A novel method for predicting the unbound valproic acid concentration.

In this study, we constructed a prediction formula for unbound valproic acid (VPA) concentration that was more accurate and widely applicable than previously reported formulae. A total of 136 datasets from 75 patients were analyzed retrospectively. The median of free fraction of VPA was 0.16 (interquartile range: 0.07; range: 0.07-0.45). The parameter that combined total VPA concentration (CtVPA) and serum albumin (SA), (CtVPA [µM] - 2 × SA [µM]), was significantly related to the free fraction of VPA (r = 0.76, p < 0.001). We constructed a combined parameter-based prediction formula for unbound VPA concentration. Analysis using external datasets from patients without severe renal failure showed that the prediction errors of the unbound VPA concentration were lower than those of previously reported formulae. Although the previous formulae showed large prediction errors, especially in the specific range of CtVPA values, the constructed formula showed a weak trend with CtVPA or SA. The formula based on (CtVPA [µM] - 2 × SA [µM]) had high prediction accuracy and wide applicability in predicting the unbound VPA concentration in patients without severe renal failure.

Perioperative reactive oxygen species in infants with biliary atresia: A retrospective observational study.

Biliary atresia (BA) is a devastating cholestatic disorder of infants that presents during the first several months after birth due to an idiopathic obstruction to the bile flow. Without prompt diagnosis, Kasai portoenterostomy, and deliberate follow-ups, the resulting cholestasis leads to progressive hepatic failure. Oxidative stress is an abnormal phenomenon inside cells or tissues caused by a disturbance in the reactive oxygen species (ROS). We aimed to measure perioperative ROS in BA patients.Data are presented as median (25th, 75th percentiles). We evaluated 15 BA patients (age 55 [48, 69] days) and measured ROS; serum superoxide dismutase (SOD), urinary 8-iso prostaglandin F2α (8-iso-PGF2α) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) preoperatively and 30 days later to compare values with serum liver function tests and histologic grades of liver cholestasis. For compared BA patients, 4 normal subjects as control group (age 55 [27, 75] days) measured ROS and serum liver function tests.In BA patients, the preoperative serum SOD was 6.1 IU/mL (4.7, 7.2), urinary 8-iso-PGF2α was 1969 pg/mg Cre (1697, 2374), and urinary 8-OHdG was 37.1 ng/mg Cre (33.1, 53.7). At the postoperative day 30, the serum SOD was 5.2 IU/mL (4.2, 6.7), urinary 8-iso-PGF2α was 1761 pg/mg Cre (1256, 3036), and urinary 8-OHdG was 42.1 ng/mg Cre (29.65, 72.64). In ROS, there were no significant differences between the 2 periods. In control group, urinary 8-iso-PGF2α was significantly lower than that in preoperative BA patient group. However, other ROS were not significant differences between control group and BA patient group. The concentration of urinary 8-iso-PGF2α was positively correlated with total bilirubin and direct bilirubin levels (preoperatively: r = 0.6921, P = .0042 and r = 0.6639, P = .007, postoperatively: r = 0.6036, P = .0172 and r = 0.6464, P = .0092, respectively). The preoperative ROS were not correlated with histologic grades of liver cholestasis. Various factors such as liver inflammation, lipid malabsorption, and tissue disorders due to jaundice might affect the antioxidant activity and elevated urinary 8-iso-PGF2α. However, at least until 30 days later, urinary 8-OHdG as oxidative DNA damage might persist after the operation whether the cholestasis improved or not.

The management and outcome of pediatric blunt chest-abdominal injuries.

BACKGROUND: The aim of this study was to determine the frequency and nature of pediatric blunt chest-abdominal injuries (BCAIs) and to summarize their management, ranging from non-operative management (NOM), with or without angioembolization (AE), to surgical treatment. METHODS: This retrospective study included patients admitted to our hospital for BCAIs from January 1996 to December 2017. The age, injury pattern, organs of injury, outcome, and treatment were summarized. RESULTS: One hundred and thirty-two patients (98 males, 34 females, mean age 7.68 years ± 3.58, range 1-15 years) were included in the study. Their injuries resulted from motor-vehicle traffic incidents (n = 60), single-bicycle injuries (n = 16), falls (n = 33), sports (n = 10), assault (n = 6), abuse (n = 3), and others (n = 4). There were no injured organs in 31 cases, while there were 130 injured organs in 101 cases, including the liver (n = 42), spleen (n = 35), lung (n = 23), kidney (n = 13), intestine (n = 10), pancreas (n = 5), and adrenal gland (n = 2). Angiography (AG) was performed in 20 cases, and NOM with AE was performed in 16 cases, including 17 organs (liver injury [n = 9], splenic injury [n = 5], and kidney injury [n = 4]). Surgical treatment was performed in eight cases (splenic injury in one, pancreas injury in one, and intestinal injury in six). NOM without AE was performed in the other cases. CONCLUSIONS: The management of organ injury must take into consideration the management of integrated bleeding. It is recommended that children with severe organ injury are treated in dedicated trauma centers in which AE is available.

The herbal medicine Inchinko-to reduces hepatic fibrosis in cholestatic rats.

PURPOSE: Several studies have reported the herbal medicine Inchinko-to (ICKT) to have an antifibrotic effect which thus leads to an improvement of hepatic injury. However, there are still few reports of its use in the treatment of cholestatic liver disorder. The aim of this study was to clarify whether the administration of ICKT will ameliorate hepatic fibrosis and injury in cholestatic rats. MATERIALS AND METHODS: We performed bile duct ligation on 7-week-old male cholestatic Wistar rats and assigned them to one of three groups according to the method of treatment: (1) the SHAM group, (2) the NT-group (non-treatment group), and (3) the T-group (treatment-group). Rats in the T-group were orally administered ICKT (TJ-135) at a dose of 1 g/kg/day and were killed on the 17th postoperative day. We subsequently investigated the levels of fibrosis and various clinical markers through measurement of the following: serum levels of AST and ALT; tissue transforming growth factor-beta 1 (TGF-beta1); tissue inhibitor metalloprotease-1 mRNA (TIMP-1 mRNA) through real-time PCR analysis; and Azan staining and immunohistochemical staining of alfa-smooth muscle actin (alfa-SMA) to evaluate the degree of fibrosis. RESULTS: The levels of serum AST, serum ALT, and TGF-bata1 in the T-Group were significantly lower than those in the NT-Group. In addition, staining of Azan and alfa-SMA in the T-Group was significantly lower than those in the NT-Group. CONCLUSION: ICKT may help reduce hepatic fibrosis and injury by controlling stellate cell activation.

Thoracic lymphangiomatosis with massive chylothorax after a tumor biopsy and with disseminated intravenous coagulation--lymphoscintigraphy, an alternative minimally invasive imaging technique: report of a case.

Thoracic lymphangiomatosis in childhood is a rare disorder that frequently has poor response to medical therapy as well as a poor prognosis. This disease is often misdiagnosed, and a definitive diagnosis is usually delayed because of the rarity and slow course of the disease. No previous reports have so far described the usefulness of lymphoscintigraphy in the diagnosis of lymphangiomatosis, although some authors have reported the efficacy of lymphoscintigraphy for evaluating chylothorax. A 6-year-old boy presented with a diffuse mediastinal mass and received an open mediastinal biopsy for a definitive diagnosis, which led to the occurrence of massive chylothorax postoperatively. A diagnosis of lymphangiomatosis was finally made based on the lymphoscintigraphic findings demonstrating an obstruction of the thoracic duct. This report describes a rare case of thoracic lymphangiomatosis diagnosed at autopsy, and suggests that the minimally invasive technique of lymphoscintigraphy should be employed to obtain a definitive diagnosis at an early stage.

[Perioperative nutritional support from the viewpoint of risk management].

The nutritional condition of perioperative patients affects the results of surgical treatment. For a better prognosis, surgeons must always consider patients' nutritional status preoperatively. After first assessing the nutritional status, a regimen to improve and/or maintain proper nutrition should be selected taking symptoms and treatment procedure into consideration. Peripheral parenteral nutrition provides limited energy. If patients' nutritional status requires improvement and they must fast for a long-term, total parenteral nutrition should be administered. Parenteral nutrition is nonphysiologic therapy and may have severe complications. During the administration of enteral nutrition via a gastrointestinal fistula or nasogastric tube, vomiting and incorrect infusion due to the improper positioning of the feeding tube may occur. When administering nutrition therapy via a gastrostomy or intestinal fistula, care must be taken to determine the appropriate dose and infusion rate. To provide suitable nutritional therapy, our knowledge of the various options available must be expanded.

The herbal medicine daikenchuto ameliorates an impaired anorectal motor activity in postoperative pediatric patients with an anorectal malformation--a pilot study.

Fecoflowmetry (FFM) has been introduced to simulate natural anorectal evacuation. So far, few reports have described the effect of the herbal medicine Daikenchuto (DKT) on impaired anorectal motor function. The aim of this pilot study was to assess anorectal motor function by FFM in postoperatively impaired patients with an anorectal malformation (ARM) before and after administration of DKT. Six postoperative patients with ARM (mean age, 7.8 years) who complained of intractable constipation with soiling in spite of administration of magnesia as a laxative were assessed over an extended period. These patients received 0.3 g/kg/d of DKT for an average of 128 days. Evacuative rate and maximum fecal stream flow were seen to increase significantly after administration of DKT when compared with values before administration of DKT. In conclusion, DKT had a favorable clinical effect on anorectal motor function in postoperative patients with ARM.

Oxidative stress profile in the post-operative patients with biliary atresia.

BACKGROUND AND PURPOSE: Many post-operative patients with biliary atresia (BA) suffer from liver dysfunction, such as chronic inflammation even without jaundice after a Kasai's hepatic portoenterostomy. METHODS: The presence and degree of oxidative stress were evaluated in the post-operative patients with BA. Twelve outpatients who underwent a Kasai's hepatic portoenterostomy were evaluated. The active oxygen products, the rate of bioantioxidant, the markers of oxidative stress, and the degree of hepatic oxidative stress were examined by immunohistochemical staining of biopsied specimens. RESULTS: All of the oxidative stress markers in the post-operative patients with BA increased in comparison to those in the controls. Moreover, 8-OHdG immunohistochemical staining was positive in 84+/-4.8% in hepatic cells in the portal area in the post-operative patients with BA. CONCLUSION: The post-operative patients with BA were under increased oxidative stress, even if their liver dysfunction was mild without jaundice. Antioxidant therapy might be necessary to decrease of oxidative stress in the post-operative patients with BA.

A case of split notochord syndrome with congenital ileal atresia, the total absence of a colon, and a dorsal enteric cyst communicating to the retroperitoneal isolated ceca with a vesical fistula.

Split notochord syndrome (SNS) is an extremely rare anomaly. This report presents the case of a male infant with SNS associated with congenital ileal atresia and a dorsal enteric cyst communicating to the retroperitoneal isolated ceca with a vesical fistula. Dorsal fistulography and vesicography were useful and essential for the detailed study of the topology in this patient. The embryological mechanism and etiologic theories are discussed with a review of 19 cases reported in the literature.

Multiple ileal polyps associated with gastrointestinal perforation in a 2-day-old neonate.

We experienced a very rare case of a gastrointestinal perforation due to multiple ileal polyps. The patient was a 2-day-old boy who weighed 1,430 g at birth. At neonatal day 2 subdiaphragmatic free air was noted and an emergency operation was performed. During surgery a distended ileum approximately 5 cm in size was found approximately 40 cm distal from the ileocecum, and a perforation was discovered in the distended portion of the intestine. Approximately 8 cm of the ileum was resected, including the distended portion of the intestine, and an ileostomy was performed. Examination of the resected specimen revealed three pedunculated polyps with a perforation proximal to the polyps.

Nesidioblastosis treated successfully by 85% pancreatectomy.

Nesidioblastosis is a rare disorder in pediatric surgery. It is caused by hypertrophy and hyperplasia of the islands of Langerhans, and can lead to persistent hyperinsulinemic hypoglycemia. If appropriate treatment is delayed there is a high risk of the development of cerebral palsy, impaired mental development, epilepsy or other forms of irreversible brain damage, so early detection and early treatment to stabilize serum glucose levels is essential. Initial treatment consists of nutritional management with administration of an adequate amount of calories along with drug therapy using diazoxide. In cases that are resistant to drug therapy a subtotal pancreatectomy is performed. Conventional recommended practice has been to perform a 95% pancreatectomy, however this can lead to the onset of diabetes due to abnormal pancreatic endocrine function. We report here a case of nesidioblastosis in which we performed an 85% pancreatectomy. Postoperative clinical course has been excellent, with no recurrence or impaired glucose tolerance during the four years since the operation.

Clinical significance of plasma diamine oxidase activity in pediatric patients: influence of nutritional therapy and chemotherapy.

The aims of this study were to determine the normal values of plasma diamine oxidase (pDAO) activity in children and to examine the influence of several factors (nutritional management, dietary fiber, and chemotherapy) on pDAO activity. The activity of pDAO was measured in 138 healthy children with minor surgical conditions such as inguinal hernia or undescended testis. In order to define normal values patients were subdivided into 5 groups according to age. Next, changes in pDAO activity under different nutritional conditions were studied in 14 patients with adhesive ileus. The influence of chemotherapeutic drugs on pDAO activity was also studied in 19 neuroblastoma patients. I. The normal values of pDAO activity at year < 1, 1 < or = years < 3, 3 < or = years < 6.6 < or = years < 12, 12 < or = years were 6.65 +/- 1.75, 7.70 +/- 2.29, 6.53 +/- 1.68, 5.85 +/- 1.87, 5.06 +/- 1.84 units/l, respectively. II. The pDAO activities in patients with ileus were 4.73 +/- 1.02 (total parenteral nutrition), 6.84 +/- 1.18 (enteral, nutrition), 7.62 +/- 0.67 (soluble dietary fiber added enteral nutrition) and 8.82 +/- 1.26 units/l (oral feeding). The difference in pDAO activity at enteral or oral feeding vs. total parenteral nutrition was significant (p < .0001). III. The pDAO activity decreased significantly and remained low during the first 4 days after cyclophosphamide administration in neuroblastoma patients. The preadministration of dietary fiber inhibited the influence of cyclophosphamide. Plasma DAO activity was greatly influenced by nutritional management and administration of dietary fiber and/or cyclophosphamide. Plasma DAO activity may be a sensitive marker of intestinal function in children.