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Background: Because the thoracic esophageal carcinoma has a high metastatic rate to the upper mediastinal lymph nodes, especially along the recurrent laryngeal nerves (RLN), it is crucial to perform a complete lymphadenectomy along the RLN without complications. Although intraoperative neural monitoring (IONM) during thyroid surgery has gained widespread acceptance as a useful tool for visual nerve identification, utilization of IONM during esophageal surgery has not become common. Here, we describe our procedures, focusing on a lymphadenectomy along the RLN utilizing the IONM.Methods: Eighty-seven patients who underwent prone esophagectomy between December 2009 and September 2017 were included in this study. We divided patients into two groups: neural monitoring group (Nm, n = 31) and conventional method group without IONM (Cm, n = 56). We first dissect around the esophagus, preserving the membranous structure; mesoesophagus, which contains tracheoesophageal artery; RLN; and lymph nodes (mesenterization). In Nm group, we next identify the location of the RLN, which runs in the mesoesophagus using IONM before visual contact. Next, we perform lymphadenectomy around the RLN, preserving the nerve itself. Early surgical outcomes were retrospectively compared between two groups.Results: In all 31 cases in the Nm group, we detected the location of the RLN before the visual contact. The sensitivity and specificity of the IONM to detect the RLN paralysis were 67% and 96%, respectively. Postoperative RLN paralysis was observed in 3 cases in the Nm group (9.7%), which was lower than that in the Cm group (32.1%, p = 0.03). Clavien-Dindo grade 2 and over aspiration were seen in 2 (Nm, 6.5%) and 16 (Cm, 28.6%) cases (p = 0.01), respectively. The postoperative hospital stay was shorter in the Nm group (22 days, median) than in the Cm group (39 days, median, p = 0.0002). The number of dissected mediastinal lymph nodes was similar in both groups (25 vs. 20, median, p = 0.12).Conclusions: The combination of IONM and the concept of the mesoesophagus have substantial advantages in allowing accurate and safe mediastinal lymphadenectomy during prone esophagectomy. [ABSTRACT FROM AUTHOR]

Anti-thymocyte globulin (ATG) is a key drug in immunosuppressive therapy for patients with aplastic anemia. The mainstay of ATG therapy had been a horse ATG (hATG) formulation, Lymphoglobulin or ATGAM, but Lymphoglobulin was recently discontinued, and Thymoglobulin, a rabbit ATG (rATG) formulation, is currently used as the first-line drug in many countries, including Japan. However, a recent randomized clinical trial reported significantly unfavorable outcomes associated with the use of rATG regimens. We retrospectively analyzed clinical outcomes of adult patients with moderate to severe aplastic anemia who were treated with 3.5 mg/kg of Thymoglobulin (n = 22) or 15 mg/kg of Lymphoglobulin (n = 25) in our facility. The estimated overall response rates in the rATG and hATG groups were 64.6 versus 56.0 % at 6 months, and 76.4 versus 69.2 % at 12 months, respectively; and there was no statistical difference between the two groups (P = 0.32). Overall survival at 24 months was not significantly different: rATG 89.8 % versus hATG 96.0 % (P = 0.39). Early phase infection was observed in 37.5 % of cases in the rATG and 14.8 % in the hATG group, but the frequency was not statistically different (P = 0.107). Our data indicate that Thymoglobulin at a dose of 3.5 mg/kg is a viable alternative when hATG is not available. [ABSTRACT FROM AUTHOR]

Background: Patients with hypoalbuminemia often fail to respond to increased doses of loop diuretics. We therefore performed a post hoc analysis to investigate the pharmacological action of tolvaptan and whether it is dependent on the serum albumin level.Methods: This analysis was based on four previous clinical trials of tolvaptan in patients with liver cirrhosis who exhibited insufficient response to conventional diuretics. We analyzed the correlation between the change in the initial 24-h cumulative urine volume from baseline and the serum albumin level at baseline, and assessed potential predictive factors of response to tolvaptan.Results: The correlation coefficient was 0.029 in the placebo group and -0.112 in the 7.5 mg tolvaptan group of patients with liver cirrhosis. Administration of tolvaptan provoked a stable response regardless of the serum albumin level. Tolvaptan use was identified as a significant predictor of pharmacological action, and was shown to change the initial urine volume by 885 mL (P < 0.0001) in liver cirrhosis patients.Conclusions: In this post hoc analysis, tolvaptan increased the initial urine volume from baseline regardless of serum albumin levels. Use of tolvaptan as an add-on therapy to loop diuretics can be considered an optimal therapeutic option in patients with insufficient response to loop diuretics. [ABSTRACT FROM AUTHOR]

Neurodevelopmental and neurodegenerative theories may be viewed as incompatible accounts that compete to explain the pathogenesis of schizophrenia. However, it is possible that neurodevelopmental and neurodegenerative processes could both reflect common underlying causal mechanisms. We hypothesized that cognitive dysfunction would gradually deteriorate over time in schizophrenia and the degree of this deterioration in adulthood would be predicted by an infant measure of neurodevelopment. We aimed to examine the association between age of learning to stand in infancy and deterioration of cognitive function in adulthood. Participants were nonpsychotic control subjects (n = 76) and participants with schizophrenia (n = 36) drawn from the Northern Finland 1966 Birth Cohort study. The schizophrenia group showed greater deterioration in abstraction with memory than controls, but there were no differences between schizophrenia and controls in rate of change of other cognitive measures. Age of learning to stand in infancy significantly inversely predicted later deterioration of abstraction with memory in adult schizophrenia (later infant development linked to greater subsequent cognitive deterioration during adulthood), possibly suggesting a link between abnormal neurodevelopmental and neurodegenerative processes in schizophrenia. [ABSTRACT FROM PUBLISHER]

Background and Purpose: We previously reported that pre-ischaemic i.v. miglitol reduces myocardial infarct size through the inhibition of glycogenolysis during ischaemia. Oral administration of miglitol has been reported to produce glucagon-like peptide 1 (GLP-1). We hypothesized that p.o. administration of miglitol, an absorbable antidiabetic drug, reduces myocardial infarct size by stimulating GLP-1 receptors and inhibiting glycogenolysis in the myocardium.Experimental Approach: The effects of p.o. and i.v. administration of miglitol on myocardial infarct size were compared in a rabbit model of ischaemia induced by 30 min of coronary occlusion and 48 h of reperfusion. The levels of phospho(p)-PI3kinase and p-Akt were measured in cardiac tissue by use of Western blot analysis.Results: Both p.o. and i.v. administration of miglitol reduced the infarct size, and this effect was greater after p.o. than after i.v. administration under similar plasma miglitol concentrations. The reduction in infarct size induced by p.o. miglitol but not that induced by i.v. miglitol was partially inhibited by treatment with exendin(9-39), a GLP-1 receptor blocker. Both p.o. and i.v. miglitol improved ejection fraction and ±dP/dt after myocardial infarction. Miglitol administered p.o. but not i.v. up-regulated the myocardial expression of phospho(p)-PI3kinase and p-Akt following myocardial infarction; an effect that was inhibited by exendin(9-39).Conclusions and Implications: Administration of miglitol p.o. reduces myocardial infarct size through stimulation of GLP-1 receptors and activation of PI3kinase-Akt pathway in addition to the inhibition of glycogenolysis. These findings may have clinical implications for the p.o. administration of miglitol for the treatment of patients with diabetes mellitus combined with coronary artery disease. [ABSTRACT FROM AUTHOR]

This study was undertaken to compare magnetic resonance angiography (MRA) and gastrointestinal tract endoscopy (ENDO) for detecting varices in postoperative biliary atresia (BA) patients. Thirty-four BA patients were divided into groups according to age and liver function; group 1: 1-4 years old; group 2: 5-9 years old; group 3: over 10 years old; group A: normal liver function; and group B: moderate liver dysfunction. All subjects had MRA and ENDO. ENDO showed esophageal or gastric varices in 16 of 34 subjects. MRA depicted gastroesophageal vessels in 12 of 16 cases with varices on ENDO (sensitivity: 75%). Two subjects appeared to have varices on MRA that could not be confirmed on ENDO. Sixteen subjects had no varices on ENDO and normal MRA (specificity: 88.9%). Sensitivities and specificities of MRA for detecting varices were 20 (1/5) and 100% (6/6) in group 1 (n = 11), 100 (6/6) and 66.7% (4/6) in group 2 (n = 12), 100 (5/5) and 100% (6/6) in group 3 (n = 11), 100 (8/8) and 100% (9/9) in group A (n = 17), 50 (4/8) and 77.8% (7/9) in group B (n = 17), respectively. From these findings, MRA was not accurate in BA patients less than 10 years old or with moderate liver dysfunction. Therefore, periodic endoscopic examination is recommended for the accurate assessment and follow-up of varices in postoperative BA patients. [ABSTRACT FROM AUTHOR]

The oriental herbal formulation inchin-ko-to (ICKT) inhibits liver cell apoptosis induced by transforming growth factor-beta 1 (TGF-beta1). This study evaluated the effect of ICKT on serum markers of liver function and liver fibrosis in postoperative biliary atresia (BA) patients. Twenty-one postoperative BA patients with elevated GOT, GPT and gamma-GTP, but normal serum total bilirubin levels, were divided into two groups arbitrarily; an ICKT group (n = 12), and a no-ICKT group (n = 9). Serum markers of liver function [GOT, GPT, gamma-GTP, total bile acids (TBA)], and serum markers of liver fibrosis [hyaluronic acid (HA), type IV collagen (C-IV)], were measured in both groups at the beginning of the study, and at 1, and 3 years after the beginning of the study and the results compared statistically. All patients tolerated ICKT well, and there were no side effects. In the ICKT group, mean serum HA levels were significantly decreased at 1 year (P < 0.012), and at 3 years, both mean serum HA and C-IV were significantly decreased (P < 0.001 and P < 0.003, respectively). However, mean serum levels of GOT, GPT, gamma-GTP, and TBA did not change significantly following ICKT use for any length of time (all P > 0.05). Administration of ICKT in postoperative BA patients appears to lower the serum levels of markers of fibrosis in the medium-term. Whether this in fact correlates with prevention cannot be determined from this paper, but ICKT would appear to protect against liver fibrosis. Long-term studies are required to determine the exact role ICKT plays in prognosis of BA patients. [ABSTRACT FROM AUTHOR]

Connective tissue growth factor (CTGF) is a newly described protein that stimulates transforming growth factor-beta1 (TGF-beta1). We evaluated the expression of CTGF mRNA in operative biopsy specimens from biliary atresia (BA) patients and normal controls to assess the role of CTGF in BA. Liver biopsy specimens were taken from BA patients at the time of portoenterostomy (n=22) and compared with specimens taken from normal controls (n=6). In situ hybridization was used to stain CTGF mRNA in all specimens. The distribution of collagen type IV (C-IV) was also assessed in the same specimens as an indicator of the severity of fibrosis present at the time of biopsy. Results were analyzed to determine whether there was any correlation between CTGF and C-IV and outcome. Of the 22 postoperative BA patients, eventual outcome was good in 17 (group I), and five (group II) subsequently required liver transplantation. Control specimens (n=6) had no apparent CTGF mRNA expression, and median C-IV positive immunoreactivity was 1.23+/-0.25%. CTGF mRNA was weakly expressed in hepatic stellate cells (HSC) and hepatocytes in specimens from group I, and median C-IV-positive immunoreactivity was 3.18+/-0.86%. However, in specimens from group II, there was increased CTGF mRNA in HSC and hepatocytes. Median C-IV-positive immunoreactivity was 6.31+/-0.96%. There was a significant correlation between CTGF mRNA intensity and the amount of C-IV, which implies that CTGF expression reflects prognosis. This study provides the first evidence that CTGF is strongly expressed in BA, in particular in HSC and hepatocytes, suggesting that they may be a source of CTGF. The strong correlation with C-IV indicates that CTGF plays a major role in the pathogenesis of progressive fibrosis in BA. [ABSTRACT FROM AUTHOR]

Cathelicidins are a family of antibacterial peptides. Human cathelicidin LL-37 inhibits the binding of endotoxin lipopolysaccharide (LPS) to CD14-positive cells and could ameliorate sepsis. The aim of this study was to observe the effect of LL-37 on sepsis in neonatal rats. Intraperitoneal injection (IPI) of LPS was used to create sepsis in suckling rats. Group 1 rats were given LPS with LL-37, group 2 rats were given LL-37 2 h after LPS, and group 3 rats were given LPS without LL-37. Control group rats were given isovolemic normal saline by IPI. Rats given LL-37 IPI were divided into seven subgroups. Following IPI, an overall assessment score (OAS) and rectal temperature (RT) were assessed hourly. Serum C-reactive protein (CRP) was also assessed at death or at sacrifice 10 h after IPI. All rats in group 3 died. For rats receiving lower doses of LL-37 in groups 1 and 2, mortality was decreased. No deaths occurred among those receiving higher doses of LL-37 in group 1; however, mortality increased in group 2. In group 1, OAS and RT deteriorated initially for those receiving lower doses of LL-37, then improved. OAS and RT did not deteriorate throughout the study in rats given higher doses of LL-37. In group 2 rats given higher doses of LL-37, OAS and RT were not significantly different from rats in group 3. CRP was significantly decreased in group 1 compared with group 3, and decreased in group 2 for lower doses only. We conclude that LL-37 may prevent sepsis and be useful in lower doses for treating sepsis. However, LL-37 appears to have adverse effects when used at higher doses for treating sepsis. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine circulating levels of adhesion molecules in serum from patients with congenital diaphragmatic hernia (CDH) to investigate the relationship between soluble ICAM-1, ELAM-1, and VCAM-1 liberated by activated vascular endothelium and the development of persistent pulmonary hypertension (PPH) in patients with CDH. We measured serum levels of ICAM-1, ELAM-1, and VCAM-1 in 20 high-risk neonates with CDH at the time of diagnosis (11 with PPH and 9 without PPH) and 7 age-matched controls using ELISA system. We further examined the lungs of 5 patients with CDH complicated by PPH who died during resuscitation and stabilization, and three control lung specimens for the expression of adhesion molecules using immunohistochemistry. The mean serum ICAM-1 levels in CDH patients with PPH (227.0+/-98.9 ng/ml) were increased compared with levels in CDH patients without PPH (140.29+/-37.4 ng/ml; p<0.05) and controls (130.0+/-23.8 ng/ml; p<0.05). Mean serum ELAM-1 levels in CDH patients with PPH (116.5+/-19.2 ng/ml) were significantly increased compared with levels in CDH patients without PPH (79.3+/-27.9 ng/ml; p<0.01) and controls (58.4+/-14.5 ng/ml; p<0.001). Mean serum VCAM-1 levels in CDH patients with PPH (1596.9+/-460.4 ng/ml) were significantly higher compared with levels in CDH patients without PPH (1069.3+/-444.6 ng/ml; p<0.01) and controls (838.0+/-171.2 ng/ml; p<0.001). But serum adhesion molecule levels in CDH patients without PPH were no different from controls statistically. Pulmonary vascular endothelial cells from CDH lung with PPH had strong expression of adhesion molecules compared with controls. Up-regulated expression of adhesion molecules on the endothelium of pulmonary vessels and high circulating levels of adhesion molecules in CDH patients with PPH suggest that adhesion molecules may play a role in the development of PPH in CDH. [ABSTRACT FROM AUTHOR]

To study the surgical treatment and outcome of hydronephrosis secondary to pelviureteric junction obstruction (PUJS) that is so massive that the renal pelvis crosses over the vertebral column [mega-hydronephrosis (MH)]. Of the 40 cases of PUJS we treated over the past 5 years, 6 cases had MH secondary to PUJS (MH-PUJS) in 6 renal units and were reviewed. Incidence of MH was 15.0%. All had Anderson-Hynes dismembered pyeloplasty to treat obstructive renal pattern on technetium-99m diethylenetriaminepentaacetic acid (DTPA) scans in five and gait disturbance due to MH in one. The contralateral kidney was normal in five and dysplastic in one. Three had nephrostomy before pyeloplasty. Preoperative DTPA scans showed good renal function in four and poor in two. Plication of the entire dilated, lax renal parenchyma ("nephroplication") was performed in three to decrease the intra-renal pelvic cavity. Prenatal diagnosis was performed in three cases. Mean age at pyeloplasty was 3.5 years and mean duration of follow-up was 1.5 years. Postoperatively, two of the three who did not have nephroplication had prolonged but not obstructed renal pattern on DTPA scans, and the other case who did not have nephroplication had nephrectomy for non-functioning kidney caused by recurrent pyelonephritis 2 years after pyeloplasty. In the three who had nephroplication, DTPA scans showed acceptable to relatively good passage in all cases. The surgical treatment of MH-PUJS is challenging with no fixed guidelines. However, nephroplication may be useful during pyeloplasty to decrease the size of MH-PUJS. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Shakuyakukanzoto (SKT) composed of Glycyrrhizae radix (G. radix) and Paeoniae radix (P. radix) has been traditionally used in Japan, Korea and China as an antispasmodic drug for the treatment of skeletal muscle cramps and intestinal cramps. Aim of this study: To evaluate the antispasmodic activity of SKT and its two components, as well as to identify the key constituents of the components which mediate this effect in skeletal muscles in vivo. Materials and methods: An experimental cramp model was constructed to evaluate the effects of peripherally-acting muscle relaxants on electrically-induced cramps under physiological conditions. This was accomplished by surgically isolating the motor supply to the gastrocnemius muscle in an anesthetized rat and delivering electrical stimuli to an isolated tibial nerve to induce tetanic contractions. We first tested dantrolene, a well-known peripherally-acting relaxant, to determine the sensitivity and reliability of our experimental model. We then evaluated the effects of SKT, P. radix, G. radix, and the eight active constituents of G. radix against tetanic contractions. Results: We found that dantrolene (10 and 30mg/kg, i.d.) rapidly and significantly inhibited tetanic contractions (P<0.01) irrespective of dose. SKT (0.5, 1.0, and 2.0g/kg, i.d.) and G. radix (0.5 and 1.0g/kg, i.d.) also significantly inhibited tetanic contractions (P<0.01) but in a dose-dependent manner owing to the actions of six of the eight active constituents in G. radix (liquiritin apioside, liquiritigenin, isoliquiritin apioside, isoliquiritigenin, glycycoumarin, and glycyrrhetinic acid, 20μmol/kg, i.v.). These constituents, which include flavonoids, a triterpenoid, and a courmarin derivative, demonstrated temporal variations in their inhibitory activity. In contrast, P. radix (0.5 and 1.0g/kg, i.d.) did not show a statistically significant antispasmodic effect in our study; however, we previously found that it had a significant antinociceptive effect. Conclusions: Our findings show that SKT inhibits tetanic contractions in vivo and that G. radix is the main antispasmodic component due to the actions of its active constituents, thus supporting the traditional use of SKT. We further propose that SKT containing the antispasmodic G. radix and antinociceptive P. radix is a pharmaceutically elegant option for muscle cramps as treatment requires a two-pronged approach, i.e., inhibition of hyperexcitable skeletal tissues and modulation of the pain accompanying cramps. [Copyright &y& Elsevier]