Kenshi Furusho

HIGH-DOSE INTRAVENOUS GAMMAGLOBULIN FOR KAWASAKI DISEASE

The ability of high-dose intravenous gammaglobulin (IVGG) to prevent the coronary artery lesion of Kawasaki disease has been studied in a multicentre controlled trial of IVGG plus aspirin versus aspirin alone, aspirin being the conventional treatment for Kawasaki disease. Patients were allocated at random to aspirin (45 cases) or IVGG (40 cases), there being no significant intergroup differences in age, sex ratio, duration of disease until the start of treatment, or severity. The development of coronary artery dilatation was monitored by two-dimensional echocardiography. Within 29 days of the onset of the disease, this lesion had developed in 19 cases (42%) in the aspirin group and in 6 cases (15%) in the IVGG group. There were no new instances of this lesion: in the period 30-60 days coronary artery dilatation persisted in 14 and 3 cases, respectively. In patients found to have echocardiographic abnormalities selective coronary arteriography was done 30-60 days after onset of Kawasaki disease and the lesion was confirmed in 1 of the 6 cases in the IVGG group and in 11 of the 19 controls. High-dose IVGG seems to reduce the frequency of coronary artery abnormalities in patients with Kawasaki disease.

Genetic polymorphism of the CYP2C subfamily and its effect on the pharmacokinetics of phenytoin in Japanese patients with epilepsy

To examine the genetic polymorphism of CYP2C9 and CYP2C19 and its effect on the pharmacokinetics of phenytoin among 44 Japanese patients with epilepsy.

Increase in nitric oxide in the hypoxic–ischemic neonatal rat brain and suppression by 7-nitroindazole and aminoguanidine

We measured the changes in nitric oxide (NO) metabolites in the brains of neonatal rats with hypoxic-ischemic damage. There were two peaks of NO metabolites in the lesioned side of the cortex without treatment: one during hypoxia and the other during the re-oxygenation period. Prehypoxic treatment with 7-nitroindazole, a selective neuronal NO synthase inhibitor, suppressed both peaks of NO metabolites, whereas prehypoxic treatment with aminoguanidine, a selective inducible NO synthase inhibitor, partially suppressed only the peak in the re-oxygenation period. These data suggest different roles of neuronal and inducible NO synthases in the pathogenesis of hypoxic-ischemic encephalopathy.

Unfavorable effects of growth hormone therapy on the final height of boys with short stature not caused by growth hormone deficiency

A group of 18 boys with non-growth hormone (GH)-deficient short stature without GH therapy (group A) and another group of 9 boys with non-GH-deficient short stature with GH therapy in doses of 0.5 IU (0.17 mg)/kg per week administered 5 to 6 times weekly (group B) were observed until they reached their final height. The mean duration of GH therapy was 4.2 years (range 3.2 to 5.0 years). These two groups were matched with respect to their standard deviation score (SDS) for bone age at the start of observation. Mean +/- SD of the final height for group A and group B was 162.0 +/- 5.4 cm and 154.2 +/- 4.2 cm, respectively. During the prepubertal period, height SDS for bone age of these two groups was not affected by GH therapy. During the pubertal period, however, height SDS for bone age remained constant for group A but decreased gradually for group B. Our observation indicates that for boys with non-GH-deficient short stature GH therapy does not improve height SDS for bone age during the prepubertal period, and in fact reduces it during the pubertal period, possibly resulting in a shorter final height than might have been attained naturally.

Increased neurons containing neuronal nitric oxide synthase in the brain of a hypoxic-ischemic neonatal rat model.

We evaluated the temporal profile of the number of neurons containing neuronal nitric oxide synthase (nNOS neurons) in the brain of a neonatal hypoxic-ischemic rat model. Hypoxic-ischemic insults were produced in the brains of 7-day-old rat pups using a combination of unilateral carotid artery ligation and hypoxic (8% oxygen) exposure. Sections of brain from rats killed at 0-24 h after the onset of hypoxia were stained immunohistochemically using a polyclonal anti-nNOS antibody. Histological changes of neuronal injury were evaluated in the adjacent Nissl stained sections. The number of nNOS neurons in the hemisphere ipsilateral to the carotid ligation was significantly increased (P < 0.05) at 3 h, when the neuronal injury consisted of clusters of degenerating hyperchromic neurons. Neuronal degeneration and an increased number of nNOS neurons were seen only in the ipsilateral hemisphere and the increase was most prominent in the dorsolateral area of the striatum. The increase in the number of nNOS neurons continued at 6 h, when the area of neuronal injury continued to expand. At 24 h, the neuronal injury was diffuse, and the number of nNOS neurons on the ipsilateral side significantly decreased. The increase of the number of nNOS neurons in the early phase of neonatal neuronal injury suggests its possible involvement in the hypoxic-ischemic injury. The delineation of its role in neuronal injury may lead to an improvement in managing neonatal hypoxic-ischemic brain injury.

Surveys on the Prevalence of Pediatric Bronchial Asthma in Japan: A Comparison between the 1982, 1992, and 2002 Surveys Conducted in the Same Region Using the Same Methodology

BACKGROUND We conducted and reported the first (1982; 55,388 subjects), and second (1992; 45,674 subjects), epidemiological surveys conducted on bronchial asthma in elementary students across 11 prefectures in western Japan. The 2 surveys were conducted in the same regions using the same methodology employing a modified Japanese version of the American Thoracic Society-Division of Lung Diseases (ATS-DLD) Epidemiology Questionnaire. We conducted the third survey in 2002, and compared the findings to those of previous studies. METHODS In the third survey, 37,036 students attending the same schools as in previous surveys (in 11 prefectures) were given the questionnaire. A total of 35,582 responses (96.1%) were collected. An ATS-DLD Epidemiology Questionnaire was also used in this study, and the findings were compared to those of previous studies. RESULTS 1. The prevalence of bronchial asthma (BA) in boys, girls, and all students was 3.8%, 2.5%, and 3.2%, respectively, for the first survey; 5.6%, 3.5%, and 4.6% for the second survey; and 8.1%, 4.9%, and 6.5% for the third survey. 2. A decline in the BA prevalence in older subjects which could be seen in the first survey was absent in the second and third surveys. There were no regional differences in the third survey. 3. The boys-to-girls ratio in the first, second, and third surveys was 1.5, 1.6, and 1.6, respectively. 4. BA was more prevalent among subjects with a past history of respiratory disease in infancy and those with a family history of allergic disease. 5. The prevalence of asthma symptoms and wheezing in the first, second, and third surveys was 7.1%, 9.8%, and 11.8%, respectively. 6. A comparison of the prevalence of other allergic diseases between the second and third surveys revealed a decrease in atopic dermatitis and an increase in allergic rhinitis, allergic conjunctivitis, and cedar pollinosis. CONCLUSIONS BA prevalence in the third survey increased 2.1 and 1.4 times respectively compared to the first survey and second survey, indicating an upward trend in all regions and age groups surveyed.

X-inactivation pattern in the liver of a manifesting female with ornithine transcarbamylase (OTC) deficiency

Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder. It is X‐linked and hemizygous new‐born males usually suffer fatal hyperammonemia. In contrast, carrier females manifest variable phenotypes, ranging from asymptomatic carriers to those with severe hyperammonemia. In order to understand the correlation between X‐inactivation status and the clinical phenotype of carrier females with this disorder, we analyzed the X‐inactivation pattern of peripheral blood leukocytes in a family consisting of a clinically normal mother and two daughters with severe manifestation. In addition, we obtained tissue samples from various parts of the liver of one of these daughters and analyzed X‐inactivation patterns and the residual OTC activities. The X‐inactivation of peripheral blood leukocytes was nearly random in these carrier females and showed no correlation with the disease phenotype. However, the X‐inactivation of the liver was much more skewed and correlated well with the OTC activity of all samples. Interestingly, the degree of X‐inactivation varied considerably, even within the same liver.

LIVING-RELATED LIVER TRANSPLANTATION AND NEUROLOGICAL OUTCOME IN CHILDREN WITH FULMINANT HEPATIC FAILURE

BACKGROUND Fulminant hepatic failure (FHF) in children is associated with high mortality under medical management. Living-related liver transplantation (LRLT) is an accepted measure to treat the children with end-stage liver disease. Reversibility of hepatic encephalopathy is crucial for the quality of life among the survivors after transplantation. METHODS A retrospective review was made of the records of children undergoing LRLT at this hospital between May 1992 and November 1996. RESULTS Eleven children with FHF underwent emergency LRLT. The mean age was 5 years (range, 2 months to 15 years). The indication for transplantation was persistent or worsening hepatic encephalopathy and severe coagulopathy, despite repeated plasma exchanges or exchange transfusions. The cause of FHF was non-A, non-B hepatitis in seven children, hepatitis B in two children, herpes simplex virus hepatitis in one child, and fulminant Wilsons disease with intravascular hemolysis in one child. The grade of hepatic encephalopathy was II in four children, III in two, and IV in five. The actuarial survival rate was 73% after a mean follow-up of 28 months (range, 13-67 months). Short-term neurological morbidity was present in two children with grade IV encephalopathy who also showed brain edema on cranial computed tomography. Eight survivors exhibited no long-term neurological deficit; the mean intelligence or developmental quotient was 97 (range, 86-110) at the end of the follow-up period. CONCLUSIONS LRLT is an effective option for the treatment of FHF in children. The long-term neurological status is satisfactory among survivors.

Elevated serum interferon γ and interleukin‐6 in patients with necrotizing lymphadenitis (Kikuchi's disease)

We investigated serum levels of interferon α, interferon γ, tumour necrosis factor α, interleukin‐2 (IL‐2) and interleukin‐6 (IL‐6) in patients with necrotizing lymphadenitis (Kikuchis disease) (NL). Four male patients, diagnosed as having NL following biopsy of the affected lymph nodes and by the clinical course, were included in this study. All four patients had higher than normal serum interferon γ and IL‐6 levels during the acute phase, which returned to normal levels during the convalescent phase. Interferon α, tumour necrosis factor α and IL‐2 were, however, within the normal ranges. Our findings indicate the possibility that interferon γ and IL‐6 may play an important role in the pathogenesis of NL.

Tacrolimus and myocardial hypertrophy.

Tacrolimus has been used as an immunosuppressive agent in the transplantation of all solid organs. Tacrolimus-induced hypertrophic cardiomyopathy has been reported to be an unusual but serious complication. To elucidate the effects of tacrolimus on myocardial hypertrophy, we studied the relationship between the blood levels of tacrolimus and cardiac wall thickening. Our findings demonstrated that tacrolimus-induced myocardial hypertrophy correlated with tacrolimus blood levels, and that myocardial hypertrophy induced by tacrolimus was reversible. However, no patients developed clinically significant symptoms related to myocardial hypertrophy.