Serum sodium level is inversely correlated with body temperature in children.

BACKGROUND: Several studies have demonstrated that non-osmotic antidiuretic hormone activity contributes to the development of hyponatremia in children with common febrile diseases. However, the relationship between hyponatremia and body temperature has remained unclear. We therefore examined this relationship in children with common diseases. METHODS: In this retrospective case study based on a chart review, 1,973 children presenting with acute illnesses at Hirakata City Hospital between November 2008 and October 2009, and for whom blood test data were available, were enrolled. The median age of this cohort was 2.7 years and the mean serum sodium concentration was 136.4 mEq/L; 454 patients showed hyponatremia (<135 mEq/L). The patients were classified into four groups on the basis of body temperature, <37 °C, 37 °C (37.0-37.9 °C), 38 °C (38.0-38.9 °C) and ≥39 °C, and their serum sodium concentration was compared. RESULTS: The mean sodium level was significantly lower in febrile (135.9 mEq/L) than in non-febrile (138.5 mEq/L) patients. The mean serum sodium levels in the four temperature groups were, in ascending order, 138.5 mEq/L (95% CI, 138.3-138.8 mEq/L), 137.3 mEq/L (137.1-137.5 mEq/L), 136.1 mEq/L (135.8-136.3 mEq/L) and 134.6 mEq/L (134.4-134.9 mEq/L), respectively. The serum sodium level in each individual temperature range became significantly lower as body temperature increased (P < 0.001). CONCLUSIONS: There is a clear inverse correlation between serum sodium level and body temperature in children with common febrile diseases, and fever may play an important role in this relationship.

Efficacy of a mitochondrion-targeting agent for reducing the level of urinary protein in rats with puromycin aminonucleoside-induced minimal-change nephrotic syndrome.

BACKGROUND: Oxidative stress is a major factor responsible for minimal-change nephrotic syndrome (MCNS), which occurs most commonly in children. However, the influence of oxidative stress localized to mitochondria remains unclear. We examined the effect of a mitochondrion-targeting antioxidant, MitoTEMPO, in rats with puromycin aminonucleoside (PAN)-induced MCNS to clarify the degree to which mitochondrial oxidative stress affects MCNS. MATERIALS AND METHODS: Thirty Wistar rats were divided into three groups: normal saline group (n = 7), PAN group (n = 12), and PAN + MitoTEMPO group (n = 11). Rats in the PAN and PAN + MitoTEMPO groups received PAN on day 1, and those in the PAN + MitoTEMPO group received MitoTEMPO on days 0 to 9. Whole-day urine samples were collected on days 3 and 9, and samples of glomeruli and blood were taken for measurement of lipid peroxidation products. We also estimated the mitochondrial damage score in podocytes in all 3 groups using electron microscopy. RESULTS: Urinary protein excretion on day 9 and the levels of lipid peroxidation products in urine, glomeruli, and blood were significantly lower in the PAN　+　MitoTEMPO group than in the PAN group (p = 0.0019, p = 0.011, p = 0.039, p = 0.030). The mitochondrial damage score in podocytes was significantly lower in the PAN　+　MitoTEMPO group than in the PAN group (p <0.0001). CONCLUSIONS: This mitochondrion-targeting agent was shown to reduce oxidative stress and mitochondrial damage in a MCNS model. A radical scavenger targeting mitochondria could be a promising drug for treatment of MCNS.

Acetaminophen and Febrile Seizure Recurrences During the Same Fever Episode.

OBJECTIVES: To confirm the safety of using acetaminophen for febrile seizures (FSs) and to assess its efficacy in preventing FS recurrence during the same fever episode. METHODS: In this single-center, prospective, open, randomized controlled study, we included children and infants (age range: 6-60 months) with FSs who visited our hospital between May 1, 2015, and April 30, 2017. The effectiveness of acetaminophen was examined by comparing the recurrence rates of patients in whom rectal acetaminophen (10 mg/kg) was administered every 6 hours until 24 hours after the first convulsion (if the fever remained >38.0°C) to the rates of patients in whom no antipyretics were administered. No placebo was administered to controls. The primary outcome measure was FS recurrence during the same fever episode. RESULTS: We evaluated 423 patients; of these, 219 were in the rectal acetaminophen group, and 204 were in the no antipyretics group. In the univariate analysis, the FS recurrence rate was significantly lower in the rectal acetaminophen group (9.1%) than in the no antipyretics group (23.5%; P < .001). Among the variables in the final multiple logistic regression analysis, rectal acetaminophen use was the largest contributor to the prevention of FS recurrence during the same fever episode (odds ratio: 5.6; 95% confidence interval: 2.3-13.3). CONCLUSIONS: Acetaminophen is a safe antipyretic against FSs and has the potential to prevent FS recurrence during the same fever episode.

Clinical features in a series of 258 Japanese pediatric patients with thrombotic microangiopathy.

BACKGROUND: Thrombotic microangiopathy (TMA) includes hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). This study examined the epidemiological characteristics of pediatric patients with TMA classified according to etiology. METHODS: The survey evaluated 258 Japanese pediatric patients diagnosed with TMA between 2012 and 2015. RESULTS: The primary diseases responsible for TMA were categorized as TTP (15 cases), Shiga toxin-producing Escherichia coli-associated HUS (STEC-HUS) (166 cases), atypical HUS (aHUS) (40 cases), and secondary TMA (27 cases). The remaining 10 cases were unable to be classified to one of the four categories of the primary disease. Renal replacement therapy was required in the acute phase in 103 patients with TMA, including 65 with STEC-HUS, 22 with aHUS, two with TTP, 10 with secondary TMA, and four unclassified cases. The last observational findings were normal renal function in 95 patients and chronic kidney disease (CKD) stage 1 in 62. For 31 patients, chronic renal insufficiency (CKD stage 2-5) persisted, including four patients with end-stage kidney disease (CKD stage 5). Seventeen patients suffered recurrence of TMA, and eight patients died. CONCLUSION: This study clarified differences in the relative proportions of primary diseases between patients from Japan and North America and Europe. The difference may be attributable to the lower estimated incidence of STEC-HUS in Japan.

Prognostic factors in the early phase of acute encephalopathy.

BACKGROUND: Neurological sequelae occur in 40% of patients with acute encephalopathy (AE). The early prediction of poor outcomes is critical to the initiation of appropriate treatment. The aim of the present study was therefore to elucidate prognostic factors that can be quickly and feasibly evaluated on hospital admission in patients with AE. METHODS: We analyzed data from 51 AE patients admitted to Hirakata City Hospital between January 2005 and December 2014. Age at onset, sex, underlying disease, status epilepticus (SE), presence of benzodiazepine-resistant SE (BZD-resistant SE), and basic blood serum parameters on admission were evaluated in relation to each patient's outcome. RESULTS: On univariate analysis age at onset, BZD-resistant SE, and serum aspartate aminotransferase (AST), alanine aminotransferase, lactate dehydrogenase, and platelet count varied significantly according to outcome. On multivariate analysis age at onset (≤21 months), presence of BZD-resistant SE, and AST (≥46 IU/L) were identified as independent variables associated with poor outcome. CONCLUSION: Age at onset, presence of BZD-resistant SE, and AST are associated with a poor prognosis in AE.

Clinical characteristics of rotavirus gastroenteritis with urinary crystals.

BACKGROUND: Rotavirus gastroenteritis is severe and often results in dehydration and pre-renal azotemia. In addition, some patients with acute obstructive uropathy due to ammonium acid urate stones, developing approximately 6-7 days after the onset of rotavirus gastroenteritis, have been reported, mainly in Japan. The pathophysiological mechanism responsible for stone formation has not been clarified. In the present study, we investigated the clinical characteristics of these patients, and analyzed the pathophysiology underlying the formation of urinary stones. METHODS: A total of 164 patients were enrolled. All had acute gastroenteritis due to rotavirus infection and were treated at Osaka Medical College Hospital and affiliated hospitals between January 2009 and May 2011. All were younger than 15 years of age, and their laboratory data, including urinalysis, were available. RESULTS: Among the enrolled patients, 30 (20 boys and 10 girls aged 0.2-10 years; median, 1.5 years; interquartile range, 1-3 years) had crystals in their urine. Most of the patients were admitted approximately 2 days after onset of gastroenteritis and had hyperuricemia and aciduria. The crystals consisted mainly of uric acid, and rarely of ammonium acid urate. CONCLUSION: In order for ammonium acid urate stones to form in patients with acute obstructive uropathy associated with rotavirus gastroenteritis, prolonged continuous acidosis with hyperuricemia, might be necessary. Therefore, normalization of metabolic acidosis is important in order to prevent the onset of obstructive uropathy associated with rotavirus gastroenteritis.

Differential diagnosis of delirious behavior in children with influenza.

Delirious behavior (DB) in children infected with influenza virus is an important symptom associated with encephalopathy. As children with influenza-associated DB with encephalopathy may require therapy whereas children with influenza-associated DB without encephalopathy do not, distinguishing between these conditions is essential. To clarify these differences and identify the most common features of acute encephalopathy, we retrospectively reviewed the clinical course, laboratory data, magnetic resonance imaging (MRI) and electroencephalography (EEG) findings, therapy, and prognosis of 48 children with influenza exhibiting DB. Of the 48 children, 37 and 11 were diagnosed with influenza A and B, respectively. Moreover, 40 were diagnosed with DB without encephalopathy (DBNE group) and 8, with DB with encephalopathy (DBE group). Reversible splenial lesion (RESLE) was detected in 7 patients in the DBNE group, mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in 2 patients, and a mild form of acute encephalopathy with biphasic seizures and late reduced diffusion in 1 patient in the DBE group. Serum sodium levels <136mEq/L were observed in 28 cases. Disturbance of consciousness was observed in 25 cases, seizure in 20, and slow waves on EEG in 22. Methylprednisolone pulse therapy was administered in 8 cases. No cases of neurological sequelae were observed. Although most of the clinico-radiological features of the DBNE and DBE groups did not differ substantially, marked differences were observed in the age at onset, initial neurological symptoms, duration of DB, rate of seizure, and slowing of background activity on EEG. These differences should be considered when distinguishing between DBNE and DBE in children.

Molecular effect of a novel missense mutation, L266V, on function of ClC-5 protein in a Japanese patient with Dent's disease.

UNLABELLED: We report the use of three dimensional computational analysis of chloride channel 5 (ClC-5) based on a novel mutation, L266V, identified in a 15-year-old Japanese boy with Dent's disease. Since both leucine and valine are branched-chain amino acids, it has not been proved conclusively whether L266V mutation is actually responsible for the development of Dent's disease. In the present study using molecular analysis, we investigated the mechanism for loss of function of the ClC-5 protein resulting from the L266V mutation. Structural analysis of the normal ClC-5 transmembrane region using molecular modeling showed that the two respective Leu266 residues were located at the interface of the dimer formed by the aligned ClC-5 monomers. The Leu266 side-chains were positioned close to each other through hydrophobic interaction, resembling two interconnecting hooks. When Leu266 was replaced by a valine residue, the hydrophobic interaction between the CLC-5 monomers was reduced, and dimer formation was impaired. This computer simulation analysis has thus provided strong evidence for the important role of Leu266 in the dimerization of human ClC-5 in membranes. CONCLUSION: The finding of the present study suggest that computational modeling and molecular analysis could be an alternative to labor-intensive in vitro functional studies.