[Basic and Advanced Techniques of Anastomosis in Deep Surgical Fields:STA-SCA Anastomosis].

This article detailly describes the subtemporal-transtentorial STA-SCA bypass technique. Through temporal base drilling, copious cerebrospinal fluid evacuation before retraction, and sufficient retraction of the temporal lobe preserving the veins of the temporal base would be primodial to obtain an appropriate surgical field. Refrection of the tentrial free edge and identification of recipient SCA posterior to the entry point of the trochlear nerve into the cavernous sinus is a micro-anatomical key. Bilateral bayonet-type needle holders and forceps should be used not to shadow the surgical corridor with one's hands.

Molecular Identification of UDP-Sugar-Dependent Glycosyltransferase and Acyltransferase Involved in the Phenylethanoid Glycoside Biosynthesis Induced by Methyl Jasmonate in Sesamum indicum L.

Sesame (Sesamum indicum L.) plants contain large amounts of acteoside, a typical phenylethanoid glycoside (PhG) that exhibits various pharmacological activities. Although there is increasing interest in the biosynthesis of PhGs for improved production, the pathway remains to be clarified. In this study, we established sesame-cultured cells and performed transcriptome analysis of methyl jasmonate (MeJA)-treated cultured cells to identify enzyme genes responsible for glucosylation and acylation in acteoside biosynthesis. Among the genes annotated as UDP-sugar-dependent glycosyltransferase (UGT) and acyltransferase (AT), 34 genes and one gene, respectively, were upregulated by MeJA in accordance with acteoside accumulation. Based on a phylogenetic analysis, five UGT genes (SiUGT1-5) and one AT gene (SiAT1) were selected as candidate genes involved in acteoside biosynthesis. Additionally, two AT genes (SiAT2-3) were selected based on sequence identity. Enzyme assays using recombinant SiUGT proteins revealed that SiUGT1, namely, UGT85AF10, had the highest glucosyltransferase activity among the five candidates against hydroxytyrosol to produce hydroxytyrosol 1-O-glucoside. SiUGT1 also exhibited glucosyltransferase activity against tyrosol to produce salidroside (tyrosol 1-O-glucoside). SiUGT2, namely, UGT85AF11, had similar activity against hydroxytyrosol and tyrosol. Enzyme assay using the recombinant SiATs indicated that SiAT1 and SiAT2 had activity transferring the caffeoyl group to hydroxytyrosol 1-O-glucoside and salidroside (tyrosol 1-O-glucoside) but not to decaffeoyl-acteoside. The caffeoyl group was attached mainly at the 4-position of glucose of hydroxytyrosol 1-O-glucoside, followed by attachment at the 6-position and the 3-position of glucose. Based on our results, we propose an acteoside biosynthetic pathway induced by MeJA treatment in sesame.

Traumatic pseudoaneurysm resulting from avulsion of the falcine branch of an azygos anterior cerebral artery: a case report.

Traumatic anterior cerebral artery (ACA) aneurysms are extremely rare. Traumatic anterior ACA aneurysms are thought to develop when the ACA at the pericallosal segment travel adjacent to immobile falx cerebri. As the majority of aneurysms are pseudoaneurysms, direct neck clipping is usually not possible, and it is often necessary to carry out direct or endovascular trapping in conjunction with proficient bypass techniques. The authors describe the first reported case of a traumatic ACA pseudoaneurysm resulting from avulsion of the falcine branch of an azygos ACA. In this case, the lacerated aneurysm wall was successfully sutured, without the need for a bypass. Neurosurgeons should be aware that avulsion of the falcine branch arising from the ACA can occur, and that this may cause a traumatic aneurysm on the distal ACA. Furthermore, direct suturing of a lacerated arterial wall should be considered a treatment option for this type of traumatic intracranial aneurysm.

Determination of Mogroside V in Luohanguo Extract for Daily Quality Control Operation Using Relative Molar Sensitivity to Single-Reference Caffeine.

Mogroside V is one of the characteristic and effective components of luohanguo extract, a food additive used as a sweetener in Japan as per Japan's Standards and Specifications for Food Additives (JSFA; 9th ed.). JSFA stipulates that the quantitative determination for mogroside V content in luohanguo extract applies HPLC using analytical standard mogroside V. However, no mogroside V reagents with proven purities are commercially available. Therefore the current JSFA determination method is not particularly suited for daily quality control operations involving luohanguo extract. In this study, we applied an alternative quantitative method using a single reference with relative molar sensitivity (RMS). It was possible to calculate the accurate RMS by an offline combination of 1H-quantitative NMR spectroscopy (1H-qNMR) and an HPLC/variable-wavelength detector (VWD). Using the RMS of mogroside V to a commercial certified reference material grade caffeine, the mogroside V contents in luohanguo extracts could be determined using HPLC/VWD without analytical standard mogroside V. There was no significant difference between the mogroside V contents in luohanguo extracts determined using the method employing single-reference caffeine with the RMS and using the JSFA method. The absolute calibration curve for the latter was prepared using an analytical standard mogroside V whose purity was determined by 1H-qNMR. These results demonstrate that our proposed method using a single reference with RMS is suitable for quantitative determination of mogroside V in luohanguo extract and can be used as an alternative method to the current assay method in JSFA.

Acquired isolated hypoganglionosis as a distinct entity: results from a nationwide survey.

PURPOSE: Acquired isolated hypoganglionosis (A-IH) is a late-onset intestinal pseudo-obstruction disorder and shows different pathophysiological findings from congenital isolated hypoganglionosis (C-IH). In this study, we retrospectively examined five cases of A-IH and investigated the features of A-IH. METHODS: Five cases of A-IH were extracted from a nationwide retrospective cohort study in 10 years, from which totally 355 cases of Allied Disorders of Hirschsprung's Disease (ADHD) were collected. RESULTS: Ages of onset were between 13 and 17 years in three cases, and 4 years and 4 months in ones. Initial symptoms were abdominal distension and/or chronic constipation in 4 cases, whereas one exhibited intestinal perforation. Affected lesions varied from case to case, extending various length of intestinal tracts. All cases underwent multiple operations (average: 4.6 times), such as enterostomy, resection of dilated intestines, and/or pull-through. Pathological findings showed the decreased numbers of ganglion cells and degeneration of ganglion cells, whereas the size of the plexus was normal. Currently, all cases were alive and almost all eat regular food without requiring parenteral feeding. CONCLUSION: A-IH is rare, but distinct entity characterized by different clinical courses and pathological findings from those of C-IH. The outcome is considered to be favorable after a resection of affected intestine.

Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease, 2017.

BACKGROUND: Despite the presence of ganglion cells in the rectum, some patients have symptoms similar to those of Hirschsprung's disease. A consensus has yet to be established regarding the terminology for these diseases. We defined this group of diseases as "allied disorders of Hirschsprung's disease" and compiled these guidelines to facilitate accurate clinician diagnosis and provide appropriate treatment strategies for each disease. METHODS: These guidelines were developed using the methodologies in the Medical Information Network Distribution System (MINDS). Of seven allied disorders, isolated hypoganglionosis; megacystis-microcolon-intestinal hypoperistalsis syndrome; and chronic idiopathic intestinal pseudo-obstruction were selected as targets of clinical questions (CQ). In a comprehensive search of the Japanese- and English-language articles in PubMed and Ichu-Shi Web, 836 pieces of evidence related to the CQ were extracted from 288 articles; these pieces of evidence were summarized in an evidence table. RESULTS: We herein outline the newly established Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease. Given that the target diseases are rare and intractable, most evidence was drawn from case reports and case series. In the CQ, the diagnosis, medication, nutritional support, surgical therapy, and prognosis for each disease are given. We emphasize the importance of full-thickness intestinal biopsy specimens for the histopathological evaluation of enteric ganglia. Considering the practicality of the guidelines, the recommendations for each CQ were created with protracted discussions among specialists. CONCLUSIONS: Clinical practice recommendations for allied disorders of Hirschprung's disease are given for each CQ, along with an assessment of the current evidence. We hope that the information will be helpful in daily practice and future studies.

Pharmacotherapy for pediatric chronic intestinal pseudo-obstruction: Nationwide survey in Japan.

BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) is a rare disabling and life-threatening disorder characterized by severe impairment of gastrointestinal peristalsis. While a number of pharmacotherapeutics have been developed, only a few trials have been carried out for improvement of the pathological condition of CIPO patients. This report describes the results of a nationwide survey on the pharmacotherapy used in pediatric CIPO in Japan. METHODS: In 2012, a nationwide survey was conducted to identify the clinical presentation of CIPO in Japan. Information was gathered on pharmacotherapy. Four categories were created for medicines used in pharmacotherapy: "probiotics", "Japanese herbal medicines (Kampo medicines)", "laxatives", and "prokinetics". RESULTS: Ninety-two responses were collected from 47 facilities. Of the 62 patients who met the diagnostic criteria, 52 were treated with medications, while the remaining 10 were not. Thirty-four patients were given a total of 49 probiotics; 39 were treated with a total of 50 Kampo medicines; 20 were treated with a total of 28 laxatives; and 26 were given a total of 30 prokinetics, 70% of whom were treated specifically with mosapride. CONCLUSION: Traditional Japanese medicines such as Kampo medicines and mosapride are often used to treat CIPO in Japan. Two combinations, that is, probiotics and Kampo medicines; and Kampo medicines and prokinetics, were often used for pediatric CIPO in Japan.

The novel preventive effect of Daikenchuto (TJ-100), a Japanese herbal drug, against neonatal necrotizing enterocolitis in rats.

PURPOSE: Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of premature infants. Daikenchuto, a Japanese herbal drug, has several effects on the digestive system, so we investigated its preventive effects in a rat model of NEC. METHODS: NEC was induced in newborn rats via asphyxia (100% N2 for 90 s; every 4 h) + LPS (4 mg/kg/day [administered orally on days 0 and 1]). The effects of Daikenchuto were evaluated in four groups (control: 0 g/kg/day, I: 0.3 g/kg/day, II: 0.6 g/kg/day, and III: 1.0 g/kg/day). Daikenchuto was administered into the stomach through a microcatheter. The incidence and severity of NEC were pathologically assessed using the NEC grade in accordance with Dovorak's previous report. Cell positivity for inflammatory cytokine (IL-6) was also evaluated. RESULTS: Daikenchuto reduced the incidence of NEC in control, Groups I, II, and III to 68.7, 30.0, 30.7, and 13.3%, respectively. High-dose Daikenchuto significantly improved the incidence of NEC, and the rate of IL-6 positive cells in group III was significantly lower than in the control group (p = 0.04). CONCLUSION: We evaluated the effect of Daikenchuto against NEC and found that it reduced the incidence rate of NEC due to a decrease in the IL-6 production.

Identification of a novel variant of the RET proto-oncogene in a novel family with Hirschsprung's disease.

PURPOSE: Hirschsprung's disease (HSCR) is a congenital disorder of the enteric nervous system characterized by the absence of ganglion cells in the Auerbach's and Meissner's plexuses. Although about 7% of cases are hereditary, the causal mutations have not been completely characterized. We encountered a novel family with inherited HSCR and screened them for causal mutations. METHODS: A Japanese family of five female patients and six unaffected individuals was subjected to a whole-exome analysis with a next-generation sequencer. RESULTS: After exome sequencing and the annotation of mutations, we identified co-segregated mutations with sequential filtering steps via a standard protocol. Eight mutations were identified: two on chromosome 10 and six on chromosome 11. We used pathogenicity prediction tools such as Genomic Evolutionary Rate Profiling, SIFT, and PolyPhen2 to predict the impact of mutations on the protein activity. S922Y, a novel mutation of RET, was identified as a likely causal mutation. In addition, a mutation of rs2435357T, known as enhancer of RET located in intron 1 of RET, was detected in this family. CONCLUSION: The coexistence of RET mutations in both the exon (S922Y) and intron1 (rs2435357T) indicated a risk of HSCR in this family.

[A Case of Slowly Progressive Brain Metastasis with Minor Bleeding after Removal of and Chemotherapy for Non-Small Cell Lung Cancer].

Of all brain metastases, the most common primary lesion is derived from the lung. These types of metastases enlarge aggressively with unfavorable prognoses. We report the case of a 75-year-old male patient who had a history of pulmonary resection for Stage IA non-small cell lung cancer(NSCLC), and received chemotherapy. One year after NSCLC surgery, he experienced a cardiogenic cerebral infarction, and anticoagulant therapy was initiated. Mass lesions with hemorrhage were detected bilaterally in the frontal lobes through magnetic resonance imaging three years after the NSCLC surgery. The lesions slowly enlarged during follow-up. However, there were no clinical symptoms. There was no finding indicating a local recurrence or metastasis through positron emission tomography(PET). Two and a half years after the detection of the lesion, left hemiplegia was observed. Massive hemorrhage from the right frontal lobe lesion was observed on computed tomography(CT). Craniotomy and evacuation of the hematoma were performed. The histopathological findings showed adenocarcinoma and the diagnosis was brain metastasis of the lung cancer. This case reveals brain metastasis of lung cancer that progressed without extracranial metastases for three years. The brain tumor enlarged, accompanied by hemorrhage, extremely slowly without any symptoms. It was difficult to differentiate between metastasis and cavernous hemangioma, considering the extremely slow progress and image analyses. Of the reported prognostic factors associated with postoperative brain metastasis from surgically resected NSCLC, three factors were applicable to this case:adenocarcinoma, a small number of brain metastases, and the absence of extracranial metastases at the diagnosis of brain metastasis. We should consider the possibility of a metastatic brain tumor secondary to lung cancer even long after thoracic surgery.

Identification of New Diterpenes as Putative Marker Compounds Distinguishing Agnus Castus Fruit (Chaste Tree) from Shrub Chaste Tree Fruit (Viticis Fructus).

Agnus Castus Fruit is defined in the European Pharmacopoeia as the dried ripe fruit of Vitex agnus-castus. In Europe it is used as a medicine targeting premenstrual syndrome and climacteric disorder. In Japan, Agnus Castus Fruit is becoming popular as a raw material for over-the-counter drugs and health food products, though its congenic species, Vitex rotundifolia and Vitex trifolia, have been used as Shrub Chaste Tree Fruit in traditional medicines. Therefore, it is important to discriminate these Vitex plants from the viewpoint of regulatory science. Here we tried to identify putative marker compounds that distinguish between Agnus Castus Fruit and Shrub Chaste Tree Fruit. We analyzed extracts of each crude drug by liquid chromatography-mass spectrometry, and performed differential analysis by comparison of each chromatogram to find one or more peaks characteristic of Agnus Castus Fruit. A peak was isolated and identified as an equilibrium mixture of new compounds named chastol (1) and epichastol (1a). The planar structures of 1 and 1a were determined spectroscopically. Their relative configurations were revealed by nuclear Overhauser effect spectroscopy and differential nuclear Overhauser effect-NMR data. Since avoiding contamination from closely related species is needed for the quality control of natural pharmaceuticals, this information will be valuable to establish a method for the quality control of both, Agnus Castus Fruit and Shrub Chaste Tree Fruit products.

Determination and Identification of a Specific Marker Compound for Discriminating Shrub Chaste Tree Fruit from Agnus Castus Fruit Based on LC/MS Metabolic Analysis.

Shrub Chaste Tree Fruit (SCTF) is defined as the fruits of Vitex rotundifolia L. f. and V. trifolia L. and has been used as a component of some traditional Japanese medicines (Kampo formulations). Agnus Castus Fruit (ACF) is defined as the dried ripe fruits of V. agnus-castus L.; it is used in traditional European medicines, but is becoming popular in Japan as both an over-the-counter drug and as an ingredient in health foods for treating premenstrual syndrome (PMS). To ensure the efficacy and safety of both SCTF and ACF products, it is important to precisely authenticate their botanical origins and to clearly distinguish between SCTF and ACF. Therefore, we tried to identify SCTF-specific marker compounds based on LC/MS metabolic analysis. The multivariate analysis of LC/MS data from SCTF and ACF samples furnished candidate marker compounds of SCTF. An SCTF-specific marker was isolated from SCTF crude drugs and identified as 3-O-trans-feruloyl tormentic acid on the basis of spectroscopic data from NMR and MS. Since avoiding contamination from closely related species is a significant requirement for pharmaceuticals of natural origin, this information will be valuable for the quality control of both SCTF and ACF products from the viewpoint of regulatory science.

[Current Management of Congenital Diaphragmatic Hernia].

Three types of congenital diaphragmatic hernias( Bochdalek hernia, Morgagni hernia, and esophageal hiatus hernia) are described with case presentation. In the Bochdalek hernia, the most common type of congenital diaphragmatic hernia, abdominal contents pass into the thorac bia diaphragmatic defect, limiting the space available for the developing lungs. Resulting lung hypoplasia, many infants experience severe respiratory distress within minutes of birth and may require resuscitation and stabilization of cardio-pulmonary function prior to surgery. The Morgagni hernia is rare and often incidentally diagnosed on routine chest x-ray in asymptomatic patients. Repair is still advisable due to risk of strangulated bowel and respiratory distress. Esophageal hiatal hernias usually produce symptoms of gastroesophageal reflux( GERD) and rarely result in incarceration of stomach or other organs. Surgical interventions for GERD, such as Nissen fundoplication, usually target neurologically impaired children in order to prevent aspiration pneumonia and improve quality of life. Laparoscopic surgery is beneficial for all types of diaphragmatic hernia, especially in older children, but careful consideration should be made based on individual patient background.

Measuring free, conjugated, and halogenated estrogens in secondary treated wastewater effluent.

Steroidal estrogens are potent endocrine-disrupting chemicals that enter natural waters through the discharge of treated and raw sewage. Because estrogens are detrimental to aquatic organisms at sub-nanogram per liter concentrations, many studies have measured so-called "free" estrogen concentrations in wastewater effluents, rivers, and lakes. Other forms of estrogens are also of potential concern because conjugated estrogens can be easily converted to potent free estrogens by bacteria in wastewater treatment plants and receiving waters and halogenated estrogens are likely produced during wastewater disinfection. However, to the best of our knowledge, no studies have concurrently characterized free, conjugated, and halogenated estrogens. We have developed a method that is capable of simultaneously quantifying free, conjugated, and halogenated estrogens in treated wastewater effluent, in which detection limits were 0.13-1.3 ng L(-1) (free), 0.11-1.0 ng L(-1) (conjugated), and 0.18-18 ng L(-1) (halogenated). An aqueous phase additive, ammonium fluoride, was used to increase the electrospray (negative mode) ionization efficiency of free and halogenated estrogens by factors of 20 and 2.6, respectively. The method was validated using treated effluent from the greater Boston metropolitan area, where conjugated and halogenated estrogens made up 60-70% of the steroidal estrogen load on a molar basis.

Application of nuclear medicine to achieve less invasive surgery for malignant solid tumors in children.

BACKGROUND: The use of nuclear medicine for the management of malignant tumor, such as radioguided surgery and sentinel lymph node biopsy (SLNB), has been widely accepted in the adult practice. However, there are very few studies to apply those techniques for pediatric diseases. The aim of this study was to investigate the feasibility of application of nuclear medicine in surgery for neuroblastoma (NB) or rhabdomyosarcoma (RMS) in children. METHODS: Radioguided surgery using (123) I-metaiodobenzylguanidine was performed on six children with NB. SLNB using technetium-labeled tin or sulfur colloid was performed on two children with perineal RMS. Histological evaluation of resected specimens was performed to determine the accuracy of intraoperative detection and SLNB. All patients were evaluated for overall survival and complications. RESULTS: Intraoperative tumor localization using hand-held gamma probe was helpful in 85.7% of NB patients. Sensitivity and specificity of this technique were 81.8% and 93.3%, respectively. There were no postoperative complications, and four out of five patients with high-risk NB experienced disease-free survival (median follow up, 57 months). Sentinel lymph nodes were easily detected in patients with perineal RMS, and histological assessment revealed complete consistency with regional lymph node status. CONCLUSIONS: Nuclear medicine may have a potential application in the use of less invasive surgery for advanced NB or perineal RMS, the two most challenging pediatric malignancies.

Development of an HPLC method using relative molar sensitivity for the measurement of blood concentrations of nine pharmaceutical compounds.

We developed a reliable high-performance liquid chromatographic analysis method using a relative molar sensitivity (RMS) technique that does not require an authentic, identical reference analyte material to quantify blood serum carbamazepine, phenytoin, voriconazole, lamotrigine, meropenem, mycophenolic acid, linezolid, vancomycin, and caffeine levels for routine blood concentration measurements. Carbamazepine and caffeine were also used as non-analyte reference materials to calculate the RMS of each analyte. The RMS was calculated from the ratio of the slope of the calibration equation (analyte/non-analyte reference material), then used to quantify analytes in control serum samples spiked with carbamazepine, phenytoin, voriconazole, meropenem, mycophenolic acid, linezolid or vancomycin. In addition, the concentrations of these six drugs in control serum samples determined by the proposed RMS method agreed well with that obtained using a conventional method. The proposed RMS method is a promising tool for the clinical determination of nine drugs, given the accuracy, precision, and efficiency of quantifying these analytes.

Report from the Committee for Improving the Work Environment of Japanese Surgeons: survey on effects of the fee revision for medical services provided by surgeons.

PURPOSE: The aim of this study was to achieve improvements in the work environment of Japanese surgeons and shortage of surgeons. METHODS: Questionnaires were distributed to selected Japanese surgical Society (JSS) members. Retrospective analysis was conducted comparing the current 2011 survey with previous 2007 survey. To examine the influence of 2010 revision of the fee for medical services performed by surgeons, we distributed a second questionnaire to directors of hospitals and administrators of clerks belonging to official institutes in JSS. Collective data were analyzed retrospectively. RESULTS: The main potential causes for the shortage of surgeons in Japan were long hours (72.8 %), excessive emergency surgeries (69.4 %), and high risk of lawsuit (67.7 %). Mean weekly working hours of surgeons in national or public university hospitals and private university hospitals were 96.2 and 85.6, respectively. Approximately 70 % of surgeons were forced to do hardworking tasks, possibly leading to death from overwork. Of note, approximately 25 % of surgeons had over time of more than 100 h a week, coinciding to the number of hours that might lead to death from fatigue, described in the Japanese labor law. Although the total medical service fee in hospitals, especially in large-scale hospitals with more than 500 beds, increased markedly after 2010 revision of the fee for medical services performed by surgeons, few hospitals gave perquisites and/or incentives to surgeons. CONCLUSION: To prevent and avoid collapse of the surgical specialty in Japan, an improvement in the work environment of surgeons by initiation of the JSS would be required as soon as possible.