and 4.0 ± 2.8 (range, 1 to 11) days in the pyloromyotomy group (P=0.7).
The length of hospitalization was 10.5 ± 5.3 (range, 5 to 18) days in the aropin group
and 7.8 ± 4.7(range, 4 to 19) days in the pyloromyotomy group(P=0.2). Total costs
were lower in the atropine group and more expensive in the pyloromyotomy
group.(NTD: 41,930 vs 69,132 P=0.03)
Conclusions: Atropine sulfate treatment is an effective safe and less invasive
treatment for IHPS. Considering the current medical and healthy care insurance
system, atropine sulfate treatment may be considered as an alternate for
pyloromyotomy in the treatment of IHPS.
心臟血管學
70
Evaluation of Arterial Wall Function Using Auto-Tracking Sonographic Method
動脈管壁功能解析-以自動血管內膜追蹤新法之研究
Jia-Kan Chang, Chi Chen1, Yong-Hwa Hsu1, Chu-Chung Lin2, Ta-Cheng Huang2,
Ken-Pen Wong2, Kai-Sheng Hsieh2
Department of Pediatrics, Cheng-Hsin General Hospital, Taipei, Section of
Cardiology and Critical Care, Children’s Hospital Hu-Nan, China1, Veterans General
Hospital, Kaohsiung, Taiwan2
張嘉侃、陳智 1、徐詠華 1、林竹川 2、黃大誠 2、翁根本 2、謝凱生 2
台北振興醫院小兒科；湖南兒童醫院心臟及重症科 1；高雄榮民總醫院兒童醫學
部2
Background: Arterial wall parameters during atrial-ventricular coupling process for
each cardiac cycle are important determinants of cardiac performance. We have
previously reported our experience of evaluation of arterial wall characteristics using
a specialized blood pressure measurement system. Recent advance in imaging has
allowed the evaluation of arterial function with sonography. The ability of
visualization of the arterial wall luminal changes dynamically using the ultrasound
technique could be studied.
Methods: In December 2008, we have evaluated the brachial arterial wall in 20
children using a novel electronic technique. The novel technique consists of a
sonographic imaging system capable of displaying the sonographic image of the
arterial wall then automatically electronically tracks the endothelial signals after
setting the interesting zones thus automatically generating the diameters and the
changes of the diameters during each cardiac cycle. With this novel technique, the
flow-mediated dilatation (FMD) of the brachial artery was performed and recorded for
further analysis.
Results: The mean age of children was 11.8 years; none of children had clinical
evidence of arteriosclerosis. The baseline brachial arterial diameters were 3.37 cm at
systole and 3.29 cm at diastole. The peak diameter after luminal compression was
3.63 cm at systole and 3.56 cm at diastole. The resulting luminal change of FMD was
8.51% at systole and 8.85% at diastole. None of these children had evidence of
intimal thickening or irregularity.
Conclusions: Our evaluation of FMD using the novel automatic e-tracking method
established a new tool for study of arterial wall function. With the advantage of
automatic endothelial border tracking, the new technique avoids the possible error
from human measurement for relatively small-sized peripheral arterial dimensions.
This pilot evaluation provides a normal range for arterial wall function using the new
e-tracking technique.
心臟血管學
71
Increased Persistent Microvolt T-wave Alternans by Modified Moving Average
Beat Analysis in Repaired Tetralogy of Fallot
在法洛氏四重症完全矯正後以修正移動平均波分析微 T 波變異度有增加情形
Shuenn-Nan Chiu, Jou-Kou Wang, Ming-Tai Lin, En-Ting Wu, Chun-An Chen,
Chun-Wei Lu,, Hung-Chi Lue, Mei-Hwan Wu
Department of Pediatrics, National Taiwan University Hospital
邱舜南、王主科、林銘泰、吳恩婷、陳俊安、盧俊維、呂鴻基、吳美環
台大醫院小兒部
Background: Microvolt T wave alternans (MVTA) has been shown as a marker for
increased risk of arrhythmia in adults with ischemic or dilated cardiomyopathy. Its
implication for risk stratification in patients with tetralogy of Fallot (TOF) is still
unclear.
Methods: Treadmill examination by Bruce protocol with modified moving average
beat analysis of MTWA was performed in 64 patients (43 males and 21 females) with
repaired TOF. In addition, data from 118 age- and sex- matched children and
adolescents with normal cardiac structure served as controls. MTWA that persisted
longer than 2 minutes (pMTWA) was counted as valid. At measuring the pMTWA, we
used 125 bpm as threshold heart rate for those older than 15 years old and 67% of
predicted maximal heart rate for those younger than or equal to 15 years old.
Results: The age of TOF patients at latest followreceived
Rastelli conduit operation in 42 (65.7%) and valve sparing surgery in 21 (32.8%) for
right ventricular outflow reconstruction. Conclusive pMTWA was achieved in 58
patients. We found that the pMTWA values were much higher in TOF patients than in
sex and the QRS duration of EKG. By using 28uV as a cut point value, positive
MTWA was found in only 4% of the control. In TOF patients, 9 (14.1%) experienced
late arrhythmic events at a mean followto have positive MTWA (5/9 versus 10/49, p=0.041). By logistic regression analysis,
prolonged QRS duration and positive MTWA were two independent risk factors of
late arrhythmic events in TOF patients.
Conclusions: MTWA measured by modified moving average beat analysis may be a
useful marker to predict late arrhythmic events in TOF patients, other than prolonged
QRS duration.
心臟血管學
72
Outcomes and Risk Factor of Intensive care after Arterial Switch Operation for
d-Transposition of great arteries
完全性大動脈轉位症進行大動脈轉換手術的術後的照護及相關危險因子
Ya-Mei Chang1,2, En-Ting Wu1, Sheunn-Nan Chiu1, Shu-Chien Huang3, Ching-Chia
Wang1, Chun-An Chen1, Ming-Tai Lin1, Yih-Sharng Chen3, Jou-Kou Wang1,
Mei-Hwan Wu1
1.Departments of Pediatrics , National Taiwan University Hospital and College of
Medicine, National Taiwan University, Taipei, Taiwan 2.Department of Pediatrics,
Taipei City Hospital – Branch for Women and Children,Taipei, Taiwan 3.Departments
of Surgery, National Taiwan University Hospital and College of Medicine, National
Taiwan University, Taipei, Taiwan
張亞玫 1,2、吳恩婷 1、邱舜南 1、黃書健 3、王景甲 1、陳俊安 1、林銘泰 1、陳益
祥 3、王主科 1、吳美環 1
1. 國立台灣大學附設醫院小兒部 2. 台北市立聯合醫院婦幼院區 3. 國立台灣
大學附設醫院外科部
Background: To describe the outcome after arterial switch operation for transposition
of great arteries (TGA) and the factors related to mortality and length of ICU stay and
ventilator days after arterial switch operation.
Methods: All 57 patients of d-TGA who received arterial switch operation during
January 2003 to December 2008 were enrolled. Charts were retrospectively reviewed,
and intensive care unit (ICU) stay duration, intubation days, and immediate mortality
were recorded, and risk factors including prematurity, heart status, and preoperative
procedure were analyzed.
Results: During 2003 to 2008, there were 57 patients of TGA admission to SICU after
arterial switch operation. The median age was 7days (1-179) and the body weight at
operation was 3.2kg (1.3-5.7). For associated lesions, 6 patients (9%) combined with
coarctation of aorta (COA) or interrupted aortic arch, 21 cases (37%) has ventricular
septal defect (VSD), and 30 cases (53%) had usual coronary artery pattern. The early
survival rate was 87.7%.Medium of ventilator days and length of ICU stay was 7 days
(3-135) and 12days (2-140), respectively. Patients with body weight less than 3kg and
gestation age <37wks has higher risk of length of ventilator days, ICU stay and ICU
mortality (25% vs 5%). Abnormal coronary artery pattern was not associated with
ICU mortality and ICU stay, but patients combined VSD had longer ventilator days
and combined COA had longer hospital stay (p<0.01). Patients receiving balloon
atrioseptostomy before operation had shortened ventilator and ICU stay length. The
late mortality occurred in three patients, and the one year and five year survival were
87.2% and 80% by K-M analysis after follow-up 135 patient-years.
Conclusions: The mortality rate of d-TGA patient who received arterial switch
operation is 12.3%. Lower body weight (<3kg) and prematurity has higher risk of
length of ventilator days, ICU stay and ICU mortality.
心臟血管學
73
Genetic Polymorphisms of Cytokines and Susceptibility to Kawasaki Disease in
Taiwanese Children
八種細胞激素基因多型性和台灣川崎氏症病童的相關性
Ken-Pen Weng1,2, Ya-Hui Chiao4, Jin-Tsuey Cheng4, Yu-Tung Huang1, Shih-Hui
Huang3, Chu-Chuan Lin1, Tsyr-Yuh Ho2, Tsung-Jen Lai4, Luo-Ping Ger1, Kai-Sheng
Hsieh1
Ken-Pen Weng1,2, Ya-Hui Chiao4, Jin-Tsuey Cheng4, Yu-Tung Huang1, Shih-Hui
Huang3, Chu-Chuan Lin1, Tsyr-Yuh Ho2, Tsung-Jen Lai4, Luo-Ping Ger1,4,
Kai-Sheng Hsieh1 Department of Pediatrics and Medical Education and Research,
Kaohsiung Veterans General Hospital1;Department of Pediatrics, Zuoying Armed
Forces Hospital2; Department of Nursing, Fooyin University3; Institute of
Biomedical Sciences, National Sun Yat-Sen University4, Taiwan
翁根本 1,2、喬雅惠 4、陳錦翠 4、黃御統 1、黃世惠 3、林竹川 1、何慈育 2、賴琮
仁 4、葛魯蘋 1、謝凱生 1
高雄榮民總醫院兒醫部, 教研部(1) 國軍左營醫院小兒科(2) 輔英科技大學護理
科(3) 中山大學生醫所(4)
Background: Kawasaki disease (KD), an acute systemic vasculitis with a predilection
for Asian race, occurs mainly in infants and children under 5 years of age. The
etiology of KD remains unknown and may be attributed to the combined effects of
infection, immune response, and genetic susceptibility. Acute KD is associated with
systemic immune activation, including elevated serum levels of IL-1, IL-4, IL-10, and
a variety of other cytokines that may be involved in the pathogenesis of KD. This
study aimed to investigate the association of eight various polymorphisms of five
inflammation-related genes (IL-1A, IL-1B, IL-1RN, IL-4, IL-10) with KD.
Methods: A total of 216 children with KD and 226 hospital-based healthy adult
controls were included in this study. Genomic DNA was extracted from buffy coat
samples. The polymorphisms of IL-4 intron3 VNTR, IL-1 RN intron2 VNTR, IL-1A
C-889T, IL-1B T-31C, IL-1B C-511T, IL-4 T-590C, IL-10 A-592C, and IL-10 T-819C
were determined by PCR.
Results: There were no statistically significant differences between the eight
polymorphisms and risk of KD, either in the single locus genetypic analysis or
multiple loci haplotypic analysis. In the combined analysis from eight polymorphisms,
subjects (51 KD children and 30 healthy controls) with greater than or equal to three
“at risk” genotypes had higher risk of KD as compared to those (165 KD children and
196 healthy control) with less than three “at risk” genotypes ( AOR=2.70; 95% CI:
1.26-5.80; P=0.011).
Conclusions: In conclusion, the combined analysis demonstrated the association
between genetic polymorphisms of cytokines and KD, except the single locus
genetypic analysis or multiple loci haplotypic analysis.
心臟血管學
74
Hybrid therapy for hypoplastic left heart syndrome
融合治療左心發育不全症
Yun-Ching Fu, Hao-Ji Wei1, Ming-Chih Lin, Sheng-Ling Jan
Division of Pediatric cardiology and cardiovascular surgery﹛1﹜, Taichung Veterans
General Hospital; Taichung, Taiwan
傅雲慶、魏皓智 1、林明志、詹聖霖
台中榮民總醫院小兒心臟科、心臟血管外科﹛1﹜
Background: Norwood or Sano operation is the traditional treatment for hypoplastic
left heart syndrome. However it carries high risks of mortality and complications.
Here we report the first case experience of hybrid therapy in Taiwan.
Methods: The 4-day-old boy was referred to our hospital due to sudden onset of
cardiopulmonary collapse s/p cardiopulmonary resuscitation. On admission, he
presented cardiopulmonary failure with bloody stool and hematuria.
Echocardiography showed hypoplastic left heart syndrome, mitral atresia, severe
aortic stenosis, hypoplastic ascending aorta, patent foramen ovale and small patent
ductus arteriosus of 0.19 cm. After infusion of prostaglandin and inotropic agents, the
vital signs recovered. Hybrid therapy including banding of bilateral pulmonary
arteries and stenting of patent ductus arteriosus was done at the age of 10 days.
Balloon atrial septostomy was performed at the age of 11 days.
Results: The cardiopulmonary failure significantly improved after hybrid therapy.
The patient thrived well to 2 months old with body weight of 4.4 kg. He was
discharged and waiting for stage II operation.
Conclusions: Our limited experence indicates that hybrid therapy is a good
alternative therapy for hypoplastic left heart syndrome especially in the neonate with a
poor clincial condition.
75
Age at Respiratory Viral Infection Determines the Subsequent Allergic
Responses in Mice
小鼠呼吸病毒感染時的年齡可決定之後致敏反應的強弱
Shen-Hao Lai1, Sui-Ling Liao2, Antonieta Guerrero-Plata3, Deepthi Kolli3, Antonella
Casola3, Roberto P. Garofalo3
Department of Pediatrics, Linkou Chang Gung Memorial Hospital 1, Department of
Pediatrics, Keelung Chang Gung Memorial Hospital 2, Department of Pediatrics,
University of Texas Medical Branch, Galveston TX 3
賴申豪 1、廖穗綾 2、Antonieta Guerrero-P3、Deepthi Kolli3、Antonella Casola3、
Roberto P. Garofalo3
林口長庚醫院兒童內科部 1，基隆長庚醫院小兒科 2，Department of Pediatrics,
University of Texas Medical Branch, Galveston TX 3
Background: Epidemiological and animal studies show that respiratory viral
infection in early life can modulate subsequent development of asthma. Under the
exposure of foreign antigen, age-dependent immune responses launched by youngster
have already been observed. Human metapneumovirus (hMPV) is among the
commonest pathogens of respiratory infection in young children. Its role in the
manipulation on development of allergic diseases is seldom investigated. We want to
to elucidate the effect of hMPV infection on the subsequent development of allergic
asthma, and clarify if this effect is modified by age at infection.
Methods: Weanling and newborn BALB/c mice are infected with hMPV, and then
immunized/challenged with ovalbumin (OVA) after their recovery from disease. One
day later, we analyze Th2 responses and inflammation in lung, OVA-specific antibody
production in serum, and lymphoproliferation ex vivo.
Results: hMPV infection in weanling suppresses the OVA-evoked airway
eosinophilia, airway hyperresponsiveness, mucus hyperproduction, and peribronchial
inflammation. These findings correlate with decreased levels of Th2 cytokine (IL-4, 5,
and 13), eosinophil-trophic chemokine (eotaxin, RANTES, MCP-1, GM-CSF,
MIP-asthma responses link to the increased
frequency of INF- -producing CD4 cells and attenuated OVA-induced
lymphoproliferation. But all these anti-asthma effect can’t happen to mice inoculated
with hMPV at newborn.
Conclusions: Age at hMPV infection plays a critical role in the suppression of
subsequent asthma development. Studies involving “hygiene hypothesis” should take
the factor of age into consideration
76
Usefulness of transthoracic ultrasound for the diagnosis of acute chest disease in
pediatrics
超音波運用於兒童急性肺部疾病診斷之經驗
I-Chen Chen1, Zen-Kong Dai1, Chien-Ming Tseng1, Jong-Hau Hsu1, Jiunn-Ren Wu2
Department of Pediatrics, Kaohsiung Medical University Hospital1、Department of
Pediatrics, Kaohsiung Municipal Hsiao-Kang Hospital2
陳怡真 1、戴任恭 1、曾建銘 1、徐仲豪 1、吳俊仁 2
高雄醫學大學附設醫院兒科 1 、高雄市立小港醫院兒科 2
Background: Transthoracic ultrasound (US) has become an established imaging tool
in the evaluation of children in a variety of conditions. Our object is to assess the
diagnostic potential of transthoracic US in acute chest disease in pediatrics.
Methods: This is a prospective study in a tertiary medical center. Children aged from
1 month to 18 years with clinical signs suggestive of pulmonary disease underwent
transthoracic US and CXR. The characteristics of various chest diseases were
analyzed according to (1) margin of the lesion (2) internal echogenecity (3) fluid
bronchogram (4) air bronchogram (5) “gliding sign” of the pleural line (6) comet tail
artifacts (7) pleural effusion and/or pericardial effusion and (8) pleural thickening.
Results: Transthoracic US provided images in 62 patients, detecting 41 pneumonias,
3 pneumothraox, 12 pleural effusions, 2 pericardial effusions (one cardiac tamponade),
and 1 congenital pulmonary malformation. There were 30 cases with air
bronchograms, 12 cases with fluid bronchograms, and 28 cases with multiple
comet-tails artifacts, which suggest acute alveolar interstitial syndrome. Chest X-ray
was provided in all patients and CT in 5 patients. The detect ability of transthoracic
US was higher than traditional CXR in certain circumstances and the advantages of
this imaging modality will be discussed in detail.
Conclusions: Transthoracic US is a rapid, easily available, cost-effective, minimally
invasive tool, without ionizing radiation, and has great potential in many pediatric
chest queries. Pediatric pulmonologist should be familiar with this technique in
treating the pediatric patients with acute respiratory disorders
77
Effects of Activated Protein C on Ventilator-Induced Lung Injury in Rats
活化蛋白質 C 對老鼠之呼吸器導致肺損傷的作用
Chung-Ming Chen1, Hsiu-Chu Chou2, Leng-Fang Wang3, Yaw-Dong Lang4
Department of Pediatrics1, Anatomy2, Biochemistry3, and Graduate Institute of
Medical Sciences4, Taipei Medical University, Taipei, Taiwan
陳中明 1、周綉珠 2、汪棱芳 3、藍耀東 4
台北醫學大學小兒學科 1、解剖學科 2、生化學科 3、醫學科學研究所 4
Background: Increased procoagulant activity and alveolar fibrin deposition are
pathognomonic features of ventilator-induced lung injury (VILI). Our previous study
found increased local and systemic plasminogen activator inhibitor-1 (PAI-1) in VILI.
The aims are to investigate the effects of activated protein C (APC), an anticoagulant
by inhibiting PAI-1 activity, on local and systemic fibrinolytic activity in VILI and to
find a potential treatment modality.
Methods: The Sprague-Dawley rats were ventilated with a high-volume zero PEEP
(HVZP) protocol by a volume-cycled ventilator for 2 h at a tidal volume of 30 mL/kg,
a respiratory rate of 25 breaths/min, and an FiO2 of 0.21. Fifteen minutes before
ventilation, the rats received either intravenous APC (250 μg/kg, HVZP+APC group)
or normal saline (HVZP group). Another group that received no ventilation served as
the control.
Results: The arterial blood gas tensions were comparable among three study groups.
Total protein and macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar
lavage fluid (BALF) were significantly higher in rats ventilated with HVZP protocol
than in control and HVZP+APC groups. HVZP + APC group tends to decrease BALF
protein compared with HVZP group (P = 0.07). PAI-1 mRNA expression significantly
increased in rats ventilated with the HVZP and HVZP + APC protocols than in control
animals. Compared to control group, rats treated with HVZP ventilation demonstrated
significantly higher plasma PAI-1 levels. HVZP + APC group tended to have lower
PAI-1 than did the HVZP group (P = 0.069). Rats treated with HVZP ventilation
exhibited significantly higher plasma D-dimer than did the control group. The plasma
level of D-dimer measured for HVZP + APC group was indistinguishable from that of
control group. Very few fibrin is detected in HVZP + APC group.
Conclusions: Pre-administration of APC at a dose of 250 μg/kg demonstrates
anti-inflammatory and anti-coagulant activity and decreases alveolar fibrin deposition
in VILI.
78
Influenza B-associated rhabdomyolysis in Taiwan children
B 型流行性感冒併發橫紋肌溶解症
Chang-Teng Wu, Jing-Long Huang, Jainn-Jim Lin, Shao-Hsuan Hsia
Department of Pediatrics, Children Medical Center, Chang Gung Memorial Hospital,
Chang Gung University College of Medicine, Tauyuan, Taiwan
吳昌騰、黃璟隆、林建志、夏紹軒
長庚醫院兒童醫學中心兒童內科部兒童加護科
Background: Influenza B-associated rhabdomyolysis (IBAR) is an infrequent and
poorly known complication of influenza B virus infection in children. Diagnosis is
usually made by the clinical history, presence of influenza in the community, and by
detecting influenza virus in nasopharyngeal specimens. The aim of this study was to
describe the clinic and laboratory manifestations, complication and outcomes of IBAR
in Taiwan children.
Methods: We conducted a retrospective analysis of cases aged less than 17 years of
IBAR diagnosed at university children’s hospitals in North Taiwan during 8-year
periods (2000-2007). All children enrolled in the study had presented with
rhabdomyolysis due to laboratory-confirmed influenza B infection. Findings were
included demographic data, clinical manifestations, complications and outcome.
Results: Overall, 24 IBAR cases were analyzed. IBAR typically occurred in
school-aged children with a 7:3 male predominance. The mean age is 7.2+ 1.9. Nearly
63% of cases were between 6 and 9 years old. The median interval between onset of
influenza and onset of IBAR was 3.4 days (range 1–14). The calf muscles were
involved in 96% of cases. Laboratory tests showed the mean initial blood creatine
phosphokinase (CPK) was 4212 U/L. Median duration to clinical recovery was 5 days
(range 1–24). No patient had renal failure and received dialysis..
Conclusions: IBAR tends to occur mainly in winter and spring during influenza B
outbreaks. IBAR sometimes induce renal failure. Early detection and careful medical
treatment is necessry. In this study, the outcomes of IBAR are good after medical care.
79
Early Elevations in B-type Natriuretic Peptide Levels Are Associated with Poor
Clinical Outcomes in Pediatric Acute Lung Injury
兒童急性肺損傷時早期升高之 B 型利鈉胜肽與其不良預後相關
Jong-Hau Hsu1, 2, Bhupinder Reel2, Peter Oishi2, Heidi Flori2, Zen-Kong Dai1,
Jiunn-Ren Wu1, Jeffrey Fineman2
1
Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung,
Taiwan, and 2Department of Pediatrics, University of California, San Francisco,
California, USA
徐仲豪 1, 2、Bhupinder Reel2、Peter Oishi2、Heidi Flori2、戴任恭 1、吳俊仁 1、Jeffrey
Fineman2
高雄醫學大學附設醫院小兒科 1 及美國舊金山加州大學小兒科 2
Background: Acute lung injury (ALI) and the acute respiratory distress syndrome
(ARDS) cause significant morbidity and mortality in children. Impaired
cardiopulmonary interactions may contribute to the pathophysiology. B-type
natriuretic peptide (BNP) is an established biomarker for adult congestive heart failure,
but the potential utility for BNP in the management of pediatric patients with
ALI/ARDS has not been studied. We hypothesized that BNP levels would be
increased in children with ALI/ARDS and would predict poor clinical outcomes.
Methods: Plasma BNP levels were measured by immunoassay on day 1 of ALI in 50
pediatric patients. Associations between BNP levels and outcome were determined.
Results: The mean PaO2/FiO2 at the onset of ALI was 155 (± 74) and BNP values
ranged from 5 to 2060 pg/ml with a mean of 109 (± 311). BNP levels were inversely
correlated with ventilator-free days (Spearmen rho - 0.30, p=0.04), and positively
correlated with exhaled tidal volume (Spearmen rho 0.44, p=0.02). BNP levels were
higher in patients receiving inotropic support than patients not receiving inotropic
support (p=0.02). BNP levels were correlated with PRISM III scores (Spearmen rho
0.55, p<0.001) and PELOD scores (Spearmen rho 0.4, p=0.006). BNP levels were
higher in non-survivors (n=9) than survivors (n=41, p <0.01)
Conclusions: BNP levels are elevated in children with ALI/ARDS early in the disease
course, and increased levels are associated with worse clinical outcome.
80
Prolonged Methylprednisolone Therapy in Unresolving Acute Respiratory
Distress Syndrome in Children
類固醇(Methylprednisolone)的使用在兒童未緩解之急性呼吸窘迫症候群的效果
Shen-Dar Chen1, Jieh-Neng Wang2, Wen-Ping Hung2, Hok-Keong Chang3,
Ching-Chuan Liu2, Jing-Ming Wu2
Departments of Pediatrics, Chia-Yi Christian Hospital 1 National Cheng Kung
University Hospital 2 Sin Lau Hospital Madou Branch 3
陳聖達 1、王玠能 2、洪文品 2、鄭福強 3、劉清泉 2、吳俊明 2
嘉義基督教醫院小兒科 1 國立成功大學醫院小兒科 2 新樓醫院麻豆分院小兒
科 3
Background: The managements of pediatric acute respiratory distress syndrome
(ARDS) are still very difficult. No pharmacological therapeutic protocol has been
found effective in modifying the clinical course of acute respiratory distress
syndrome.
Methods: Patients with ARDS were managed with conventional treatments in the
pediatric intensive care unit (PICU) of the National Cheng Kung University Hospital.
However, a prolonged methylprednisolone treatment protocol was considered in
patients who did not response well after 7 days of intubation. The protocol was briefly
as a loading dose of 2 mg/kg followed by 2 mg/kg per day from day 1 to day 14,
1mg/kg per day from day 15 to day 21, 0.5 mg/kg per day from day 22 to day 28, 0.25
mg/kg per day on days 29 and 30, and 0.125 mg/kg per day on days 31 and 32. We
retrospectively reviewed the medical records of these patients. Clinical parameters
and outcome were recorded.
Results: From January 2007 to November 2008, there were four patients (age range
from 2 months to 8 yr 1 mo) enrolled in this study. The mean days of
methylprednisolone use after intubation were 11 days. The mean days of extubation
after methylprednisolone use were 9.75 days. The oxygen index improved obviously
after methylprednisolone treatment. All patients were survived and discharged.
Conclusions: According to our current results, prolonged administration of
methylprednisolone in patients with unresolving ARDS was associated with
improvement in oxygen index and outcome.
81
The effect of BiPAP Ventilation via Tracheostomy Tube for Children with chronic
respiratory Failure
---- the role of added the 3rd pole in one way tube
兒童慢性呼吸衰竭經氣切管給予雙階陽壓通氣的療效--呼吸管增加第三開口的
角色
Teh-Ming Wang
Department of Pediatrics,Taichung-Veterans General Hospital
王德明
臺中榮總兒童醫學部
Background: Bilevel positive airway pressure (BiPAP) has become a widely used
procedure to support patients with respiratory failure, both in the chronic and acute
settings. Recently, the mode of ventilation has been extended to the pediatric patients.
However, BiPAP ventilation via tracheostomy tube for the treatment of children with
chronic respiratory failure has never been reported before. Therefore, we present our
preliminary report here.
Methods: 1.Between Mar 2004 and Dec. 2007,six of nine patients underwent
trachostomy owing to prolonged ventilator support (>4 weeks) and couldn’t be
weaning from CMV in a short time enrolled to this study. 2.They were shifted from
CMV to ViPAP ventilator (ResMed, Autralia) on Day 7-11 post tracheostomy. 3.
Clinical and laboratory variables immediately prior to ViPAP and 1- 4 hours after
institution, and 1- 4 hours after add 3rd pole on BiPAP circuit were evaluated. 4. The
outcome was depended on whether patients could tolerate ViPAP support through
tracheostomy.
Results: There were 6 patients met the inclusiopn criteria. The mean age was 83
months old, 35 to 192 months old. The male was predominant(M:F=2:1). All the six
patients were failed with ViPAP support initially but they could tolerate well with
ViPAP support after added the 3rd pole to the one way tube except one. All the
patients'' ventilation parameters got exacerbated while the ventilation mode was
shifted from CMV to BiPAP initially,raising PaCO2 level, increased respiratory rate,
decreased O2 saturation. But they were all improved while added the 3rd pole on the
one way ventilatory tube without any ventilatory complications, such as
pneumothorax and patients could go home with BiPAP home ventilator care except
one.
Conclusions: 1.ViPAP ventilation via tracheosotomy tube is effective and safe
method for respiratory assistance in pediatric patients with respiratory insufficiency or
failure. 2. It is the key factor to add the 3rd pole on the one way tube for pediatric
patients with chronic respiratory insufficiency or failure successfully supported by
ViPAP.
82
Is Weekly Change of Tubing Really Matter for Ventilator Associated Pneumonia?
每週更換呼吸器管路有助於預防呼吸器相關之肺炎嗎？
Ming-Chih Lin1, Mi-Shu Huang2, Po-Yen Chen3, Sheng-Ling Jan1, Yun-Ching Fu1
Pediatric Intensive Care Unit, Department of Pediatrics 1 Department of Nursing 2
Division of Pediatric Infection 3 Taichung Veterans General Hospital
林明志 1、黃彌淑 2、陳伯彥 3、詹聖霖 1、傅雲慶 1
台中榮民總醫院 兒童醫學部 兒童加護中心 1 台中榮民總醫院 護理部 2 台中榮
民總醫院 兒童醫學部 兒童感染科 3
Background: Ventilator associated pneumonia (VAP) contributes to a significant
portion of nosocomial infection in critical patients. It carries certain mortality and
morbidity in modern intensive care units. Ventilator tubing hygiene is always
considered a risk actor. However, whether routine maintenance of ventilator circuits
can prevent VAP or not is still a controversial topic. Thus, we performed a
retrospective study to see if weekly changes of the circuit help in preventing VAP.
Methods: This is a retrospective cohort study. From Nov. 2007 to Dec. 2008, all
charts of patients admitted to a pediatric intensive care unit were reviewed. Patients
were enrolled if they have records of using ventilators. VAP cases were defined by the
record of the institution’s infection control committee. Patients were excluded if they
have previously proved VAP. Patients with weekly change of circuit were defined as
frequent change group. Demographic data were also collected. Poisson regression
models were used for person-day data analysis and testing confounding factors.
Results: During the study period, 848 person-days of weekly change group and 850
person-days of reference group were collected. The incidence was 5.9 cases per 1,000
patient-days in weekly change group and 3.8 cases per 1,000 patient-days in the
reference group. The hazard ration was 1.71 (95%CI, 0.41 ~ 7.12). Body weight and
age had no significant effect on the results. The pathogen of those VAP cases were
diverse including Pesudomonas aeruginosa, Acinetobacter baumannii, Klebsiella
pneumonia, Staphylococcus aureus, Staphylococcus aureus and Streptococcus
pneumaniae.
Conclusions: Routine weekly change of circuit seems having no significant effect on
preventing VAP in this analysis. However, the tubing should still be monitored closely.
If the tubing is contaminated with vomit, blood, or thick sputum, it should still be
replaced. Further larger scale prospective study should be performed to elucidate this
issue.
83
Echocardiography in the critical care setting—Experience and Expectation
彩色超音波心圖於重症單位臨床經驗分析
Chu-Chung Lin, Kai-Sheng Hsieh, Chi Chen1, Yong-Hwa Hsu1, Ta-Cheng Huang,
Ken-Pen Wong, Jia-Kan Chang2
Department of Pediatrics, Veterans General Hospital, Kaohsiung, Taiwan, Section of
Cardiology and Critical Care, Children’s Hospital1, Hu-Nan, China, Cheng-Hsin
General Hospital2, Taipei, Taiwan
林竹川、謝凱生、陳智 1、徐詠華 1、黃大誠、翁根本、張嘉侃 2
高雄榮民總醫院兒童醫學部；湖南兒童醫院心臟及重症科 1；台北振興醫院小兒
科2
Background: Echocardiography carries the advantages of non-invasiveness,
non-radiation, higher portability, relative cheapness compared to the high-tech
imaging, modalities and easy reproducibility. It is already widely applied in the
cardiology scheduled diagnosis laboratory such as echo-lab. However, its role in the
critical care setting has not been widely evaluated.
Methods: Between January 1, 2007 and December 31, 2008, we have prospectively
employed echocardiography in the pediatric and neonatal intensive care unit (ICU) for
the evaluation of pediatric and neonatal patients in the critical condition setting. The
echocardiographic examinations were performed using several commercially
available ultrasonographic systems. The echocardiographic examination protocol was
made according to the clinical situations of the patients. Basically, we employed the
integrated echocardiographic examination protocol. This protocol consists of
two-dimensional (2D), color flow mapping, pulsed/continuous wave Doppler
echocardiographic examination. Most of the images were stored in the video/digital
formats for latter reviewing.
Results: The ages of these patients ranged between premature neonates to 65 years
old. There were 228 patients received the echocardiographic examination in our
pediatric/neonatal ICU. The reasons for request of echocardiographic examination
were as following: to rule out or rule in congenital or acquired heart diseases: 78, to
evaluate cardiac functions: 73, to evaluate pericardial effusion: 31, to evaluate cardiac
valve competency: 15, to evaluate thrombosis in the cardiovascular system: 7 and
others in 15. The echocardiographic examinations were made in the post-cardiac
surgical patients in 9 patients.
Conclusions: Our study revealed that echocardiographic examination offers
important diagnostic information in the pediatric/neonatal critical care setting. It
allows rapid, and informative assessment for the critical evaluation of the
cardiovascular condition for patients in the pediatric/neonatal ICU. Our experience
would suggest that echocardiography should be performed quickly in suspecting
patients with cardiac disease or cardiovascular dysfunction in pediatric/neonatal ICU.
84
Respiratory Failure Caused by Community Acquired Pneumonia in Children
兒童社區性肺炎引起之呼吸衰竭
Pei-Ju Ting, Ming-Chih Lin, Po-Yen Chen, Sheng-Ling Jan, Yun-Ching Fu
Department of Pediatrics, Taichung Veterans General Hospital
丁佩如、林明志、陳伯彥、詹聖霖、傅雲慶
台中榮民總醫院 兒童醫學部
Background: Community acquired pneumonia (CAP) may contribute to severe
illness and mortality in previous well children. However, CAP induced respiratory
failure has seldom been reported in Taiwan. We retrospectively reviewed cases of
CAP induced respiratory failure in a medical center located in central Taiwan.
Methods: From Dec 2007 Dec 2008, all cases admitted to the pediatric intensive care
unit due to pneumonia were collected. Patients with neurologic diseases, previous
admission history, or systemic diseases were excluded. Demographic data, etiology,
length of stay, complications, mode of mechanical ventilation and mortality rate were
collected. Categorical data were analyzed by Fisher’s exact test. Continuous variables
were analyzed by Mann-Whitney U test.
Results: Totally, 18 cases were enrolled for analysis. Patients aged from 5 months to
9 years old with median 34 months. Streptococcus pneumoniae (S. pneumoniae) was
the most common pathogen among those patients (39%). Hamophilus influenzae was
the second most common (22%). Most cases of empyema were caused by S.
pneumonia (RR 9.4, p<0.01). Patients infected by S. pneumoniae were more likely to
be intubated but without statistical significance(RR 2.67, p=0.14). Both of the two
mortality cases were caused by S. pneumonia. Cases of pneumococcal pneumonia had
longer hospital stay (median 22 days V.S. 9 days, p=0.04) and longer PICU stay
(median 8 days V.S. 5 days).
Conclusions: CAP induced by S. pneumoniae contributes to a significant portion of
disease burden to our preschool children. It should be considered when choosing
initial antibiotics for CAP. Whole population vaccination of preschool children should
be considered by our health administrations.
85
Extracorporeal Membrane Oxygenation Support Improves Survival of Patients
with Fulminant Enterovirus 71 Infection
體外心肺循環系統 (ECMO) 改善瀕臨死亡之腸病毒重症兒童的存活率
Chao-Jen Lin1,2, Meng-Luen Lee2, Chun-Eng Liu3, Chang-Hua Chen3, Han-Yao Chiu2,
Lon-Yen Tsao2
Division of Pediatric Infectious Diseases1, Department of Pediatrics2, Division of
Infectious Diseases, Department of Internal Medicin3, Changhua Christian Children’s
Hospital, Changhua, Taiwan
林昭仁 1,2、李孟倫 2、劉尊榮 3、陳昶華 3、邱漢堯 2、曹龍彥 2
彰化基督教兒童醫院小兒染感科 1、兒科部 2、;染感科 3
Background: In 2008, an epidemic of hand-foot-mouth disease and herpangina
(HFMD/HA) was caused by enterovirus 71(EV71) infection in Taiwan. From January
to December, the severe cases (64 and 373, respectively) and deaths (4 and14,
respecticvely) were reported from our hospital and the Center for Disease Control in
Taiwan. The largest and most severe EV71 epidemic to date occurred in Taiwan in
1998. At that time, a total of 129’106 cases of HFMD/HA were reported; severe
neurologic complications (83 and 405, respectively), and (15 and 78, respecticvely)
children died from our hospital and the rest of Taiwan. However, the underlying
factors of increasing morbidity and mortality in EV 71 infection in this area than other
part of Taiwan remain unknown. The difference between two outbreaks in our hospital
is an established extracorporeal membrane oxygenation (ECMO) protocol for
cardiopulmonary failure of fulminant enterovirus 71 infection patients.
Methods: The age of the patient from birth to 14 years admitted due to HFMD/HA
were reviewed. Severe enterovirus cases were defined as the presence of the
symptoms/signs of HFMD/HA plus the occurrence of one or more complications such
as aseptic meningitis, encephalitis, poliomyelitis-like syndrome, encephalomyelitis,
pulmonary edema/hemorrhage, or death. Seven patients with fulminant enterovirus 71
infection were supported with ECMO between January to December, 2008.
Results: The mean age of the HFMD/HA patients was 2.1 years (range 1.2 months to
11 years), and the male-to-female ratio was 1.34:1. Most (92%) of the severe cases of
HFMD/HA occurred in children ≦3 years of age, M-mode echocardiography
frequently assessed the ejection fraction of the left ventricle in the fulminant EV 71
Infection cases and 7 patients treated with extracorporeal membrance oxygenation due
to the ejection fraction less than 40%.
Conclusions: Almost two thirds of the patients with fulminant enterovirus 71
infection who were supported with extracorporeal circulation survived and recovered
completely. The complications associated with cannulation may be attributed to the
fact that the patients were in shock or in full cardiac arrest. Earlier institution of
ECMO may decrease the complication rates and improve the overall survival.
86
The Fever Management and Comprehension of Acetaminophen syrup Written
Medication Instruction among Caregivers with Febrile Children in Hualien
花蓮地區小兒照顧者的退燒處置及對小兒退燒藥書面說明的理解度探討
Mei-Chuan Chang, Yueh-Chih Chen{1}, Shu-Chuan Chang{2}, Chia-Hsiang Chu{3}
Department of Nursing, Tzu Chi College of Technology, Hualien, Taiwan Department
of Nursing, National Taiwan University, Taipei, Taiwan1 Nursing Department,
Tzu-Chi Medical Center, Hualien, Taiwan 2 Department of Pediatrics, Tzu-Chi
Medical Center, Hualien, Taiwan 3
張美娟、陳月枝{1}、章淑娟{2}、朱家祥{3}
慈濟技術學院護理系 台灣大學醫學院護理系 1 慈濟醫學中心護理部 2 慈濟醫學
中心小兒科 3
Background: Fever is one of the most common reasons for parents seeking medical
attention for their children. Many parents are under the impression that fever is
harmful and apply various methods lower children’s body temperature.
Administration of acetaminophen is the most frequent method of fever management.
How to administrate medication appropriately becomes an important safety concern
for children fever management.
Methods: A descriptive study was conducted to explore the fever managements
applied by caregivers when children got fevers and the comprehension of written
medication instructions of acetaminophen syrup. A total of 102 caregivers with febrile
children under six years old were included. A self-designed questionnaire was used to
interview subjects on three aspects: (1) the demographic data; (2) the fever
managements at home; (3) the comprehension about administration of acetaminophen
syrup. For the third aspect, we showed subjects two written medication instructions,
one was on the drug package insert and the other was on the medication envelope.
Then they answered some questions about medication regarding to the information of
the instructions.
Results: Results showed: (1) 79% of the subjects were mothers; approximately 40%
had not completed high school; most of them were 26-35 years old. (2) the fever
management applied most frequently at home was administrating syrups of antipyretic
(66%); the second was administrating rectal suppositories of antipyretic (60%).(3)
One-third of the subjects had more than one misunderstanding on instruction of
medication with timing, interval time of administration and medication dosage after
reading the both written medication instructions. Almost two-thirds of the subjects
misunderstood the side effects of acetaminophen. Subjects without a high school
degree were associated with less written medication instruction comprehension
(X2=21.0; p<0.001).
Conclusions: In conclusion, caregivers frequently apply antipyretic to lower
children’s body temperature. And the written medication instruction is a major source
of information for caregivers to administer drug safely. It is important for medical
professionals to provide clients a readable written medication instruction.
87
Pediatric communication skill in interns
實習醫學生在兒科溝通技巧的表現
Tsuen-Chiuan Tsai, Ya-Chin Tsai, Sheng-Ru Wang
Department of Pediatrics, Taipei Medical University WanFang Hospital
蔡淳娟、蔡亞秦、王聖儒
台北醫學大學 市立萬芳醫院 小兒科
Background: Communication skill has been considered an important component of
clinical skills, which can improve patient satisfaction and clinical outcomes.
Communication in Pediatrics involves three parties, i.e., child patient, families and
doctor, thus it is especially challenging. This study is to determine the communication
abilities in interns.
Methods: This study used an OSCE station dealing with anger and confusion. The
hypothesized case was about a mother of a four year old girl who had asthma and just
took a prescription of prednisolone. A standardized patient (SP) portaited the anger
mother who challenged candidates for the use of prednisolone. Each candidate was
rated by a teacher and a SP independently.The items on the rating sheet included the
establishment of rapport, understanding of patient’s perspective, organization,
information collection, empathy, explanation and making plans. Borderline method
was used for standard setting. The interns’ scores were reported and the comparison
was made between teacher and SP. Questionnaires were distributed to interns at the
end of the examination.
Results: There were 32 interns in total. The mean scores were similar between
teacher (69.9) and SP (67.6). The cut-off score for “pass” was 68. Twenty-one out of
32 interns were deemed unsatisfied. The most difficult items were the performance on:
understanding of patient’s perspective, empathy, and explanation. The majority of
interns were found in low confidence when dealing with an anger patient. However,
students expressed great appreciation on the “learning experience”.
Conclusions: The majority of interns were found unsatisfactorily in communication
with difficult patients in Pediatrics. Enrichment program with more effective teaching
methods should be provided.
88
Using a Healthcare Matrix to Improve Care Quality and Physician Competency
運用健康照護矩陣提昇醫療品質與醫師稱職能力
Hsiao-Chuan Lin1,2, Ching-Yuang Lin1,2, Cheng-Yeng Tsai3, Walter Chen1,2,3
Department of Pediatrics 1, China Medical University Hospital; School of Medicine 2,
China Medical University; Department of Pediatrics 3, Bei-gang Hospital
林曉娟 1,2、林清淵 1,2、蔡承諺 3、陳偉德 1,2,3
中國醫藥大學附設醫院兒科部 1、中國醫藥大學醫學系 2、北港附設醫院小兒科 3
Background: The Healthcare Matrix was developed to link the IOM Aims for
Quality Improvement and the ACGME Core Competencies for Physicians to form a
6x6 grid. The Matrix provides a new tool to evaluate care quality and clinical
education simultaneously. This study involved the preliminary result of the Healthcare
Matrix for mortality and morbidity conferences in a medical center.
Methods: The Healthcare Matrix was applied in mortality and morbidity conferences
in the department of pediatrics. The conference began with a traditional case
presentation and literature review. Later, the Healthcare Matrix, which had been filled
prior to the meeting, was then presented and analyzed by all participants. The
Healthcare Matrix contains thirty-six cells. The resident and faculty examined
patient’s disease course to identify whether each of the six quality aims had been
reached. At first we discuss the first row, labeled Patient Care. A “Yes” answer means
further discussion unnecessary, while “No” warrants filling in the remaining rows
vertically. Finally, what had been learnt from the analysis that might improve patient
care was noted and recorded.
Results: From December 2007 through November 2008, six Matrix-based
conferences were conducted. Our experience highlights interpersonal and
communication skills, professionalism and systems-based practice, which are usually
overlooked in traditional mortality and morbidity conferences. Complex cases are
more suitable for such a matrix; very complex ones may necessitate daily revision. By
the way, senior residents and fellows are more competent in presentations due to the
complexity of the course.
Conclusions: Traditional mortality and morbidity conferences focus on details of
medical knowledge, but the matrix provides a new method for evaluating and
improving patient care across all disciplines. We recommended that the Healthcare
Matrix should be implemented as an innovative method to link clinical education and
quality of healthcare.
89
Clinical Outcome and Risk Factors in Hepatitis B Virus Related Hepatitis in
Infancy after Universal Hepatitis B Vaccination
全面施打 B 型肝炎疫苗後嬰兒時期 B 型肝炎的臨床表現及危險因子
Yu-Ru Tseng, Huey-Ling Chen, Jia-Feng Wu, Yen-Hsuan Ni, Hong-Yu an Hsu,
Mei-Hwei Chang
國立台灣大學醫學院附設醫院小兒部
曾鈺茹、陳慧玲、吳嘉峰、倪衍玄、許宏遠、張美惠
Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
Background: Hepatitis B virus (HBV)-related fulminant hepatic failure remained the
commonest cause of hepatic failure in infancy after universal vaccination. This study
aimed to analyze the clinical outcome in infants with HBV-related hepatitis.
Methods: Clinical data and outcome of 20 infants (14 males and 6 females) of
HBV-related hepatitis in pediatric department of National Taiwan University Hospital
from 1986 to 2006 were analyzed.
Results: Among the 20 cases, 5 (25%) presented with acute hepatitis B infection; 9
(45%) manifested with fulminant hepatic failure and 6 (30%) became chronic
hepatitis B cases. All acute cases had hepatitis B surface antigen (HBsAg)
seroclearance, development of anti-HBs antibodies and long-term survival. Among
the 9 fulminant cases, 3 had long-term survival. All of the survivors had HBsAg
seroclearance and development of anti-HBs but 1 of the survivors developed HBsAg
reversion 4 month after initial presentation and became chronic hepatitis B infection.
The ages of presentation were significant younger in the acute/fulminant group than
the chronic group (0.3 + 0.2 year v.s. 0.8 + 0.2 year, p=0.001). The initial and peak
ALT levels were significantly higher in the acute/fulminant group than that in the
chronic group (1687 + 663 IU/L v.s. 712 + 443 IU/L, p=0.004). Three (3/14, 21.4%)
had positive hepatitis B e antigen (HBeAg) at enrollment in the acute/fulminant group
while all (6/6) had positive HBeAg in the chronic group (p=0.001). All the 27 mothers
were HBV carriers. Maternal HBeAg were all negative in the acute/fulminant group,
while maternal HBeAg were all positive in the chronic group (p<0.001). All the cases
received on-schedule vaccination. Two of the 5 acute hepatitis B subjects received
self-paid HBIG while none of the fulminant subjects received HBIG (p=0.04).
Conclusions: Infants manifesting as HBV-related hepatitis may run an acute,
fulminant, or chronic course. High incidence of fulminant hepatitis was found in
patients with negative initial HBeAg, negative maternal HBeAg and onset below 4
months of age.
90
Lamivudine Therapy in Childhood Chronic Hepatitis B Infection
Lamivudine 在兒童 B 肝之治療成效
Shou-Yen Chen, Yao-Jong Yang
Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan.
陳首硯、楊燿榮
國立成功大學醫學院附設醫院小兒部
Background: Lamivudine as a potent inhibitor of viral replication is the first choice
of treatment of chronic hepatitis B virus (HBV) in children. This study aimed to
investigate the effect of lamivudine treatment in children with chronic HBV infection.
Methods: During 2002-2008, children, aged 3-16 years, with chronic HBV infection
regularly followed at our clinics were studied. Those who had elevated alanine
aminotransferase (ALT) levels more than 6 months concomitantly with a positive HBe
antigen or HBV DNA > 1.0 × 10^5 copies/ml were enrolled. Children previously
treated with antiviral agents or interferon-α were excluded. Each patient was treated
with oral lamivudine (3 mg/kg/day, maximum, 100 mg/day) for 52 weeks. We serially
evaluated the virologic and biochemical responses and complications.
Results: A total of 6 children (M/F = 3/3) with a mean age 6.6 years (range 4-11 years)
were studied. Among the enrolled patients, 5 were HBeAg positive and 1 were
HBeAg negative but high titer of HBV DNA initially. All children got normalization
of ALT and 5 of 6 (83%) had HBeAg seroconversion at the end of treatment. The
average time of normalization of ALT and loss of e antigen was 28.2 weeks (10-52
weeks) and 28.5 weeks (10 ~ 52 weeks), respectively. Children with HBeAg
seroconversion at the end of treatment had sustained virologic and biochemical
responses at the 6th month after therapy. Besides, 2 (33%) children had loss of
HBsAg. No significant adverse effects were observed.
Conclusions: Children with chronic hepatitis B treated with lamivudine are
associated with a significantly higher rate of normalization of ALT and HBeAg
seroconversion.
91
Eosinophilic Gastroenteritis in Taiwanese Children
臺灣地區兒童的嗜酸性粒細胞腸胃炎
Fu-Mien Tien, Jia-Feng Wu, Yung-Ming Jeng1, Hong-Yuan Hsu, Yen-Hsuan Ni,
Mei-Hwei Chang, Huey-Ling Chen
Department of Pediatrics, Hospital and College of Medicine, National Taiwan
University Children''s Hospital; Department of Pathology, National Taiwan
Unerversity Hospital1, Taipei, Taiwan
田馥綿、吳嘉峰、鄭永銘 1、許宏遠、倪衍玄、張美惠、陳慧玲
國立台灣大學醫學院附設兒童醫院小兒部,病理部 1
Background: Eosinophilic gastroenteritis is a rare disease of unknown etiology in
children. This study aims to evaluate the clinical manifestations of eosinophilic
gastroenteritis in children and explore the outcome and prognosis of our patients.
Methods: Between 1997 and 2008, 12 patients (eight boys and four girls from 10
families), median age 7.5 (0.3-14) yr, were diagnosed as eosinophilic gastroenteritis in
the Department of Pediatrics, National Taiwan University Hospital. The diagnosis was
confirmed by the presence of gastrointestinal symptoms, peripheral eosinophilia and
histology-proved biopsy.
Results: Initial symptoms included abdominal pain (5/12, 42%), anemia (4/12, 33%),
hypoalbuminemia (2/12, 17%), recurrent vomiting (1/12, 8%) and bloody stool (1/12,
8%). Peripheral eosinophilia (>600 eosinophil/μL) was present in 7 patients (58%) at
the initial diagnosis of eosinophilic gastroenteritis. The median absolute eosinophil
count in serum is 1051 (167-15605). Four children had positive skin prick test.
Panendoscopic exam was performed in all patients except one received colonoscopy.
One patients proceeded intra-operative enteroscope due to small bowel bleeding.
Endoscopic exam revealed ulcer disease in four patients (4/12, 33%). The treatment
included steroid alone (1/12), montelukast alone (3/12), steroid+montelukast (6/12),
steroid+montelukast+ketotifen (2/12). Among the nine patients treated with steroid,
three of them (33%) had successfully tapered off steroid without symptoms recurred.
Three patients (33%) had relapses after discontinuing steroid (6 episodes), two (22%)
still required low dose steroid and one patient (11%) lost follow-up. There was no
relapse in those three patients treated with montelukast alone.
Conclusions: Eosinophilic gastroenteritis is a rare disease in children. High index of
suspicion is required if peripheral eosinophilia and gastrointestinal symptoms exist.
Endoscopic biopsy with multiple sites is necessary if eosinophilic gastroenteritis is
suspected. Steroid is the main therapy but montelukast is also an alternative choice in
young children.
92
Anorectal Malformations: 20-year Experience in Mackay Memorial Hospital
直腸肛門畸型-馬偕醫院之二十年經驗
Ching-Fang Huang1,3, Hung-Chang Lee1, Chun-Yan Yeung1, Wai-Tao Chan1,
Chuen-Bin Jiang1, Jin-Cherng Sheu2, Nien-Lu Wang2
Department of Pediatrics(1), Department of Pediatric Surgery(2), Mackay Memorial
Hospital, Department of Pediatrics, Cardinal Tien Hospital (3)
黃靖芳 1,3、李宏昌 1、楊俊仁 1、陳偉燾 1、江椿彬 1、許錦城 2、王念陸 2
馬偕紀念醫院小兒科部(1), 小兒外科部(2),新店耕莘醫院小兒科部(3)
Background: Imperforate anus, which was also called anorectal malformation
(ARM), often combines with other anomalies and organ defects. Fecal incontinence is
reported as a major problem even though patients had received post sagittal
anorectoplasty procedure (PSARP).
Methods: In order to evaluate the associated anomalies, the postoperative sequelae
and long term complications, we reviewed 214 children of ARM from 1987 to 2007 in
Mackay Memorial Hospital. We also took down stool consistency under constipation
severity score (CSS), which was modified from Cleveland Constipation Score
(Agachan F et al. 1996) and symptom severity score(Alireza S. Keshtgar et al 2007),
Growth data were respectively analyzed, and compared with WHO 2006 growth
standard.
Results: Between 1987 and 2007, 214 patients underwent PSARP for ARM. A total of
121 patients were high-level ARM. 141 patients found to have fistula. Perianal fistula
is the most common type(30.4%). Among 94 female patients with ARM, 9.6% had
cloacal anomaly. Others were associated with cardiac(34.1%), renal(27.1%),
genitourinary(15.9%), bone(9.8%), gastrointestinal(1.4%), tracheal and
esophageal(16%), hearing loss(4.2%), single umbilical(1.9%), chromosomal
anomaly(6.1%) and Hirschsprung’s disease(4.7%). To follow patients with
postoperative ARM by using CSS, the incidence of constipation in our study showed
71.8%. 41 patients overcame the issues with good results later. 13 patients suffered
from diarrhea in the first year after PSARP, but half of them had good outcome after
then with others became constipation. CSS was higher in high-type
ARM(p<0.05).There were no significant difference between ARM and normal
population in weight evaluation at the age of 6m/o, 1.3m/o, 2y/o, 3y/o, 5y/o and
10y/o.
Conclusions: Constipation, in contrast to stool incontinence, is the most common
postoperative sequela in our series. Body weight gain can be achieved to normal after
treatment. Pediatrician need to build up patient’s and their parents’ confidence to
achieve better quality of life and assess in catch-up growth.
93
Congenital Web of Gastrointestinal Tract: 20-year Experience at Mackay
Memorial Hospital
消化道先天性蹼: 馬偕醫院之二十年經驗
Hsin-Hong Lin1,3, Hung-Chang Lee1, Chun-Yan Yeung1, Wai-Tao Chen1, Chuen-Bin
Jiang1, Jin-Cherng Sheu2, Nein-Lu Wang2
Departments of Pediatrics｛1｝, Department of Pediatric surgery｛2｝, Mackay
Memorial Hospital, Taipei; Department of Pediatrics, Taipei Medical University
｛3｝,Taipei, Taiwan
林信宏 1,3、李宏昌 1、楊俊仁 1、陳偉燾 1、江椿彬 1、許錦城 2、王念陸 2
台北馬偕紀念醫院小兒科部｛1｝
、小兒外科｛2｝;台北醫學大學附設醫院小兒科
部｛3｝
Background: To classify and evaluate the spectrum of congenital web in
gastrointestinal tract, including clinical courses and related factors.
Methods: Retrospective chart review was performed in 34 cases with congenital web
at Mackay Memorial Hospital from 1989 to 2008. All of the related parameters were
collected and analyzed.
Results: Nine patients have gastric web (7 male and 2 female), 22 have duodenal web
(13 male and 9 female), and 3 have jejunal web (2 male and 1 female). The mean of
diagnostic time (the time interval between birth and diagnosis) is 51 days in duodenal
group, 916 days in gastric group and 230 days in jejunal group. There is only a
statistically significant difference between gastric and duodenal group (51 days vs.
916 days, p < 0.01). The major symptom is vomiting. Surgery is done in almost all
except one patient. The patient without operation has gastric web and diagnosed by
panendoscopy. There is only one mortality case in this study.
Conclusions: Radiographic study and ultrasonography have their limitation for
diagnosis. The use of diagnostic time for differential diagnosis makes anticipate.
Gastric web always must be considered and panendoscopy is necessary, especially for
the patients presented as gastritis or GER without anticipated outcome after treatment.
Early surgical intervention for all congenital webs is essential for diagnosis and
treatment. However, larger case number makes result more reliable, and further study
is necessary.
94
Intestinal Angiodysplasia: a Retrospective Study of 18 Cases at MacKay
Memorial Hospital
腸道血管分化不良-台北馬偕醫院 18 病例之回溯性研究
Feng-Ju Chuang2, Hung-Chang Lee1, Chun-Yan Yeung1, Wai-Tao Chen1, Chuen-Bin
Jiang1,3
Departments of Pediatrics1, Mackay Memorial Hospital, Taipei; Department of
Pediatrics2, Chia-Yi Christian Hospital; Mackay College of Medicine, Nursing and
Management3, Taipei, Taiwan
莊豐如 2、李宏昌 1、楊俊仁 1、陳偉燾 1、江椿彬 1,3
台北馬偕紀念醫院小兒科部 1 嘉義基督教醫院小兒科 2 馬偕醫護管理學院 3
Background: Angiodysplasia, also referred to as vascular ectasia, is recognized as an
important cause of lower gastrointestinal bleeding. The diagnostic modalities include
colonoscopy, selective visceral angiography , operative angiography and helical CT
angiography. Angiodysplasia can affect any segment of the gastrointestinal tract. The
condition usually occurs in older adults and the right hemicolon is the most commonly
affected sites.Unlike the adults group, there is little experience with pediatric
population. To our knowledge, this study is known as the largest series of pediatric
cases at present
Methods: From July 2004 to October 2008, patients presented at the Mac Kay
memorial hospital with gastrointestinal hemorrhage diagnosed with angiodysplasia by
helical CT angiography were evaluated.
Results: Eighteen patients(14boys, 4 girls) with mean age of 7.1 yeras (range
1m-17years) were diagnosed. The time clinical onset to diagnose of angiodysplasia is
ranged from 1 week to 11 years, most around one to two weeks . All patients except
one had anemia with average hemoglobin level 7g/dL. The most commonly involved
areas were right ascending colon and terminal ileum. Four patients received surgery
treatment with resection of affected segments, the others were managed
nonoperatively. One patient was found to have Meckel diverticulum incidentally by
surgery.
Conclusions: In 1995, Torre Mongragon, L. et al. reported left hemicolon is most
frequently involved area in children . In our study, the most commonly involved areas
were right ascending colon and terminal ileum. Males are more than females. In
pediatric patients, angiodysplasia is a rare cause of gastrointestinal bleeding and
delayed diagnosis has been reported. This diagnosis should be considered when
patients had recurrent gastrointestinal bleeding.
95
Characteristics of Iron Deficiency and Iron Deficiency Anemia in Children
兒童鐵質缺乏與缺鐵性貧血的特徵
Shu-Ching Huang, Yao-Jong Yang
Departments of Pediatrics, National Cheng Kung University and Hospital, Tainan,
Taiwan
黃淑卿、楊燿榮
國立成功大學醫學院附設醫院小兒部
Background: Iron deficiency (ID) is one of the most common nutritional deficiencies
worldwide and is the leading cause of anemia, especially in children. Iron deficiency
anemia (IDA) impairs cognitive development and can increase susceptibility to
infectious diseases. This study aimed to evaluate the causative agents of childhood ID
and IDA and to investigate the treatment outcomes.
Methods: Children aged less than 18 years diagnosed of ID and IDA were included in
a retrospective study from 2001 to 2008. The ID was defined as the serum ferritin
level less than 12 ng/mL and the IDA as combination with hemoglobin less than 11.0
g/dL. The demographic data, identifying etiology, and treatment outcomes were
reviewed. The patients were categorized into three groups by age; Group 1: < 2 years,
Group 2: 2-10 years, Group 3a: > 10 years male, and Group 3b: > 10 years female.
Results: A total of 114 patients (Gr1: 43, Gr2: 13, Gr3a:18, and Gr3b: 40) were
enrolled. The median age of patients was 10.4 years (range 0.3-18 years) and the ratio
of male to female was 0.9. The mean values of hemoglobin, serum ferritin and
transferrin saturation were 8.3 g/dL, 4.6 ng/mL, and 6.3%, respectively. The most
common cause of ID or IDA was inadequate iron intake (35%) in Group 1, H. pylori
infection (23% and 28%) in Group 2 and Group 3a, and polymenorrhea (20%) in
pubertal females (Group 3b). Among the 69 patients with IDA, 65 of them had
hemoglobin improved after follow-up for a median of 6 months (range 3-27 months).
Conclusions: ID and IDA in children have variable etiology. The majority of patients
can become improvement after accurately identifying the causative factors and
prompt therapy.
96
Molecular detecting for Salmonella Enterocolitis with real-time PCR method
以即時聚合連鎖反應(Real-time PCR) 之方法檢測沙門氏菌腸炎
Min-Hsuan Hung1,3, Lung-Huang Lin1, Yu-Ti Fang2, Qing-Dong Ling2
Department of Pediatrics, Cathay General Hospital, Taipei, Taiwan1; Cell Biology Lab,
Cathay Medical Research Institute,Cathay General Hospital,Taipei,Taiwan2;
Department of Pediatrics, SongShan Armed Forces General Hospital, Taipei, Taiwan3
洪敏軒 1,3、林隆煌 1、方語緹 2、凌慶東 2
國泰綜合醫院小兒科 1、國泰綜合醫院臨床醫學研究中心 2、國軍松山總醫院小
兒科 3
Background: Salmonellosis is responsible for large numbers of infections in both
humans and animals. Conventional methods of isolation of Salmonella strains must
take 3–5 days. Besides, very small numbers of viable organisms present in the faeces
may fail to grow in artificial laboratory media. In the clinic, developing an accurate,
rapid and cost-effective diagnosis method is expected by the clinician and the
laboratory for appropriating antimicrobial treatment of Salmonella.
Methods: We collected the patients admitted to the Cathay General Hospital who had
diarrhea with blood tinged stool and/or mucus noted from Sep. 2007 to Dec. 2008. We
used a molecular detecting method that has been developed recently to examine in the
specimens from these patients by rectal swabs. Experimental processing including
brief culture and molecular detection for Salmonella enterocolitis using Real-time
polymerase chain reaction (qPCR) were performed immediately after clinical swab
sampling. The qPCR and streaking on plates were applied following pre-enriched the
samples by cultued in TSB broth for 0 to 3 hours.The sequences for the
Salmonella-specific oligonucleotide primers (ttr-6 and ttr-4) and the Salmonella target
probe (ttr-5) were designed based on a multiple alignment of the ttrBCA sequences.
Results: There were 45 patients specimens collected. The positive culture(stool or
swab cultures) numbers:17 ; The positive real-time PCR numbers:18. Only one case
culture was negative but PCR revealed positve. The PCR were all positive either stool
cultures or swab cultures revealed positive. The sensitivity is 100% and the specificity
is 96.5%.
Conclusions: Our results indicate that molecular detecting by real-time PCR seems to
be a more rapid, sensitive and cost-effective method compared to conventional stool
culture on the diagnosis of salmonella enterocolitis.
97
Lower Neutrophil Value in Omental Infarction Than in Acute Appendicitis in
Children
兒童網膜栓塞比急性闌尾炎的嗜中性白血球數值明顯較低
Ying-Hsien Huang1, Ya-Ling Yang2, Mao-Meng Tiao1, Kuo-Shu Tang1, Fu-Chen
Huang1, Shin-Ye Lee3
Department of Pediatrics 1 and Department of Anesthesiology2, Department of
Surgery 3Chang Gung Memorial Hospital - Kaohsiung Medical Center
黃瀛賢 1、楊雅玲 2、刁茂盟 1、唐國書 1、黃福辰 1、李信儀 3
小兒內科 1,麻醉科系 2，外科 3 長庚紀念醫院高雄醫學中心
Background: Omental infarction is a rare occurrence in the children. It often needs
not to receive operation but presents as an acute abdomen mimicking as acute
appendicitis. This study was conducted to investigate whether clinical and laboratory
data were distinguished between omental infarction and acute appendicitis.
Methods: A 1:4 case-control study of 7 patients with surgically and pathologically
proven omental infarction and age-matched and sex-matched 28 acute appendicitis
subjects was done. The clinical characteristics, image study and laboratory data were
analyzed.
Results: At presentation, all the 35 patients had right lower quadrant abdominal pain.
The frequency of nausea and fever were significantly lower in omental infarction
group than in acute appendicitis group (p<0.001 and p=0.018 respectively). The white
cell counts, CRP and neutrophil percentage were all demonstrated lower in omental
infarction group than in acute appendicitis group (p=0.001, p<0.001, and p=0.008
respectively). By using neutrophil percentage below 76%, we could separate omental
infarction from acute appendicitis (sensitivity 100%, specificity 100%).
Conclusions: A right lower quadrant abdominal pain patient with less than 76%
neutrophil percentage especial without nausea and fever, omental infarction should be
a considered diagnosis not acute appendicitis.
98
A proteomic approach to mitochondrial damage during cholestasis
膽汁鬱積性肝損傷粒線體蛋白質體學研究
Mao-Meng Tiao, Tsu-Kung Lin1, Cha-Wei Liou1, Chang-Chun Hsia2, Jiin-Haur
Chuang3
Departments of Pediatrics, Neurology1, Pediatric Surgery3, Chang Gung Memorial
Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine2,
Taiwan
刁茂盟、林祖功 1、劉家為 1、蕭長春 2、莊錦豪 3
高雄長庚小兒科,神經科 1,小兒外科 3,長庚大學 2
Background: Hepatic injury caused by cholestasis may be related to mitochondrial
dysfunction and oxidative stress. The purpose of this study was to investigate the
potential mitochondrial biomarkers for liver damage in cholestasis.
Methods: A rat model of biliary cholestasis was established without (sham) or with
bile duct ligation (BDL). Liver samples were obtained at 3 h post-bile duct ligation,
mitochondria were isolated and mitochondrial proteins were extracted and
quantitatively compared using two-dimensional gel electrophoresis. Differentially
expressed proteins (> 1.5-fold change relative to sham controls) were identified using
mass spectrometry.
Results: Over 200 protein spots were clearly identified from mitochondria isolated
from the liver cells in both groups. Preliminary spectrometric analyses demonstrated
significantly increased expression of HSP60 and decreased peroxiredoxin 6 in the
BDL rat liver mitochondria compared to that in sham-operated rats.
Conclusions: Our preliminary observation revealed significant changes in some
hepatic mitochondrial proteins between the sham and the BDL rats, indicating
involvement of mitochondrial biogenesis and dysfunction in response to cholestatic
liver injury.
99
Natural Course of Islet Cell Autoantibodies in Children with Type 1 Diabetes
Mellitus
第一型糖尿病病童胰島自體免疫抗體之自然病程
Yi-Ching Tung, Cheng-Ting Lee, Wen-Yu Tsai
Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
童怡靖、李正婷、蔡文友
台灣大學附設醫院小兒部
Background: To elucidate the natural course of islet cell autoantibodies in children
with type 1 diabetes after diagnosis.
Methods: Sixty-six newly diagnosed type 1 diabetic patients have been prospectively
followed up for islet cell autoantibodies once every three months for two years.
Results: At diagnosis, 42 patients (64%) were positive for glutamic acid
decarboxylase 65 autoantibodies (GADA) and 51 (77%) were positive for insulin
antigen 2 autoantibodies (IA-2A). Sixty-one of them (92%) had at least one of these
autoantibodies detected. The initial b-cell reserve is positively correlated with onset of
age and negatively correlated with the presence of GADA. After two years’ followup,
35 of 42 patients (83%) were still positive for GADA and 43 of 51 patients (84%)
were positive for IA-2A. Fifty-one of 61 patients (84%) still had at least one
autoantibody detected. The titers of these islet cell autoantibodies declined gradually
in most of these patients but some had fluctuation in islet cell autoantibody titers
during followup.
Conclusions: Although both GADA and IA-2A titers declined in most children with
type 1 diabetes, 84% of them still had islet cell autoantibodies detected two years after
diagnosis. Therefore, the determination of islet cell autoantibodies is still of value for
the classification of diabetes mellitus within two years after diagnosis.
100
The Relationships among Parent-adolescent Conflict, Diabetes Management,
Metabolic Control, and Depressive Symptoms in Adolescents with T1DM
第一型糖尿病青少年患者之親子衝突、疾病管理行為、疾病控制與憂鬱之關聯性
探討
Tian-Wen Feng1, Fu-Sung Lo, Chun-Yu Huang1
Division of Pediatric Endocrinology, Chang Gung Children’s Medical Center,
Taoyuan; Department of Psychology, Chung Yuan Christian University1, Chung Li
馮天妏*、羅福松、黃君瑜 1
林口長庚兒童醫學中心兒童內分泌科、中原大學心理學系 1
Background: 許多證據顯示，青春期為第一型糖尿病患者疾病控制由好轉壞的關
鍵時期，影響疾病控制的因素除了青春期獨特的生理特性外，疾病管理行為的執
行度、親子互動或心理適應因素亦有其影響力。其中有些研究曾探討親子衝突對
疾病控制的影響，但結果並不一致，因此目前仍難以確定親子衝突對於疾病控制
之影響機制。因此本研究旨在探討罹患第一型糖尿病之青少年，其青春期之不同
階段，親子衝突、疾病管理行為、疾病控制及憂鬱之間的關聯，以期了解影響青
少年糖尿病患者適應的因素，作為未來協助他們的參考。
Methods: 本研究以北部某醫學中心 9~20 歲經診斷為 T1DM 之青少年患者為研
究對象，共計 218 名，其中包含男性 93 名、女性 115 名；研究工具為基本資料
表、中文版自我照護量表、親子衝突量表、中文版糖尿病家庭衝突量表與青少年
憂鬱量表；資料分析以相關分析、變異數分析與多元迴歸分析進行假設考驗。
Results: 本研究結果指出 T1DM 青少年與父母之間的親子衝突 (一般衝突及糖
尿病特定衝突)與憂鬱呈正相關，亦即親子衝突愈高，T1DM 青少年愈憂鬱。T1DM
青少年與父母之間的糖尿病特定衝突程度，在青春期早期明顯高於青春期晚期。
T1DM 青少年之糖化血色素值，在青春期晚期時，明顯高於青春期早期，代表青
春期晚期時，疾病控制得較青春期早期差。疾病管理行為是親子衝突(一般衝突
與特定衝突因素一)之中介變項，如圖 1 所示，亦即親子衝突會先透過疾病管理
行為，間接影響糖化血色素之控制。雖然親子衝突(一般衝突及特定衝突)及疾病
管理行為分別與疾病控制(HbA1c)及憂鬱有顯著相關，但僅有疾病管理行為可顯
著預測疾病控制(HbA1c)，如表 1 所示；而親子衝突(一般衝突及特定衝突)與疾
病管理行為皆可顯著預測 T1DM 青少年之憂鬱程度，如表 2 所示。
Conclusions: 臨床工作人員與父母在面臨 T1DM 青少年之疾病適應上，可針對
其疾病管理行為與親子衝突的部分投入更多心力，以藉此改善 T1DM 青少年的
疾病控制與憂鬱狀況。
一般衝突
疾病
管理行為
糖化
血色素
特定衝突因素一
圖 1 親子衝突、疾病管理行為與糖化血色素之中介效果路徑分析圖
表 1 青春期階段、特定衝突、一般衝突、疾病管理行為與疾病控制之迴歸分析
效標變項 預測變項 原始係數
糖化
血色素
疾病
管理行為
-.112
β
Adjusted R2
R2 change
顯著性
-.452
.200
.204
p<.001
表 2 青春期階段、特定衝突、一般衝突、疾病管理行為與憂鬱之迴歸分析
效標變項 預測變項 原始係數
憂
β
Adjusted R2
R2 change
鬱 一般衝突
.121
.385
.251
.255
疾病
管理行為
-.238
-.347
.362
.113
特定衝突
.092
.117
.371
.012
顯著性
p<.00
1
p<.00
1
p<.0
5
101
The HLA-B Gene and Graves Disease in Children
HLA-B 基因和 兒童期 Graves 氏病
Yann-Jinn Lee1,2,3, Wei-Hsin Ting1,4, Fu-Sung Lo5, Chi-Yu Huang1,4, Chao-Hsu Lin6,
Hsin-Jung Li7, Chia-Jung Chan8, Chen-Mei Hung9, Ching-Cheng Tsang10, Shao-Yin
Chu11
Departments of 1Pediatrics and 2Medical Research, Mackay Memorial Hospital;
3
Department of Pediatrics, Taipei Medical University; 4Mackay Medicine, Nursing
and Management College; 5Department of Pediatrics, Chang Gung Memorial Hospital,
Taoyuan; 6Department of Pediatrics, Mackay Memorial Hospital, Hsin-Tsu;
7
Department of Pediatrics, St. Martin De Porres Hospital, Chiayi; 8Department of
Pediatrics, Tungs'' Taichung MetroHarbor Hospital, Taichung; 9Department of
Pediatrics, Cathay General Hospital, Hsin-Tsu; 10Taipei Municipal Chong-Sing
Hospital, Taipei; 11Department of Pediatrics, Buddhist Tzu-Chi General Hospital,
Hualien
李燕晉 1,2,3、丁瑋信 1,4、羅福松 5、黃琪鈺 1,4、林昭旭 6、李欣蓉 7、詹佳蓉 8、洪
禎鎂 9、曾慶昌 10、朱紹盈 11
台北馬偕紀念醫院 1 小兒科部 2 醫學研究部；台北醫學大學 3 小兒科；4 馬偕醫
護管理專科學校；林口長庚紀念醫院 5 小兒科部 桃園；新竹馬偕紀念醫院 6 小
兒科；聖馬爾定醫院 7 小兒科 嘉義；童綜合醫院 8 小兒科 沙鹿；新竹國泰綜合
醫院 9 小兒科；台北市立醫院中興院區 10 小兒科；佛教慈濟綜合醫院 11 小兒科
花蓮
Background: Graves disease (GD) is among the most prevalent autoimmune
endocrinological diseases in children and adolescents. The risk to a female sib of a
proband with GD is 10-15. The concordance rate is 20%-35% in monozygotic twins
but only 3%-7% in dizygotic twins. Therefore genetic factors play a role in its
pathogenesis. The HLA complex have been found to be associated with GD. However,
there are wide discrepancies reported among different ethnic groups. Therefore we
evaluated the association between the HLA-B gene and GD in children to clarify the
discrepancies.
Methods: The patients were 193 unrelated children with GD. Their age at the
diagnosis of GD was 10.2 ± 3.4 years (range 2.7 – 20.2 years). GD was diagnosed on
the basis of clinical and laboratory evidence (clinical symptoms and signs of
thyrotoxicosis, elevated free T4/total T4 and suppressed TSH levels, diffuse goiter,
with or without ophthalmopathy, and the presence of autoantibodies to thyroglobulin,
microsomes or both and TSH receptor antibody). The controls were 146 subjects
which included hospital personnel and individuals who underwent routine health
examinations or minor surgery. None had a history of autoimmune disease. All
patients and controls were Taiwanese. The HLA B alleles were typed using the Dynal
RELI SSO HLA-B typing kit (DYNAL, Invitrogen, Wirral, U.K.). The difference of
the distribution of the alleles of HLA-B between the patients and controls were
rrection for multiple comparisons.
Two-tailed Pc values of less than 0.05 were considered statistically significant.
Results: The frequency of HLA-B*4601 was higher in patients (152/386, 39.4%)
compared with that in controls (38/292, 13.0%) and the allele conferred a risk of GD
(OR = 4.34, 95%CI 2.92-6.46) (Pc = 7.15E-13).
Conclusions: The HLA-B gene is associated with GD in children and the
HLA-B*4601 confers a risk of GD.
102
Therapy of Dabetic Ketoacidosis in Children
兒童期糖尿病酮酸症的治療
Wen-Ling Guo1, Wei-Hsin Ting1,3, Chi-Yu Huang1,3, Chun-Chih Peng1, Yann-Jinn
Lee1,2,4
Departments of 1Pediatrics and 2Medical Research, Mackay Memorial Hospital;
3
Mackay Medicine, Nursing and Management College; 4Department of Pediatrics,
Taipei Medical University
郭紋伶 1、丁瑋信 1,3、黃琪鈺 1,3、彭純芝 1、李燕晉 1,2,4
台北馬偕紀念醫院 1 小兒科部 2 醫學研究部；3 馬偕醫護管理專科學校；台北醫
學大學 4 小兒科
Background: Diabetic ketoacidosis is an aute life-threatening complication of
diabetes mellitus. It may be present at onset of diabetes or occur in a patient with
preciously established diabetes secondary to relative insulin deficiency. An important
principle in the treatment of patients with DKA is careful monitoring of fluids,
electrolytes, fluid and insulin replacement and control of serum glucose as a priority.
The purpose of this study was to assess the efficacy of our DKA protocol prescribed
since January, 2002.
Methods: We treated 77 episodes of DKA in children according to the protocol:
Normal saline 10-20 ml/kg/hr till the blood pressure was normalized. Regular insulin
at 0.1 U/kg/hr in normal saline start at 2nd hr. Intravenous fluid (Na content
depending on the corrected Na level) at 1.5 times of maintenance rate. Adjusting
glucose concentration in the intravenous fluid to keep glucose level between 100 and
200 mg/dL. KCl and K Phosphate in intravenous fluid when plasma K level &#8804;
6.0 mmol/L and urine output observed. NaHCO3 infusion when pH was <7.0. DKA
was defined as a blood pH level of <7.30, a plasma glucose level of >13 mmol/l (250
mg/dl), a serum bicarbonate level of <15 mEq/l, and a positive serum acetoacetate test.
Statistical analysis: Continuous data was expressed as mean ± SD.
Results: The initial pH was 7.14(6.87-7.34), pCO2 was 21.6 mmHg(5.1-49.9),
HCO3- was 7.6 mEq/l (1.3-15), glucose was 584 mg/dl(312-1727), K was 4.8
mmol/L(2.8-7.3), Na was 135.4 mmol/L (121-152), BUN was 18.6 mg/dl(5.0-54.0),
Cr was 1.2 mg/dl(0.5-2.8) and P was 5.0 mg/dl (2.0-9.9). After treatment, glucose
level gradually normalized at 8.2 ± 7.9 (0.5-38) hours and HCO3 at 13.0 ± 7.6
(2.1-45.0) hours. All the patients successful recovered.
Conclusions: The protocol was effective and safe in treating DKA in children.
103
A SECOND CUT-OFF FOR SCREENING FEMALE NEWBORNS WITH
G6PD DEFICIENCY
女嬰篩檢 G6PD DEFICIENCY 需使用不同的界限值
JJ Liou, HY Chang, YH Chien, WL Hwu, NC Lee
Department of Pediatrics and Medical Genetics, National Taiwan University Hospital,
Taipei, Taiwan
劉蓁珍、張幸宇、簡穎秀、胡務亮、李妮鍾
台大醫院基因醫學部
Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the
commonest enzymopathy affecting red cell metabolism. Patients with G6PD
deficiency are predisposed to a number of diseases, including drug- or food-induced
acute hemolytic anemia, severe chronic nonspherocytic hemolytic anemia, and
neonatal jaundice. In Taiwan, newborn screening for G6PD deficiency started in 1986
to detect the affected babies and to give their parents instructions to prevent hemolysis.
G6PD deficiency is an X-linked disease, and all affected males and a portion of
female carriers both present low G6PD activities. However, the current cut-off,
designed for detecting affected males, is not effectve to screen female carriers because
of their high residual G6PD activity.
Methods: Screening for G6PD deficiency was performed on dry blood spots using
Neonatal G6PD set (PerkinElmer, USA) at the Newborn Screening Center. Newborns
with G6PD activities lower than the cut-offs were asked for a quantitative tests at
eighteen referral hospitals throughout Taiwan. The previous cut-off was 2.9 U/g Hb.
Results: G6PD activities were first obtained from 28,102 male and 25,415 female
newborns. The majority of data fit in normal distributions with a mean G6PD activity
of 5.269 U/g Hb (SD=1.03; range 0~13.8) for the total population; 5.209 U/g Hb
(SD=1.13) for males; and 5.336 U/g Hb (SD=0.9169) for females (the difference
between males and females reached statistic significance, p<0.001). In males, the
distribution chart revealed also a minor peak at 0.4 U/g Hb, which represented G6PD
deficiency. In females, this peak of G6PD deficiency was not present, but the
distribution curve tailed leftward with a visible peak on its left shoulder at 2.9 U/g Hb,
which might represent clustering of partial deficiency. Accordingly, we elevated the
cut-off for females to 3.3 U/g Hb. After testing for 23,070 newborns, we detected 120
females with blood spot G6PD activities between 2.9 and 3.3 U/g Hb. Among them,
74 (61.34％) were confirmed as affected. So we continued to test another 53,529
cases. Finally 583 in 637 males and 287 in 380 females were confirmed as affected.
The detection rate in male was 91%, and the positive prediction rate (PPR) was 92%.
After adjusting the cut-off for females, the detection rate raised from 48% to 75%,
though PPR decreased from 83% to 75%.
Conclusions: The incidences of G6PD deficiency were 1:48 in males and 1:89 in
females. A separate cut-off is necessary to detect females with partial deficiency. The
detection of females is important. Early detection would prevent hemolysis in those
babies, and also prevent confusions in genetic counseling.
104
Clinical Features of Taiwanese Patients with Osteogenesis Imperfecta
臺灣成骨不全症患者的臨床表現
Hsiang-Yu Lin1,2,3,4, Shuan-Pei Lin1,2,3,5, Chih-Kuang Chuang2,6, Ming-Ren Chen1,3,
Chia-Ying Chang1, Dau-Ming Niu4,7
Departments of 1Pediatrics and 2Medical Research, Mackay Memorial Hospital,
Taipei, Taiwan 3Mackay Medicine, Nursing and Management College, Taipei, Taiwan
4
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
5
Department of Infant and Child Care, National Taipei College of Nursing, Taipei,
Taiwan 6Medical College, Fu-Jen Catholic University, Taipei, Taiwan 7Department of
Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan
林翔宇 1,2,3,4、林炫沛 1,2,3,5、莊志光 2,6、陳銘仁 1,3、張家穎 1、牛道明 4,7
馬偕紀念醫院小兒科部 1, 醫學研究部 2; 馬偕醫護管理專科學校 3; 國立陽明大
學臨床醫學研究所 4; 國立台北護理學院嬰幼兒保育系 5; 天主教輔仁大學醫學院
6
; 台北榮民總醫院小兒科部 7
Background: Osteogenesis imperfecta (OI) (MIM# 166200, 166210, 259420, and
166220) is a congenital disorder characterized by increased bone fragility and low
bone mass. Despite its prevalence, information regarding the clinical features of this
genetic disorder is lacking in Taiwan. Thus, this study aimed at characterizing the
clinical features of OI patients in Taiwan so that a practical correlation could be
established for distinguishing different clinical subtypes of OI.
Methods: Review of medical records identified 48 patients with OI (33 females and
15 males; age range, 2 months to 53 years) during the study period from January 1996
through June 2008. Diagnosis and classification, using the classification system of
Sillence et al, were based on clinical and radiological characteristics. We also
analyzed the data of these patients among different subtypes, including clinical
presentations, physical examinations and bone mineral density findings.
Results: There were 33 females and 15 males with age ranging from 2 months to 53
years. Among these patients, 19 were classified as type I, 10 as type III, and 19 as type
IV. Height SDS were -0.76±0.91 in type I, -9.54±4.36 in type III, and -3.02±2.70 in
type IV. BMD SDS were -3.16±2.00 in type I, -5.35±2.13 in type III, and -4.19±1.77
in type IV. The clinical feature of blue sclera was present in 89% patients of type I,
80% of type III, and 58% of type IV. Eighty percent of type III patients had DI, in
contrast to 5% in type I and 42% in type IV. Annual fracture rate was 0.8±0.7 in type I,
4.4±0.6 in type III, and 2.0±0.7 in type IV. In type I patients, 84% had a family history
of OI, compared to 0% in type III, and 37% in type IV. Among three subtypes, there
existed statistically significant differences (p<0.05) in the following clinical features:
height SDS, weight SDS, BMD SDS, DI, bone deformity, scoliosis, walking ability,
annual fracture rate, and family history. However, no significant differences were
found in blue sclera (p=0.075) and hearing loss (p=0.832). In OI type I, the presence
of bone deformity was associated with the increment of age (r = 0.47, p<0.05). In OI
type IV, the presence of hearing loss was associated with the increment of age (r =
0.58, p<0.05). In addition, no other clinical features were associated with the
increment of age in OI types I, III and IV.
Conclusions: Nine of the 11 clinical features examined, including height SDS, weight
SDS, BMD SDS, dentinogenesis imperfecta, bone deformity, scoliosis, walking
ability, fracture rate, and family history, were significantly different among three types
of OI patients, which may be of help to evaluate patients and to establish their
prognosis.
105
LYSOSOMAL STORAGE DISEASES IN SOUTHEASTERN ASIA
東南亞地區溶小體儲積症概況
HY Yeh, YH Chien, WL Hwu, NC Lee
Department of Medical Genetics, National Taiwan University Hospital, Taipei,
Taiwan
葉慧英、簡穎秀、胡務亮、李妮鍾
臺大醫院基因醫學部
Background: Lysosomal storage diseases (LSDs) are caused by defects of one of the
several dozen lysosomal enzymes in the cells. The accumulation of the storage
materials in the lysosomal disturbs the function of the cells, and symptoms depend on
the types of cells that were affected. LSDs are identified in every ethnic group in the
world. After the launching of enzyme placement therapy for a number of the LSDs,
needs for laboratory diagnosis of LSDs are rapidly increasing. However,
epidemiological data for LSDs in many countries are still lacking.
Methods: The National Taiwan University Hospital (NTUH) serves laboratory
diagnosis of LSDs for Taiwan since early 1990s and for other Southeastern countries
since 2001. Currently, tests available are mucopolysaccharidosis type I, II, IIIA, IIIB,
IIIC, IIID, IVA ,IVB, VI, and VII, I-cell disease, Pompe disease, Fabry disease,
Gaucher disease, Niemann-Pick disease A/B, Gangliosidosis I and II, and Fucosidosis.
Results: Till the end of 2008, totally 371 cases from 11 countries were referred,
including 164 from India, 49 from Hong Kong, 38 from Malaysia, 32 from the
Philippines, and 31 from Thailand. The final diagnoses were mucopolysaccharidosis I
in 18 cases (10%), II in 29 (16%), III-B in 8 (4%), IV-A in 26 (14%), VI in 11 (6%), I
cell disease in 15 (8%), Gaucher disease 22 (12%), Fabry disease 9 (5%), Pompe
disease 23 (13%), Niemann-Pick disease A/B 7(4%), and others 14 (8%). Thirty-three
cases revealed normal LSD enzyme activities.
Conclusions: Almost all kinds of LSDs could be found in the Southeastern countries.
The distributions of diseases are also unique in this area, and also between countries.
The availability of a central referral laboratory is very helpful in making diagnosis of
rare diseases. Through this service, knowledge about the prevalence of LSDs in this
area will be approached and strategies, including treatment and genetic counseling,
can be designed.
106
Clinical Findings, Cytogenetic Study and Genetic Counseling of Supernumerary
Marker Chromosomes
額外標誌染色體的臨床表徵細胞染色體分析與遺傳諮詢
Li-Min Chen,, Hui-Pin Hsiao3, Mei-Chyn Chao, Yuli Chang1, Yi-Hui Huang1,
A-Hsiang Chen1, Ya-Wei Huang1, Yi-Ping Wu1, Mei-Lang Huang1, Cheng-Chu Wang2
Division of Genetics, Endocrinology and Metabolism, Department of Pediatrics,
Cytogenetics Lab, Department of Clinical Laboratory1, Genetic Counseling Center2,
Kaohsiung Medical University Hospital, Department of Pediatrics, Kaohsiung
Municipal Hsiao Kang Hospital, Kaohsiung, Taiwan
陳利旻、蕭惠彬 3、趙美琴、張由俐 1、黃意惠 1、陳阿香 1、黃雅薇 1、吳依萍 1、
黃美蘭 1、王禎鞠 2
高雄醫學大學附設中和紀念醫院 小兒科部遺傳及內分泌新陳代謝科、檢驗醫學
部 細胞遺傳室 1、遺傳諮詢中心 2、 高雄市立小港醫院小兒科 3
Background: Supernumerary marker chromosomes (SMCs) are defined as
structurally abnormal chromosomes that cannot be identified by conventional banding
cytogenetics alone. They are found in about 0.043% of human population and 1 in
1000 prenatal diagnosis. SMCs are a heterogeneous group which are quite harmless
and associated with phenotypic normality. However, there have been estimated to
result in abnormal phenotype in 30% of SMC carriers. The causes of SMCs may be
familial, but the majority will prove to be de novo.
Methods: We reviewed 19 cases of SMCs since 2000, which were detected from
amniocentesis or peripheral blood lymphocytes with G-banding technique. Therefore,
there were confirmed by C-banding and NoR-banding analysis, further FISH or
spectral karyotype. Parental chromosome studies were suggested. Clinical features
and genetic counseling were also recorded.
Results: 57.9% of total 19 cases of SMCs were proven with chromosomes 13, 14 or
15, and 22, remaining 5 cases and 3 cases were chromosomes X and Y, respectively.
47.4% cases were mosaic SMCs and familial SMCs were about 21%. Five of total 9
cases prenatally diagnosed and asked for determination. Mosaic SMCs with X or Y
chromosomes showed Turner like syndrome and short stature. Other SMCs cases
involved chromosomes 14, or 15, or 22 whom had long term follow up with no
specific anomalies so far.
Conclusions: Supernumerary marker chromosomes are a diagnostic problem in
clinical cytogenetics because of the origin is usually unknown and difficultly to
identify. Thus, molecular cytogenetics, FISH and multicolor FISH or whole-genome
arrays for comprehensive analysis of SMCs may need for genetic counseling.
107
Combinatorial Analysis in Fetal Transcriptome of Down Syndrome for Gene
Prioritization, Mechanism Validation, and Drug Target Selection
在唐氏症胎兒的基因表現體，利用信息組合分析法推測關鍵基因的優先化，唐氏
症機制的確認和可能藥物的選擇
Cheng-Hsien Tsai1, Yi-Kuen Mao2, Ching-Yu Chou3, Yi-Shun Lin4, Fon-Jou Hsieh5,
D. Frank Hsu6
Department of Pediatrics, National Taiwan University Hospital Yunlin Branch1,
Department of Obstetrics and Gynecology, National Taiwan University Hospital
Yunlin Branch2, Departments of Obstetrics and Gynecology, Cathay General Hospital3,
Welgene Biotech. Co., Ltd., Teipai, Taiwan4, Departments of Obstetrics and
Gynecology, National Taiwan University Hospital5, Department of Computer and
Information Science, Fordham University6
蔡政憲 1、毛義坤 2、周靜玉 3、林怡杏 4、謝豐舟 5、許德標 6
台大醫院雲林分院小兒部 1, 台大醫院雲林分院婦產部 2, 國泰醫院婦產部 3, 威健
科技股份有限公司 4, 台大醫院婦產部 5, 美國紐約 Fordham 大學電腦與資訊科學
系 6,
Background: Down syndrome (DS) is a human disorder of trisomic human
chromosome 21 (HSA21) with genomic dosage imbalance. Two hypotheses: the
“gene dosage effect” and the “amplified developmental instability” were proposed but
not yet quantitatively combinatorial analysis. This study was to apply Combinatorial
Fusion Analysis (CFA), Gene Set Enrichment Analysis (GSEA), and Connectivity
Map (C-MAP) as tools for gene prioritization, validation of DS mechanism, and drug
target selection that might be translatable into treatment for DS
Methods: Primary cultures of the amniocytes were collected from the fetus between
16-22 weeks of pregnancy, following routine diagnostic cytogenetic analysis. Gene
expression data were obtained using hybridized Human 1A (version 2) oligo
microarray (Agilent Technologies, USA) with 21,073 probes representing
approximately 18,390 genes. The global transcriptome differences between DS and
euploidy state were analyzed by microarrays. First, we used GSEA as performance
function for gene sets prioritization in global transcriptome differences. Then six
microarray statistical tests were reviewed, including (1) two-sample t test, (2) Welch’s
test and (3) Significance Analysis of Microarrays (SAM) test (4) Wilcoxon rank sum
test, (5) coefficient of variation (CV), (6) F test of variance. Second, we applied CFA
as 63 combinations of any quantitatively combinatorial analysis from those 6
statistical tests. Third, we applied the optimal gene sets prioritization to query in
C-MAP to get candidate perturbagens in the form of agonists or antagonists. We
compared these perturbagens to known potential drug targets for DS.
Results: Amniocytes were collected from four fetuses of trisomy 21 (2 cases of 47,
XX +21 and 2 cases of 47, XY +21) and six euploidy (3 cases of 46, XX and 3 cases
of 46, XY). By GSEA analysis, the global transcriptome differences showed only 3
statistically gene sets among the whole genomic 386 gene sets, and all three gene sets
were located on the HSA21, especially highest enrichment score on gene set of
HSA21 Q22 (DS Critical Region). Combinatorial data fusion-based discretization by
union of top 1000 gene probes in either of 6 tests showed 2,223 genes up-regulated,
and 1,831 genes down-regulated among 18,390 genes investigated. Among 63
combinations, SAM test had highest enrichment score in 54 genes of HSA21 Q22.
The visualization of networks including p38 MAPK pathway, PRX-actin pathway,
and NFAT-calcineurin pathway were found. By C-MAP, we found 5 positive scoring
of perturbagens (LY-294002, valproic acid, α-estradiol, 17-allylamino-geldanamycin,
and trichostatin A) as agonists, and 4 negative scoring perturbagens
(tetraethylenepentamine, bucladesine, prazocin, oxaprozin) as antagonists. We found
similar findings to potential drug targets from in vivo studies.
Conclusions: The broad pathway analysis with CFA, GSEA, C-MAP combination
showed gene sets prioritization, mechanism validation and potential perturbagens for
treatment of DS.
108
HEMODIALYSIS IS A SAFE AND EFECTIVE METHOD TO REMOVE
TOXINS FOR NEWBORNS WITH INBORN ERRORS
在先天代謝異常患嬰使用血液透析是安全有效的方法
YH Chien1,2, WL Hwu1,2, IJ Tsai2, ET Wu2, SC Huang3, NC Lee1,2, UK Tsao3
Department of Medical Genetics1、 Pediatrics 2、and Surgery 3, National Taiwan
University Hospital, Taipei, Taiwan
簡穎秀 1,2、胡務亮 1,2、蔡宜蓉 2、吳恩婷 2、黃書健 3、李妮鍾 1,2、曹永魁 3
台大醫院基因醫學部 1、小兒部 2、外科部 3
Background: Detoxification is the most critical step in preventing death and
minimizing brain damages in inborn errors of metabolism, and hemodialysis (HD) has
the fastest clearance rate. However, difficult vascular access, hemodynamic instability,
and the lack of appropriate equipments have all been regarded as reasons preventing
the use of HD in small babies, so other ineffective modalities like hemofiltration and
peritoneal dialysis are still used.
Methods: From Dec. 2006 to Dec. 2008, we performed 10 sessions of HD for 6
patients with either urea cycle disorders (n=1), maple syrup urine disease (MSUD)
(n=3), or methylmalonic academia (n=2). Vascular assesses were done by a cardiac
surgeon, and the dialyses were performed with dialyzing filters and tubes specialized
for small babies. Blood samples were obtained immediately before and after the
procedures, and time for 50% reduction of the pre-dialysis toxin level (blood
ammonia for urea cycle disorders; plasma leucine for MSUD; and blood spot
methylmalonic acid [MMA] for methylmalonic acidemia) was calculated. The data
were compared to 10 sessions of other renal replacement therapy (RRT) for 8 patients
with either urea cycle disorders (n=3), maple syrup disease (n=1), or methylmalonic
acidemia (n=4).
Results: For patients who received HD, the procedures were done at ages from 3 days
to 7 years, with body weights from 3 kg to 20 kg (mean 3.5 kg). Highest toxin levels
recorded were 3,607 μM for leucine, 691 μM for ammonia, and 94.34 μM for MMA.
For patients received other RRT, the procedures were done at ages from 12 days to 7
years, with body weights from 2.3 kg to 20 kg (median 8.3 kg). Their highest toxin
levels recorded were 2,300 μM for leucine, 1,070 μM for ammonia, and 976.6 μM for
MMA. Time for 50% reduction of the toxin level was 2.15 hours to 4.1 hours (mean
2.93 hours) in the HD group; and was 8.16 hours to 36 hours (mean 15.59 hours) in
the non-HD group.
Conclusions: Hemodialysis is the most effective modality to remove ammonia,
leucine, or MMA. By clearing toxic metabolites rapidly, HD gives the best outcome to
young infants with inborn errors of metabolism.