Kaoru Obinata

Effect of Taurine on the Fatty Liver of Children with Simple Obesity

This study elucidated the effect of taurine on fatty liver in simple obesity. Taurine was orally administered to 10 children with fatty liver. During taurine administration, the CT numbers of the liver, which were low in the beginning, increased. Serum ALT levels were improved, especially in those children whose weight was well controlled. Even in those who failed in weight control, serum ALT levels were slightly recovered. Ratios of glycine/taurine-conjugated bile acids were decreased. Thus, taurine was effective in treating fatty liver of children with simple obesity regardless of the success/failure of weight control. Taurine administration is considered to be helpful as an adjuvant therapy for fatty liver.

Genetic Basis of Patients with Bacille Calmette-Guérin Osteomyelitis in Japan: Identification of Dominant Partial Interferon-γ Receptor 1 Deficiency as a Predominant Type

Interferon (IFN)-gamma-mediated immunity plays an important role in host defense against intracellular pathogens, especially mycobacteria. Six Japanese children with bacille Calmette-Guérin (BCG) osteomyelitis were evaluated (1 disseminated, 3 multiple, and 2 solitary types) for mutations of genes involved in interleukin-12-dependent, IFN-gamma-mediated immunity. Heterozygous small deletions with frameshift (818del4 and 811del4) that are consistent with the diagnosis of partial dominant IFN-gamma receptor 1 (IFN-gammaR1) deficiency were detected in 3 unrelated patients. Expression of IFN-gammaR1 on monocytes was significantly increased in all 3 patients. Screening of family members with recurrent and disseminated mycobacterial infections found the identical deletion in 1 of the fathers. Antimycobacterial treatment was effective in these patients and resulted in good clinical outcome. This study demonstrated that partial dominant IFN-gammaR1 deficiency was the most common in Japanese patients who showed predisposition to curable BCG osteomyelitis.

Ursodeoxycholic acid therapy in the treatment of biliary atresia.

The prognosis of operated biliary atresia in the cases with bile excretion chiefly depends upon the prevention of ascending cholangitis. An antibiotic is therefore intravenously administered during the early postoperative phase, but cannot be used over a long period. In the cases showing satisfactory bile excretion after operation, ascending cholangitis is rare because of rapid disappearance of jaundice. Regarding this, the authors prescribed ursodeoxycholic acid (UDCA) at 10-15 mg/kg/day to 6 infants with biliary atresia for several weeks after operation, and then determined the effects of UDCA in improving jaundice and bile excretion. As a result, serum bilirubin and serum total bile acid (STBA) levels were decreased in 4 of the 6 infants. In the remaining 2 infants, their STBA levels showed no decrease, but were rather increased; these infants subsequently died of hepatic failure. These results suggested that UDCA is useful in the treatment of cholestasis associated with biliary atresia in the cases attaining postoperative bile excretion. It was also suggested that the treatment with UDCA should be stopped when the STBA levels increased after the beginning of the treatment. Therefore, it was thought that STBA levels measured during UDCA therapy could serve as a good indicator of the choleretic effect of UDCA.

Kawasaki disease followed by haemophagocytic syndrome

Sir: Ohga et al. [6] reported the development of haemophagocytic syndrome (HPS) in an infant during the recurrent evolution of Kawasaki disease (KD). We have recently seen a similar course of this rare association. A 1-year-old Japanese girl was admitted to our hospital with a nonexudative conjunctival injection, a polymorphous rash, and fever for 3 days. The perinatal period and past medical history were unremarkable. On admission, blood hyperleucocytosis and increased C-reactive protein (CRP) prompted treatment with antibiotics, acetylsalicyclic acid, and dipyridamole because of the possibility of a streptococcal infection. Nevertheless, fever persisted with redness of the pharynx and cervical adenopathy; when indurated oedema of hands and feet became manifest, the diagnosis of KD was made. She was given 200 mg/kg of intravenous immunoglobulin (IVIG) on days 11, 12, and 13 after admission. Although afebrile up to day 18 (see Table 1) she developed again fever afterwards, up to 40.6°C on day 24, with at the same time recurrence of skin rash, conjunctival injection, and cervical lymphadenopathy. Marked hepatosplenomegaly appeared. Blood demonstrated again hyperleucocytosis and increased levels of CRP Fig. 1 Bone marrow smear of the patient (Wright-Giemsa Stain). Arrow indicates a haemophagocytic histiocyte

Evaluation of psychosomatic stress in children by measuring salivary chromogranin A.

Aim: To investigate the usefulness of salivary chromogranin A (CgA) and cortisol as stress markers, and the effects of distraction on the suppression of stress in children. Methods: We examined salivary CgA and cortisol responses before and after venipuncture in hospitalized children with and without distraction using a kaleidoscope. Results: Salivary CgA levels immediately after venipuncture were significantly higher than those immediately before it, and at 60 min after venipuncture they were significantly lower than those immediately after it. However, salivary cortisol showed no significant differences at any of the three time points. In contrast, distracted by the kaleidoscope, there were no significant differences in salivary CgA and cortisol levels at all three time points.

Human Herpesvirus-6 (HHV-6)-Associated Hemophagocytic Syndrome

Virus-associated hemophagocytic syndrome (VAHS) is characterized by histiocytic proliferation and phagocytosis triggered by virus infections. Viruses in the herpes group, especially the Epstein-Barr virus (EBV), are well known to cause VAHS; however, the relationship between this syndrome and human herpesvirus-6 (HHV-6) infection has rarely been reported. In this study, we describe a 23-month-old girl who exhibited typical manifestations of VAHS associated with HHV-6 infection. To the best of our knowledge, this case is the fifth reported case in the English literature.

Sulfated and Nonsulfated Bile Acids in Urine of Patients with Biliary Atresia: Analysis of Bile Acids by High-Performance Liquid Chromatography

Summary To elucidate urinary bile acid patterns in patients with biliary atresia (BA), 15 sulfated and nonsulfated bile acids in urine were separately measured by high-performance liquid chromatography. This relatively simple technique for fluorescence detection utilizes the enzyme 3α-hydroxysteroid dehydrogenase (3α-HSD) to reveal urinary bile acid patterns. By this method, recovery rates of sulfated and nonsulfated bile acids in urine were satisfactory, and this analysis was shown to be applicable to clinical situations. In 10 patients with BA, the mean level of total bile acids in urine (23.35 ± 18.51 μmol/day) was seven times higher than the mean level in eight normal infants (3.05 ± 2.05 μmol/day). In the infants with BA, the mean level of total sulfated bile acids was about half of the total bile acid level. The main components of urinary nonsulfated bile acids in BA were glycocholic acid (6.21 ± 5.55 μmol/day) and taurocholic acid (2.28 ± 1.33 μmol/day), whereas the main components of the urinary sulfated bile acids were glycochenodeoxycholic acid (4.58 ± 6.97 μmol/day) and taurochenodeoxycholic acid (3.67 ± 3.54 μmol/day). Chenodeoxycholic acid, which is relatively toxic to the liver, may more easily be conjugated with sulfate and, hence, excreted into urine at a faster rate than cholic acid. Marked individual variations in urinary bile acid patterns were observed not only in BA patients but also in normal controls.

Clinical significance of the serum surfactant protein D and KL-6 levels in patients with measles complicated by interstitial pneumonia.

Abstract To examine the value of surfactant protein D and KL-6 as markers for the diagnosis and the severity of interstitial pneumonia caused by measles infection, surfactant protein D, KL-6 and lactic acid dehydrogenase were measured serially in three patients with measles complicated by interstitial pneumonia as compared to ten measles infected patients without interstitial pneumonia. The serum surfactant protein D and KL-6 levels were higher in patients with measles and interstitial pneumonia as compared to those with measles without interstitial pneumonia. In patients with measles and interstitial pneumonia, the respiratory distress and the alveolar-arterial oxygen differences improved after steroid pulse therapy while the serum surfactant protein D level decreased dramatically under the cut-off level and earlier than the KL-6 level. On the contrary, the serum KL-6 level increased transiently and it took longer to decrease below the cut-off level as compared to the pattern observed for serum surfactant protein D. The serum lactic acid dehydrogenase level changes were between those of the surfactant protein D and KL-6 levels. Conclusion Surfactant protein D and KL-6 are easily measured and useful markers for the diagnosis of interstitial pneumonia caused by measles infection. Early decrease of surfactant protein D contrasts with the transient increase of KL-6 levels after prednisolone pulse therapy.

Serum concentrations of glucuronidated and sulfated bile acids in children with cholestasis

Serum concentrations of nonglucuronidated-nonsulfated, glucuronidated, and sulfated bile acids in 9 control children and 16 children with cholestasis were quantitated by mass fragmentography. Total bile acid levels in control children were 19.55 +/- 2.78 mumol/liter (mean +/- SEM), and glucuronidated and sulfated bile acids comprised 2.6 +/- 0.5 and 17 +/- 3.1%, respectively. In 9 patients with congenital biliary atrasia, total bile acid levels were 167.34 +/- 11.18 mumole/liter of which 2.1 +/- 0.3% were glucuronidated and 15 +/- 1.4% were sulfated. Lithocholic and 3 beta-hydroxy-5-cholenoic acids, which have hepatotoxic effects, were presented in only small amounts in cholestatic children, and they were almost all glucuronidated or sulfated. The percentages of glucuronidated bile acids in control and cholestatic children were lower than in healthy and cholestatic adults, which may be explained by the lower activity of UDP-glucuronyltransferase in neonatal liver.

A boy with a severe phenotype of succinic semialdehyde dehydrogenase deficiency

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder affecting γ-aminobutyric acid degradation. We describe here a boy with a severe phenotype of SSADH deficiency. He was referred because of a developmental delay at 4 months of age. At the age of 8 months, severe seizures developed. The diagnosis of SSADH deficiency was confirmed by an increase in 4-hydroxybutyric acid and heteroallelic mutation in the ALDH5A1 gene. His seizures were successfully treated with high-dose phenobarbital, and the electroencephalogram (EEG) abnormalities were ameliorated. However, the patient showed a degenerative clinical course with severe neurological deficits. A magnetic resonance imaging (MRI) scan revealed abnormal high intensities in the putamina and caudate nuclei on T2-weighted images, followed by marked atrophic changes. The clinical manifestation of our patient indicates the wide variety of SSADH deficiency phenotypes.