Birth order and paediatric allergic disease: A nationwide longitudinal survey.

BACKGROUND: Environmental factors seem to be related to the incidence of allergic disease. Children with a later birth order are often exposed to environments, where pathogens and endotoxins can be found, and thus have a higher risk of developing infectious diseases. Therefore, birth order is regarded as an indicator that reflects post-natal environment. However, longitudinal studies are limited on this subject. This study sought to elucidate the relationships between birth order and allergic disease. METHODS: From a nationwide longitudinal study that followed children born in 2001 (n = 47 015), we selected doctors' visits for 3 types of allergic disease-bronchial asthma, food allergy and atopic dermatitis-from infancy to 12 years of age and conducted binomial log-linear regression analysis to evaluate the associations between birth order and these diseases. We adjusted for the child and parental factors and estimated risk ratio (RR) and 95% confidence interval (CI) for each outcome. RESULTS: The associations between birth order and bronchial asthma were diverse; later birth order increased the risk in early childhood, but decreased the risks during school age. For example, the adjusted RR comparing third-born or higher and first-born children was 1.19 (95% CI, 1.05-1.35) between 30 and 42 months of age, but was 0.76 (95% CI, 0.65-0.89) between 10 and 11 years. Later birth order was generally protective for food allergy but increased the risk of atopic dermatitis. CONCLUSION: The influence of birth order depended on the type of allergic disease and the childhood period. Childhood is unique in terms of physical and immunological development, and the immune response to the post-natal environment in childhood appears to be heterogeneous.

Nitrite/nitrate in nasal lavage fluid reflects nasal symptoms after a single nasal allergen provocation in patients with seasonal allergic rhinitis

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Reversible splenial lesion with restricted diffusion in a wide spectrum of diseases and conditions.

OBJECTIVE: Reversible lesion in the central area of the splenium of the corpus callosum (SCC) is a unique phenomenon occurring particularly in patients with encephalitis or encephalopathy and in patients receiving antiepileptic drugs (AED). We report MR imaging findings, clinical courses, and outcomes in eight patients with various diseases and conditions. MATERIALS AND METHODS: Eight patients with a reversible SCC lesion with transiently restricted diffusion were reviewed retrospectively. Diseases and conditions that were associated with a reversible lesion included epilepsy receiving AED (n=1), seizure from eclampsia receiving AED (n=1), mild infectious encephalitis (n=2), hypernatremia resulting in osmotic myelinolysis (n=1), and neoplasm (n=3) such as acute lymphocytic leukemia, spinal meningeal melanocytoma, and esophageal cancer. We evaluated MR imaging findings and clinical findings. RESULTS: Seven patients had isolated SCC lesions; one patient with osmotic myelinolysis showed additional parenchymal lesions. The reversible SCC lesion shape was oval (n=6) or extended (n=2). The mean apparent diffusion coefficient value of the splenial lesion was 0.40+/-0.16 x 10-3 mm2/s, ranging from 0.22 to 0.64 x 10-3 mm2/s. In a patient with osmotic myelinolysis, additional white matter lesions, shown as restricted diffusion, were revealed as not reversible on follow-up MR imaging. Neurological courses and outcomes were good in seven patients with isolated SCC lesions, but poor in one with osmotic myelinolysis. CONCLUSION: Reversible SCC lesion with restricted diffusion is apparent in a wide spectrum of diseases and conditions. Neurological courses and outcomes are good, particularly in patients with isolated SCC lesions. Knowledge of MR imaging findings and the associated spectrum of diseases and conditions might prevent unnecessary invasive examinations and treatments.

Widening spectrum of a reversible splenial lesion with transiently reduced diffusion.

Four patients with encephalitis/encephalopathy and parenchymal lesions accompanying reversible splenial lesions were retrospectively evaluated. In 3 patients, reversible lesions with transiently reduced diffusion were seen in the splenium and symmetrically in the peripheral frontoparietal white matter, clinical signs and symptoms were mild, and recovery was complete. These and previous observations suggest a less severe course and outcome for patients with reversible lesions isolated to the splenium or to the splenium and peripheral frontoparietal white matter.

Quantitative unspun-urine microscopy as a quick, reliable examination for bacteriuria.

The diagnosis and treatment of urinary infection are often delayed, causing renal damage, largely because of the unavailability of quick, accurate, diagnostic examinations. Three hundred and twenty-five urine samples from 130 patients were examined for significant bacteriuria using the standard culture method. The urine samples were also examined using the Gram-stain method and quantitative unspun-urine microscopy. When particles could not be distinguished definitely as bacilli by quantitative microscopy, the unspun urine was examined on a slide glass using oil-immersion microscopy at x 1000 magnification. Significant bacteriuria in 37 urine samples was detected by bacterial culture. Using quantitative microscopy, rods were found in 30, cocci in a chain in 3, and indefinite particles in 44 samples. In the 44 indefinite samples, oil-immersion microscopy was able to distinguish rods in one, cocci in a chain in one, cocci in a cluster in two, and negative in 40, which were confirmed by culture as rods, streptococci, staphylococci, and negative, respectively. The quantitative microscopy method was similarly reliable (94.6% sensitivity, 99.3% specificity) for diagnosis of significant bacteriuria when compared with the Gram-stain method (89.2% sensitivity, 98.6% specificity). Quantitative unspun-urine microscopy, confirmed by oil-immersion, is a quick, reliable method for diagnosis of significant bacteriuria, and is considered to be useful for early diagnosis of urinary infection.

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion.

OBJECTIVE: To clarify whether patients with clinical diagnoses of encephalitis/encephalopathy with a reversible lesion in the splenium of the corpus callosum (SCC) share common clinical features. METHODS: Possible encephalitis/encephalopathy patients with a reversible isolated SCC lesion on MRI were collected retrospectively. Their clinical, laboratory, and radiologic data were reviewed. RESULTS: Fifteen encephalitis/encephalopathy patients with a reversible isolated SCC lesion were identified among 22 patients referred for this study. All 15 patients had relatively mild clinical courses. Twelve of the 15 patients had disorders of consciousness. Eight patients had seizures, and three of them received antiepileptic drugs. All 15 patients clinically recovered completely within 1 month (8 patients within a week) after the onset of neurologic symptoms. The SCC lesion was ovoid in six patients; it extended irregularly from the center to the lateral portion of SCC in the other eight patients. Homogeneously reduced diffusion was seen in all seven patients who underwent diffusion-weighted imaging. There was no enhancement in the five patients so examined. The SCC lesion had completely disappeared in all patients at follow-up MRI exams between 3 days and 2 months after the initial MRI (within 1 week in eight patients). CONCLUSION: The clinical features among the affected patients were nearly identical, consisting of relatively mild CNS manifestations and complete recovery within 1 month.

Oxidative and nitrosative stress in acute renal ischemia.

Generation of reactive oxygen species and nitric oxide in hypoxia-reperfusion injury may form a cytotoxic metabolite, peroxynitrite, which is capable of causing lipid peroxidation and DNA damage. This study was designed to examine the contribution of oxidative and nitrosative stress to the renal damage in ischemic acute renal failure (iARF). iARF was initiated in rats by 45-min renal artery clamping. This resulted in lipid peroxidation, DNA damage, and nitrotyrosine modification confirmed both by Western and immunohistochemical analyses. Three groups of animals were randomly treated with an inhibitor of inducible nitric oxide synthase (NOS), L-N(6)-(1-iminoethyl)lysine (L-Nil), cell-permeable lecithinized superoxide dismutase (SOD), or both. Each treatment resulted in amelioration of renal dysfunction, as well as reduced nitrotyrosine formation, lipid peroxidation, and DNA damage, thus suggesting that peroxynitrite rather than superoxide anion is responsible for lipid peroxidation and DNA damage. Therefore, in a separate series of experiments, a scavenger of peroxynitrite, ebselen, was administered before the reperfusion period. This treatment resulted in a comparable degree of amelioration of iARF. In conclusion, the present study provides the first attempt to elucidate the role of peroxynitrite in initiation of the cascade of lipid peroxidation and DNA damage to ischemic kidneys. The results demonstrate that L-Nil, lecithinized SOD, and ebselen treatments improve renal function due to their suppression of peroxynitrite production or its scavenging, consequently preventing lipid peroxidation and oxidative DNA damage.

Significance of ACE genotypes and medical treatments in childhood focal glomerulosclerosis.

BACKGROUND: There is little information on the significance of angiotensin-converting enzyme (ACE) genotypes and medical treatments in children with primary focal segmental glomerulosclerosis (FSGS). METHODS: A multicenter retrospective study was performed on the role of ACE genotypes and medical treatments in 43 Japanese children with FSGS (20 males and 23 females), including 17 children who progressed to end-stage renal failure during the mean observation period of 6.9 +/- (SD) 5.0 years. RESULTS: The incidence of the D allele of the ACE gene was higher in the whole group of 43 children with FSGS and in a subgroup of 28 steroid-resistant FSGS children (p < 0.05) than in the 130 children of the healthy control group (0.48, 0.48, and 0.33, respectively). ACE genotypes did not affect renal survival in the whole FSGS group nor in the steroid-resistant subgroup. Among the 28 steroid-resistant children, treatment with ciclosporin was effective in delaying the development of end-stage renal failure (p = 0.044), independently of other treatment regimens. CONCLUSION: The present study of Japanese children with FSGS showed that the D allele of the ACE gene is associated with the development of FSGS, but not associated with the progression of FSGS which was greatly ameliorated with ciclosporin, irrespective of ACE genotypes.

Increased oxidative stress in childhood atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease of unknown etiology. To examine the involvement of impaired homeostasis of oxygen/nitrogen radicals in childhood AD, we compared the levels of urinary 8-hydroxy-2'-deoxyguanosine (marker of oxidative stress), nitrite/nitrate (marker of nitric oxide synthesis) and selenium (marker of selenium store) in 27 children with AD to those of 25 healthy control children. Urinary 8-hydroxy-2'-deoxyguanosine was significantly higher and nitrite/nitrate levels were significantly lower in patients with AD than in the control. Urinary selenium levels were similar in both groups. Our findings suggest that impaired homeostasis of oxygen/nitrogen radicals and increased oxidative stress are involved in the pathophysiology of childhood AD, and indicate that suppression of oxidative stress might be a potentially useful strategy for the treatment of AD.

Involvement of thioredoxin in the regulation of growth hormone secretion in rat pituitary cell cultures.

We report here an examination of the effect of thioredoxin (TRX) on the secretion of growth hormone (GH) from rat anterior pituitary cells in vitro. Treatment of rat pituitary cells with growth hormone-releasing factor (GRF), but not GH, led to a significant increase in intracellular TRX protein levels. GRF, recombinant human TRX (rhTRX), and a combination thereof were all shown to induce immediate GH secretion from pituitary cells, as evidenced by perifusion experiments. RhTRX, but not other reducing agents such as beta-mercaptoethanol and N-acetyl-L-cysteine, augmented GRF-stimulated and -unstimulated GH secretion from rat pituitary cells in a dose-dependent manner. RhTRX did not significantly affect the GH mRNA expression of pituitary cells stimulated in the presence or absence of GRF. In addition, rhTRX-augmented GH secretion was not significantly affected by the presence of cycloheximide. Collectively, these findings suggest that TRX is induced by stimulation with GRF and plays a regulatory role in GH secretion from rat anterior pituitary cells by enhancing the secretion of stored GH, rather than by the synthesis of GH.

Uroguanylin level in umbilical cord blood.

BACKGROUND: Uroguanylin is a novel natriuretic and diuretic peptide originally isolated from urine. METHODS: To determine whether uroguanylin has a physiologic role during the perinatal period, uroguanylin levels in umbilical cord plasma obtained at the time of delivery were measured by radioimmunoassay and compared with cord serum osmolality. RESULTS: Mean (+/- SD) cord plasma uroguanylin concentrations (8.8 +/- 2.1 fmol/mL) were higher compared with normal adult values. The extent of maturity, mode of delivery and gender did not appear to influence cord uroguanylin levels. The uroguanylin concentration had a significant positive correlation with cord serum osmolality. CONCLUSION: These findings support some regulatory role of this peptide in perinatal renal and cardiovascular adaptation.

No evidence for AT2R gene derangement in human urinary tract anomalies.

BACKGROUND: It has been recently found that mice, especially males, with a disrupted angiotensin type 2 receptor (AT2R) gene, which is located on the X-chromosome, often have a range of congenital anomalies of the kidney and urinary tract (CAKUT), including renal hypoplasia, and that Caucasian male patients with ureteropelvic junction stenosis (UPJ) and multicystic dysplastic kidneys frequently have A-G transition in intron 1 of the AT2R gene. We have previously found that renal hypoplasia is remarkably predominant in Japanese boys. METHODS: We investigated sex ratios for the frequency of each CAKUT. The frequency of the A-G transition between the controls and 66 Japanese boys with CAKUT were compared. There was renal hypoplasia in 16, UPJ in 17, vesicoureteral in 20, and other anomalies in 13. We also investigated whether any mutations in AT2R genes were detectable in patients with renal hypoplasia. RESULTS: In contrast to mice with a disruption of the AT2R gene, the male-to-female ratios in human patients proved to be considerably variable: 16 for renal hypoplasia, 2.1 for UPJ, 0.8 for vesicoureteral, and 1.2 for others. The frequency of the A-G transition was not different between the control population and the patients with CAKUT [31 of 102 (30%) vs. 23 of 66 (35%), respectively]. A sequencing study disclosed no mutations in nine boys with renal hypoplasia. CONCLUSIONS: These findings indicate that the AT2R gene may not play a major role in the development of renal hypoplasia and other CAKUT in humans, at least in the Japanese population.

Zero-birefringence polymer by the anisotropic molecule dope method.

We propose using the anisotropic molecule dope method for synthesizing a zero-birefringence polymer that showed no orientational birefringence at any orientation degree of polymer chains. In this method a rodlike molecule with polarizability anisotropy was chosen to compensate orientational birefringence. The zero-birefringence polymer was synthesized by doping of 3-wt.% trans-stilbene as an anisotropic molecule into poly(methyl methacrylate). The zero-birefringence at the 590-nm wavelength in the drawn film and the injection-molded plate made from the zero-birefringence polymer was confirmed by the rotating parallel nicols method. Furthermore, high transparency (37.2 dB/km) of the zero-birefringence polymer at the 633-nm wavelength was confirmed by the light-scattering measurement.

Older boys benefit from higher initial prednisolone therapy for nephrotic syndrome. The West Japan Cooperative Study of Kidney Disease in Children.

BACKGROUND: A long course of the initial prednisolone therapy has been shown to be more effective than standard-course therapy in reducing relapse rates in children with idiopathic nephrotic syndrome, but it is commonly accompanied by corticosteroid toxicities. There has been no study on prednisolone dosage for the effective treatment of nephrotic syndrome. METHODS: Sixty-eight children (42 boys and 26 girls) with an initial attack of nephrotic syndrome were randomly allocated into two different long-course treatment groups. Patients in Group 1 received a daily prednisolone dose of 60 mg/m2 for six weeks, followed by an alternate-day dose of 40 mg/m2 for six weeks. Patients in Group 2 had a daily dose of 40 mg/m2 instead of 60 mg/m2. RESULTS: Four children in each group did not respond within six weeks. Group 1 was associated with a significantly earlier response but more frequent corticosteroid toxicities than Group 2. Boys in Group 1 had a higher rate of sustained remission than boys in Group 2 (P = 0.0073), especially boys four years old or more (P = 0.0027), but girls did not show a significant difference (P = 0.863). Boys four years old or more in Group 1 had a course of frequent relapsing less often than those in Group 2 (2 of 13 vs. 6 of 8, P = 0.0075). CONCLUSION: These findings indicate that efficient prednisolone doses may vary between sexes and ages, and that a higher initial prednisolone therapy may be of greater benefit to older boys.

Efficacy of long-term azathioprine for relapsing nephrotic syndrome.

Seven patients who had an initial attack of nephrotic syndrome in childhood and had frequent relapses even after cyclophosphamide therapy were given a 2-year course of azathioprine. The mean annual relapse rates decreased from 2.4+/-0.5 in the year preceding azathioprine to 0.4+/-0.8 in the 1st and 2nd years after its initiation. All six patients who were observed for more than 6 months after discontinuation of the therapy were relapse free for this period. Average doses of prednisolone could also be decreased in the 2nd and subsequent years after the therapy. There were no significant toxic effects. Long-term azathioprine therapy may be well tolerated and effective for nephrotic patients with frequent relapses.

Increased oxidative stress in rats with chronic nitric oxide depletion: measurement of urinary 8-hydroxy-2'-deoxyguanosine excretion.

Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been reported to serve as a sensitive biomarker of oxidative stress. We examined the effect of chronic blockade of nitric oxide (NO) on urinary excretion of 8-OHdG in rats. Two types of NO synthase inhibitor were used: N(G)-nitro-L-arginine methyl ester (L-NAME) as a non-selective inhibitor and aminoguanidine (AG) as a selective inhibitor of the inducible isoform. Oral administration of L-NAME (20, 50 and 80 mg/dl of drinking water), but not AG (400 mg/dl), for 4 weeks induced systemic hypertension and a significant reduction in urinary excretion of NO2-/NO3-. Rats treated with L-NAME also showed a significant increase in urinary 8-OHdG excretion compared with the control animals. The effects of L-NAME (50 mg/dl) on blood pressure and urinary excretion of NO2/NO3- and 8-OHdG were restored by a large dose of L-arginine (2.0 g/dl). Chronic AG administration did not significantly alter urinary 8-OHdG excretion. On combining all the data, there was a significant negative correlation between urinary NO2-/NO,- and 8-OHdG. These observations suggest the importance of constitutive NO synthase activity in the maintenance of oxidant buffering capacity in rats. Oral administration of L-NAME may serve as a model of hypertension due to chronic NO deficiency with increased oxidative stress.

Methylenetetrahydrofolate reductase polymorphism in Kawasaki disease.

BACKGROUND: A genetic aberration in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (677 C to T substitution) has been shown to result in reduced enzyme activity. The hypothesis tested in the present study was that a higher proportion of Kawasaki disease (KD) patients with coronary artery lesions (CAL) would have the T677 allele compared with patients without CAL and healthy subjects. METHODS: Genotypes for MTHFR were determined in 75 KD patients (male:female ratio 52:23) and 238 healthy subjects (male:female ratio, 110:128) by the polymerase chain reaction and restriction fragment length polymorphism method. RESULTS: The results indicated that female KD patients had a significantly higher frequency of the TT genotype compared with female control subjects. In the female population, the frequency of the TT genotype in patients with initial coronary aneurysm was significantly lower than in patients without this manifestation. Analysis of the data for the male population showed that the frequency of the TT genotype in KD patients developing coronary stenosis, occlusion or myocardial infarction was higher than that in those without these manifestations, although the difference was statistically insignificant. CONCLUSIONS: The TT genotype may protect female KD patients against initial aneurysm formation and predispose male KD patients to severe coronary complications. Further large-scale studies may be required to confirm the contribution of homocysteine in the coronary sequelae of KD.