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THE JOURNAL OF THE JAPAN PEDIATRIC SOCIETY
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Vol.117, No.4, April 2013
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Original Article
Title
Effects of Low-dose Budesonide Inhalation Suspension on Young Children with Mild-to-moderate Persistent Asthma
Author
Naoto Imamura1) Chiho Tatsumoto2) Yuichi Adachi3) Gyokei Murakami4) Tatsuya Fuchizawa5) Shigemi Yoshihara6) Motokazu Nakabayashi7) Akira Akasawa8) Youichi Onoue9) and Toshio Katsunuma10)
1)Imamura Hospital
2)Yano Family Clinic
3)University of Toyama
4)Murakami Pediatric and Allergy Clinic
5)Saiseikai Takaoka Hospital
6)Dokkyo University School of Medicine
7)Itoigawa Sogo Hospital
8)Tokyo Metropolitan Children's Medical Center
9)Onoue Pediatric Clinic
10)Jikei University School of Medicine, Daisan Hospital
Abstract
Introduction
The Japanese Pediatric Guidelines for the Treatment and Management of Asthma recommends the administration of budesonide inhalation suspension (BIS) for young children with mild-to-moderate persistent asthma. However, the results of a Japanese long-term BIS intervention study (0.5 to 1.0 mg/day) in asthmatic children between the ages of 6 months to 5 years suggested adrenocortical suppression.
Subjects and Method
This study (Mild One Study) was a multicenter, randomized, open-label, parallel-group study. After a 2- to 4-week observation period, patients with mild-to-moderate persistent asthma between the ages of 6 months and 5 years were randomly assigned to a BIS arm (inhalation of BIS at 0.25 mg once/day) or a cromoglycate inhalation solution (CIS) arm (inhalation of CIS at 20 mg 3 times/day). Treatment lasted for 12 weeks. The primary endpoints were daily activity interference score and nighttime sleep disturbance score.
Results
A total of 37 subjects were enrolled, and 33 were assigned to either the BIS arm or the CIS arm. The total interference/disturbance score in the BIS arm was significantly lower (0.10±0.21; p=0.005) after treatment than that in the observation period (0.98±1.16). However, no significant decreases were observed in the CIS arm. There were no significant differences in the changes in serum cortisol levels in both groups.
Discussion
The results suggest that BIS (0.25 mg/day) is as effective as, or more effective than, CIS (60 mg/day), and may be a useful form of treatment for young children with mild-moderate asthma.
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Original Article
Title
Adipose Tissue Distribution in Children and Adults with Prader-Willi Syndrome: Changes with Age and Effects of Growth Hormone Treatment
Author
Yoshiko Abe Yuriko Tanaka Yuji Oto Hisashi Itabashi Masahisa Shiraishi Nobuyuki Murakami and Toshiro Nagai
Department of Pediatrics, Dokkyo Medical University Koshigaya Hospital
Abstract
The Prader-Willi syndrome (PWS) is a genetic disorder associated with chromosome 15q11-13 and shows characteristic age-related clinical features, in particular, marked anthropometric changes. Emaciation is observed during infancy, and severe obesity is seen in older children and adults. Growth hormone (GH) treatment modifies the anthropometric natural history of PWS patients. In this study, we examined the changes in the body composition of 48 PWS patients aged 6 to 39 years, concentrating on the amount of abdominal visceral adipose tissue (VAT), the amount of subcutaneous adipose tissue (SAT), the VAT/SAT (V/S) ratio, and serum adiponectin levels.
In patients undergoing GH treatment, the amount of SAT increased markedly with age, but that of VAT remained low. In patients who discontinued GH treatment, the amount of VAT increased with age, as was the case for non-GH-treated patients. In the obese group (body mass index≥25 kg/m2; n=22), adipose tissue was predominantly distributed subcutaneously, with only 5 of the 22 patients showing a high V/S ratio (p>0.4). Serum adiponectin levels showed strong negative correlations with the amounts of both VAT (r=-0.54, p<0.001) and SAT (r=-0.50, p<0.001). Adiponectin levels were within the normal range, even in the obese group, except in the case of 2 patients. To maintain low VAT accumulation, GH treatment is desirable even in adult PWS patients.
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Original Article
Title
Risk Factors for Refractory Mycoplasma pneumoniae-induced Pneumonia That Required Intravenous Steroid Administration
Author
Yoshitaka Murakami Satoshi Honjo Kenji Okada Yohei Arakaki Yuko Amimoto Natsuko Masumoto Naohiko Taba Yoko Murakami Chikako Motomura Yoshihisa Nagatoshi and Hiroshi Odajima
Department of Pediatrics, Fukuoka National Hospital
Abstract
We retrospectively reviewed 142 cases with Mycoplasma pneumoniae-induced pneumonia hospitalized in the period from April 2010 to March 2011. We compared their clinical and laboratory findings with those of the 135 cases successfully treated with antibiotics and with those of the remaining 7 refractory cases with a prolonged fever. In these 7 refractory cases, the levels of the possible biomarkers for hypercytokinemia, serum ferritin and urinary beta-2 microglobulin were elevated, and defervescence was achieved after intravenous steroid administration. The 7 refractory cases with persistent fever shows significant differences from the 135 cases in terms of white blood cell count [geometric mean, 6,237/μl (95% confidence interval (5,901-6,593) vs. 4,505/μl (2,653-7,648)], AST [29 IU/L(28-31) vs. 76 IU/L(42-140)], ALT [16 IU/L(15-17) vs. 42 IU/L(22-82)], and LDH [278 IU/L(266-290) vs. 590 (386-900)](p≤0.01 for all). The odds ratios for the refractory pneumonia under AST≥67 IU/L, ALT≥85 IU/L, and LDH≥460 IU/L were 187.97 (9.76-3,620.05), 75.91 (4.37-1,319.61), and 364.75 (18.23-7,297.67), respectively, adjusted for age, sex, leukopenia, and serum CRP. Serum LDH could be easily measured compared with the cytokine markers and serum cytokines. Systemic steroid therapy may be indicated for refractory M. pneumoniae-induced pneumonia when LDH is elevated.
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Original Article
Title
Clinical Features of Simple Coarctation of Aorta
Author
Kenji Sugamoto Kiyoshi Ogawa Kenji Hoshino Takashi Hishitani Yukinori Saito and Takuma Mori
Department of Cardiology, Saitama Children's Medical Center
Abstract
Simple coarctation of the aorta (simple CoA) is relatively rare compared with the complex form. We investigated the clinical features of simple CoA retrospectively. From April 1983 to December 2011, we encountered 29 cases of simple CoA, including 2 patients with Turner syndrome. The distribution of age at diagnosis showed 2 peaks, namely, at early infancy and as schoolchildren. There were characteristic symptoms in each age-group. Serious cardiovascular collapse, such as in cases of shock or congestive heart failure, was very common in the neonatal and infantile group. On the other hand, serendipity detection of heart murmur and hypertension was common in the schoolchild group. Among the 29 patients, 10 had obstructive lesions in their left heart, 5 of whom had a bicuspid aortic valve. Some cases required emergency surgical operation, particularly among the neonatale cases. Although some postoperative problems remained, such as residual stenosis and hypertension, the postoperative prognosis of the patients increasingly became satisfactory. It is important to note that simple CoA has various symptoms and clinical courses depending on the patient's age.
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Original Article
Title
Onset of Complications and Management of Cockayne Syndrome Type I
Author
Eriko Nakajima1) Ayako Hattori1) Tetsuya Ito1) Satoru Kobayashi1) Yoko Nakajima1) Naoki Ando1) Katsuo Sugita2) and Shinji Saitoh1)
1)Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences
2)Department of Clinical Medicine, Faculty of Education, Chiba University
Abstract
Cockayne syndrome is a disorder in DNA repair. Its natural course, however, remains unclear. We retrospectively examined the clinical courses of 4 patients with Cockayne syndrome type I. By the age of 10 years, 2 of these patients had developed hypertension, 2 had hypercholesterolemia, and 3 had significantly high levels of serum creatinine after having experienced a gradual increase. Hyperuricemia was present in all the patients; serum uric acid levels, which had already reached significantly high levels before the age of 10 years, decreased with medication, but gradually increased again as serum creatinine levels increased. These cases showed that patients with Cockayne syndrome type I develop many complications by age 10. The early diagnosis and treatment of hypertension, hyperuricemia and hyperlipidemia is very difficult; therefore, routine medical examination should be conducted for these complications in patients of preschool age.
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Original Article
Title
Imported Inactivated Polio Vaccine Use in Kobe City
Author
Kazumichi Fujioka1)2) and Kazumoto Iijima3)
1)Department of Pediatrics, Kobe Kaisei Hospital
2)Department of Pediatrics, Kobe University Graduate School of Medicine
3)Division of Child Health and Development, Department of Pediatrics, Kobe University Graduate School of Medicine
Abstract
We have used imported inactivated polio vaccine (IPV) for many years, exclusively for international travelers. In February 2010, a case of vaccine-associated paralytic poliomyelitis (VAPP) was reported in Kobe city. This news was broadcast repeatedly, and caused widespread anxiety among citizens regarding the oral polio vaccine (OPV). Subsequently, the number of patients visiting our hospital to ask for IPV increased dramatically. In July 2010, we extended our application of IPV to routine vaccination. As of March 2011, we have given IPV vaccinations to 135 children (243 shots). This represents a significant increase, with more than half of the cases visiting from outside the city. Our IPV schedule consists of a series of 4 injections, including 3 doses of primary immunization given at 4-8 week intervals, followed by a booster dose at 4-6 years. We confirmed seroconversion in 31 subjects who completed primary immunization. There are many problems with the use of imported IPV in Japan, including lack of public awareness of issues with unapproved vaccines, absence of government compensation, scheduling differences among institutes, and the localities of hospitals providing IPV. The number of hospitals providing IPV and the number of patients seeking IPV will probably increase in the near future. Therefore, constructive discussion about universal provision of safer polio vaccinations for children in Japan is necessary.
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Original Article
Title
Two Cases of Methimazole-induced Polyarthritis with Graves' Disease in Children
Author
Masako Hayashi Hidetoshi Sato Yohei Ogawa Keisuke Nagasaki Toru Kikuchi Makoto Uchiyama and Akihiko Saitoh
Department of Pediatrics, Niigata University Medical and Dental Hospital
Abstract
Methimazole (MMI) is a common anti-thyroid drug (ATD) for Graves' disease (GD), although many side effects have been reported. Polyarthritis is known to be a severe side effect of ATDs; however, there are only a few reports in children. The clinical course and therapeutic strategy for polyarthritis are currently unknown. We report 2 cases of GD in children who developed polyarthritis following MMI treatment. GD was diagnosed in both patients, and they were initially given MMI (30 mg/day). In both patients, skin rashes occurred 2 weeks after MMI administration, and multi-arthralgia developed after several days. In the first patient (an 11-year-old girl), potassium iodide treatment was initiated after MMI cessation, and finally, a thyroidectomy was performed. In the second patient (a 13-year-old girl), the ATD was changed to propylthiouracil. Arthralgia improved 1 week after MMI cessation in both cases. It is possible that the multi-arthralgia induced during the ATD treatment is a severe side effect of arthritis syndrome. Therefore, it is necessary to differentiate between anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, pseudo systemic lupus erythematosus, and polyarthritis. A change in treatments should be considered after checking for purpura, rheumatic arthritis and auto-antibodies, including myeloperoxidase-specific-ANCA. Physicians should be aware of the manifestations of arthralgia as a side effect of ATDs.
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Original Article
Title
A Case of Septic Arthritis Caused by Serotype 23F Streptococcus pneumonia after Vaccination Three Times with 7-valent Pneumococcal Conjugate Vaccine
Author
Eriko Kudo Mikio Yoshioka Syuntaro Tsumagari Daisuke Sasaki Mitsuru Nawate Noriko Yanadume Takaaki Shikano and Yutaka Takahashi
Department of Pediatrics, KKR Sapporo Medical Center
Abstract
We report an 11-month-old girl with septic arthritis of the left hip joint. She was admitted to our hospital under a diagnosis of suspected septic arthritis. We performed articular dissection and drainage, and started her on antibiotics. She was discharged without sequelae. Streptococcus pneumonia was isolated from both drained fluid and blood culture. The isolated organism was identified as serotype 23F, which is a serotype included in the 7-valent pneumococcal conjugate vaccine (PCV7). We suspected primary vaccine failure because she had received PCV7 three times at 6, 8 and 9 months of age before admission. We determined immunoglobulin G (IgG) antibody levels and opsonic activity against 7 vaccine serotypes. The serum IgG level and opsonic activity specific for serotype 23F were significantly lower than those for the other serotypes included in PCV7, both on admission and 2 months after admission. Furthermore, opsonic activity against serotype 23F was not elevated even after the 4th PCV7 vaccination (5 months after admission). This serotype-specific hyporesponsiveness may reflect a pneumococcal carrier state before vaccination or immune paralysis due to a large pneumococcal polysaccharide antigen load.
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Original Article
Title
A Case of an Infant with Kawasaki Disease Developing Coronary Aneurysm in the Convalescent Period
Author
Ikuo Hashimoto Hiroyasu Nakagawa Hisashi Kaneda Youko Shitano and Masayoshi Miura
Department of Pediatrics, Toyama City Hospital
Abstract
A 6-month-old boy was admitted to our hospital on the 5th day of illness diagnosed as Kawasaki disease (KD), and he presented with 6 typical symptoms. Intravenous immunoglobulin therapy (2.0 g/kg) was started from the 5th day of illness. All symptoms improved immediately after the immunoglobulin therapy and the boy was discharged on the 11th day since onset. Echocardiographic examination revealed slight bilateral coronary dilatation (2.5 mm each). Echocardiography on his routine follow-up medical examination at our hospital on the 26th day of illness showed a coronary artery aneurysm of 3.8 mm diameter on the left main trunk. On the 31st day of illness, erythema of the oral mucosa reappeared and echocardiography revealed further progression in the size of the coronary aneurysm to 6.0 mm diameter. We repeated high-dose intravenous immunoglobulin therapy (2.0 g/kg), which immediately improved his oral mucosal erythema. On the 41st day of illness, the left coronary aneurysm regressed to about 3.6 mm in diameter. In patients with KD, particularly in infants, we need to pay careful attention to coronary artery involvement within at least 1 to 2 months after the onset of illness.
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Original Article
Title
Twins with Neonatal Alloimmune Thrombocytopenia
Author
Kenji Mine Shinichiro Sekiya Masato Hirabayashi Jun-ichi Nakashima Yuichi Kuroyanagi Shoji Tsuji Atsushi Ohashi Yukihiro Noda Takahide Nakano Hirohide Kawasaki Yo Kinoshita and Kazunari Kaneko
Department of Pediatrics, Kansai Medical University
Abstract
We report a rare case of neonatal alloimmune thrombocytopenia (NAIT) due to anti-human lekocyte antigen (HLA) antibodies diagnosed in 1-day-old twins born to a Japanese mother and a Thai father. They were born at 36 weeks of gestation by cesarean section because of cervix dilatation. At birth, petechiae were noted spreading over their body, and they were admitted at 1 day of age for evaluation. Although the platelet count of their mother had been normal during pregnancy, the twins had severe thrombocytopenia; the platelet counts were 10×109/l for the first child and 9×109/l for the second child. Ultrasonography revealed subependymal hemorrhage in both children. Despite repeated blood transfusions, their thrombocytopenia persisted for 81 days. Antibodies reactive to their father's HLAs, which have not yet been reported as a Japanese trait, were detected in the maternal serum. This finding, together with the positive result of cross-matching using leukocytes from their father and sera from their mother, led us to diagnose their conditions as NAIT due to anti-HLA antibodies. In conclusion, we should be strongly aware that NAIT due to anti-HLA antibodies can be a potential cause of thrombocytopenia, particularly in a child of an international marriage, as different HLAs based on ethnic diversity might be transferred via the placenta.
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