Complementary Indicators for Diagnosis of Hepatic Vein Stenosis After Pediatric Living-donor Liver Transplantation.

INTRODUCTION: Although hepatic vein stenosis after liver transplantation is a rare complication, the complication rate of 1% to 6% is higher in pediatric living-donor liver transplantation than that in other liver transplantation cases. Diagnosis is very important because this complication can cause hepatic congestion that develops to liver cirrhosis, graft loss, and patient loss. However, this is unlikely in cases where there are no ascites or hypoalbuminemia. OBJECTIVES: Eleven of 167 patients who had undergone pediatric living-donor liver transplantation were identified in the outpatient clinic at Jichi Medical University as having suffered from hepatic vein stenosis, and were enrolled in the study. METHODS: We conducted a retrospective study in which we reviewed historical patient records to investigate the parameters for diagnosis and examine treatment methods and outcomes. RESULTS: The 11 patients were treated with 16 episodes of balloon dilatation. Three among these received retransplantation and another 2 cases required the placement of a metallic stent at the stenosis. Histological examination revealed severe fibrosis in four of nine patients who had a liver biopsy, with mild fibrosis revealed in the other five grafts. Furthermore, hepatomegaly and splenomegaly diagnosed by computed tomography, elevated levels of hyarulonic acid, and/or a decrease in calcineurin inhibitor clearance were found to be pathognomonic at diagnosis, and tended to improve after treatment. CONCLUSIONS: Diagnosis of hepatic vein stenosis after liver transplantation can be difficult, so careful observation is crucial to avoid the risk of acute liver dysfunction. Comprehensive assessment using volumetry of the liver and spleen and monitoring of hyarulonic acid levels and/or calcineurin inhibitor clearance, in addition to some form of imaging examination, is important for diagnosis and evaluation of the effectiveness of therapy.

Abnormal asymmetries in subcortical brain volume in schizophrenia.

Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.

Iron overload after pediatric liver transplantation: a case report.

Iron is an essential nutrient for living cells; however, an excessive accumulation of iron leads to organ damage and directly affects systemic immunity. Iron overload is clinically classified as hereditary or secondary. Most of secondary iron overload is caused by frequent blood transfusions because there is no active mechanism to excrete iron from the body. As recommended in various guidelines, chelation therapy is effective for reducing iron burden and improving organ function. There have been few reports on iron overload through blood transfusion during the perioperative period of liver transplantation. This report presents a case of iron overload due to repeated transfusions after pediatric liver transplantation managed by chelation therapy. The patient, an 11-month-old female with biliary atresia, underwent living donor liver transplantation. She revealed refractory anemia and required frequent blood transfusion. Both serum ferritin and transferrin saturation tended to increase after repeated transfusions, leading to secondary iron overload. Iron chelation therapy was started to prevent progression to organ failure and infection due to iron overload, and yielded a favorable outcome. It is crucial to consider the possibility of secondary iron overload and to achieve early detection and treatment to avoid progression to irreversible organ damage.

Should isolated peritoneal carcinomatosis from colorectal cancer be sub-classified into stage IVB in era of modern chemotherapy?

BACKGROUND: According to the 7th edition of the TNM staging system, stage IV metastatic colorectal cancer (CRC) at the time of initial diagnosis is sub-classified into stage IVA or IVB disease. Peritoneal carcinomatosis (PC), considered to have a dismal prognosis, is exclusively sub-classified into stage IVB, even though other metastases to a sole organ are sub-classified into stage IVA, which is considered to be associated with better survival. This retrospective study was undertaken to investigate the overall survival in metastatic CRC patients, focusing on PC patients. METHODS: We reviewed data on patients with metastatic CRC at initial diagnosis surgically treated between January 2006 and June 2011. A survival analysis was performed paying special attention to PC and sub-classifying patients with PC into three categories according to metastatic sites. RESULTS: There were 69 stage IVA patients (IVA group) and 83 stage IVB. Among stage IVB patients, 20 had isolated PC (PC-I group), 28 had PC with one or more other sites of metastasis (PC-II group), and 35 had at least 2 metastatic without peritoneal involvement (NPC group). Of 152 stage IV patients, 132 (87 %) underwent resection of the primary tumor and 19 (12 %) underwent radical resection of metastatic disease with microscopic free margins (R0 resection) including 5/20 (25 %) patients in the PC1 group. A total of 139 patients received oxaliplatin-based chemotherapy in a palliative (n = 125), neoadjuvant (n = 3), or adjuvant setting after R0 resection (n = 11). Compared with 36.6 months in the PC-I group, median survival was 32.5 months (P = 0.48) in the IVA group, 14.7 months (P = 0.07) in the PC-II group, and 12.9 months (P < 0.01) in the NPC group. CONCLUSIONS: The sub-classification of isolated PC into stage IVA instead of IVB might be more appropriate in the era of modern chemotherapy. Further investigation is warranted.

Effect of local anesthesia on trigeminal somatosensory-evoked magnetic fields.

For objective neurophysiological evaluation of the function of the trigeminal system, magnetoencephalography- based TSEF (trigeminal somatosensory-evoked field) assessment would be valuable in providing spatial and temporal profiles of cortical responses. However, this necessitates knowledge of how TSEF varies with trigeminal nerve dysfunctions. We introduced a conduction block of the trigeminal nerve using local anesthesia (lidocaine) to temporally mimic nerve dysfunctions, and monitored TSEF changes. Following an electrical stimulation of the lower lip, a magnetic response with peak latency of approximately 20 ms was identified in all participants. Dipole for the peak was estimated on the post-central gyrus in the participant's own magnetic resonance image. After normalization to Montreal Neurological Institute (MNI) space and inter-participant data integration, the summary equivalent current dipole localization among participants remained in the post-central gyrus, suggesting validity of the use of MNI space. Partial anesthesia of the lower lip led to a loss of the waveform characteristics of TSEF for electrical stimulation to the trigeminal nerve. We verified that the 20-ms latency cortical response of TSEF components localized at the primary sensory cortex can serve as a robust neurofunctional marker of experimental trigeminal nerve dysfunction.

Decrease in tetrahydrobiopterin as a possible cause of nephropathy in type II diabetic rats.

A decrease in renal synthesis of nitric oxide (NO) in the progression of diabetic nephropathy has been documented. As (6R)-5,6,7,8-tetrahydrobiopterin (BH4) is an essential cofactor of NO synthase, we investigated whether BH4 deficiency is involved in the pathogenesis of nephropathy. Ten-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were used as a type II diabetic model, and Long-Evans Tokushima Otsuka (LETO) rats as the healthy controls. OLETF rats were orally treated with BH4 (10 mg/kg daily) or with water from 10 to 61 weeks of age. In another experiment, OLETF rats were treated orally with a calcium channel blocker, benidipine (5 mg/kg daily), or with 0.3% carboxymethyl cellulose (nontreated) from 10 to 52 weeks of age. Proteinuria was observed periodically, and at the end of the study, BH4 level and GTP cyclohydrolase I (GTPCH) activity in the kidney were measured. Proteinuria was observed at 13 weeks of age in the OLETF rats, and deteriorated until 61 weeks of age. Supplemental BH4 reduced the proteinuria. At 52 weeks of age, GTPCH activity and the BH4 level were decreased in the plasma and kidneys of OLETF rats, whereas they were significantly higher in the benidipine group than in the nontreated group. Proteinuria was milder in the benidipine group than in the nontreated group, without a concomitant decrease in blood pressure. Histologically observed glomerulosclerosis was mild in the BH4 and benidipine groups. In type II diabetic rats, renal BH4 is considered to play a crucial role in the pathogenesis of diabetic nephropathy. Benidipine was found to preserve BH4 levels, suggesting therapeutic renoprotective effects.

Neuropeptide Y overexpression in the preweanling Zucker (fa/fa) rat.

Hypothalamic preproNPY overexpression in the Zucker fatty (fa/fa) rat was examined. In situ hybridization was used to determine the relative level of preproNPY mRNA in the arcuate nucleus of +/+, +/fa, and fa/fa pups aged postnatal day 2 (P2), 5, 9, 12, or 25. The relative optical density (ROD) of probe hybridization in the arcuate, the area of hybridization (A), and the product of ROD x A (a measure of total arcuate preproNPY mRNA hybridization) were measured. Values were normalized to the mean +/fa value within each litter. Initial analysis showed that preproNPY mRNA hybridization (ROD x A) in fa/fa pups was significantly higher than +/fa and +/+ pups on P9, 12, and 25, and significantly higher than +/fa on P5. No significant difference between lean (+/+ and +/fa) genotypes, however, were observed at any age tested. Values from the lean genotypes were, therefore, pooled, and data were normalized to the mean value of lean animals for analysis. This analysis revealed that preproNPY mRNA hybridization in fa/fa pups was higher than lean littermates as early as P2.

Functional electrical stimulation for detrusor instability.

The clinical efficacy of functional electrical stimulation (FES) for female detrusor instability (DI) is reviewed. Various types of FES methods (including anogenital long-term stimulation, short-term maximal stimulation, implantable stimulation and transcutaneous stimulation) have been reported. The therapeutic effects of these approaches were similar: the percentage of patients improved has been reported to be in the range 50%-90%. FES for female DI is a non-destructive procedure with a curative effect and very few side effects. This curative effect (re-education) is a major benefit of FES.

Ontogeny of neuropeptide Y expression in response to deprivation in lean Zucker rat pups.

Hypothalamic neuropeptide Y (NPY) activity is believed to play an important role in the response to food deprivation in adult rats. Little is known, however, about the role of the hypothalamic NPY system in the control of food intake in the preweanling rat. To address this issue, we examined the effect of deprivation on arcuate nucleus preproNPY expression in lean Zucker rat pups, using in situ hybridization. PreproNPY expression within the arcuate nucleus was localized to cells in the medial portion. Twenty-four hours of food, water, and maternal deprivation significantly increased the relative abundance of preproNPY mRNA in pups on postnatal day (P) 2, P9, P12, and P15 by 14-31%. This response, however, was not observed on P5. The absence of an effect on P5 and the magnitude of the response at the other ages tested were not correlated with the amount of weight lost during deprivation.

Transcutaneous electrical stimulation of thigh muscles in the treatment of detrusor overactivity.

OBJECTIVE: To investigate the clinical effects on detrusor overactivity of a new method of transcutaneous reciprocal electrical stimulation of the thigh muscles. PATIENTS AND METHODS: Nineteen patients with detrusor overactivity, comprising 14 with detrusor hyperreflexia (DH) and five with idiopathic detrusor instability (IDI), were studied. Electrical stimulation was applied alternately to the quadriceps and hamstring muscles of one or both legs through surface electrodes for 20 min. The treatment was given once a day for 14 days and then the patients were evaluated urodynamically. RESULTS: All 19 patients tolerated the therapy well and none reported any adverse effects. The mean maximum cystometric capacity increased significantly (P < 0.05) after treatment. In 11 of the 19 patients, the maximum cystometric capacity was increased by > 50% of the pretreatment value; this occurred in eight of 14 of those with DH and in three of five of those with IDI. In six of the 11 who responded in this way, there was a clinical improvement in their urinary incontinence and frequency for several weeks to 3 months after the period of therapy. A second 14-day treatment was also effective in all four patients who underwent a repeat trial. CONCLUSION: This method of transcutaneous electrical stimulation can inhibit DH as well as IDI with no adverse effects. The suppressive effect on detrusor overactivity may persist for several months and repeat trials appear to be effective. Thus, we believe that this new stimulation technique should be tried as an alternative to other types of electrical stimulation and augmentation cystoplasty.

Protective effect of glycoprotein gC-rich antigen against pseudorabies virus.

A trial vaccine containing pseudorabies virus (PRV) glycoprotein gC as the main component showed excellent protection against virulent virus infection in pigs. Glycoprotein gC-rich antigen was prepared by heparin affinity chromatography from PRV-infected cell lysates. The preparations were mixed with mineral oil adjuvant as a water-in-oil emulsion. Six-week-old pigs were immunized twice at two-week intervals with trial vaccines containing 128,000, 12,800 and 1,280 HA units per dose of gC antigen. They were then challenged with a virulent PRV at day 7 after the final immunization. Neutralizing (NT) antibodies were produced with increase of antibody titers after challenge. Pigs immunized with 128,000 HA units per dose of gC survived and showed no virus shedding during the 2-week experimental period after the challenge. The role of cell-mediated immunity was examined using BALB/c mice, and induction of gC-specific cytotoxic T lymphocytes (CTLs) was detected by 51Cr release assay. From these results with mice, it is inferred that cell-mediated immunity, especially CTL, may play an important role in the effectiveness of our trial vaccine in addition to humoral immunity.

Steroidal glycosides from the fresh stem of Stephanotis lutchuensis var. japonica (Asclepiadaceae). Chemical structures of stephanosides K-Q.

The structural elucidation of seven related oxypregnane-oligoglycosides stephanosides K (1), L (2), M (3), N (4), O (5), P (6), and Q (7) from the fresh stem of Stephanotis lutchuensis var. japonica (Asclepiadaceae) was achieved through on a detailed study of their high-field 1H- and 13C-NMR spectra. The results show that all the sugars are beta (1-->4)-linked. The aglycones of stephanosides K, M, and O, and stephanosides L, N, and P were identified as 12-O-cinnamoyl-20-O-(E)-2-methyl-2-butenoyl, and 12-O-cinnamoyl-20-O-nicotinoyl derivatives of (20S)-pregn-6-ene-3 beta,5 alpha,8 beta,12 beta,14 beta,17 beta,20-heptaol, respectively. The aglycone of stephanoside Q was 12-O-cinnamoyldeacetylmetaplexigenin (kidjoranin).

Evaluation of angiogenic inhibitors with an in vivo quantitative angiogenesis method using agarose microencapsulation and mouse hemoglobin enzyme-linked immunosorbent assay.

In the present work, using a previously reported in vivo quantitative tumor-angiogenesis model, we attempted to ascertain whether this animal model is suitable for practical use in monitoring inhibitors of tumor angiogenesis. Mouse sarcoma-180 cells, human A431 cells or rat C6 cells microencapsulated in agarose beads were implanted s.c. into C57BL/6 mice. The level of blood vessel induction at the agarose pellet site was evaluated using mouse hemoglobin enzyme-linked immunosorbent assay on day 10 after implantation. Hydrocortisone, tetrahydro-S, medroxyprogesterone acetate, pentosan polysulfate and suramin inhibited blood vessel growth in our in vivo tumor-angiogenesis assay system, and heparin enhanced the antiangiogenic effects of hydrocortisone and tetrahydro-S. These results are almost entirely consistent with those observed in common assay systems, and suggest that this method may be useful for the identification and quantitative evaluation of inhibitors of tumor angiogenesis.

Effects of 17 beta-oestradiol and 5 alpha-dihydrotestosterone on the expression of the muscle and heart types of lactate dehydrogenase isozymes in the masseter muscle of developing mice.

17 beta-oestradiol (E2) and/or 5 alpha-dihydrotestosterone (5 alpha-DHT) had no effect on the expression of isozymes of lactate dehydrogenase (LDH) in the masseter muscle of intact male mice. However, treatment with E2 restored the level of the muscle (M) type of LDH isozyme, which had been reduced by testectomy, to that found in intact male mice treated with vehicle only. Moreover, 5 alpha-DHT alone was more effective than E2 in increasing the relative level of this isozyme in testectomized mice. 5 alpha-DHT had a more significant effect on the increase in the relative level of the M-type LDH isozyme when combined with E2. These results suggest that androgens promote, in the presence of oestrogens, the postnatal changes in the characteristics of the masseter muscle of developing male animals.

Intracellular Ca2+ dynamics and in vitro secretory response in acute pancreatitis induced by a choline-deficient, ethionine-supplemented diet in mice.

In order to approach impaired stimulus-secretion coupling in acute pancreatitis induced by a choline-deficient, ethionine-supplemented (CDE) diet in mice, the agonist-evoked intracellular Ca2+ dynamics of dispersed pancreatic acini were evaluated by microspectrofluorometry. Mice were fed a CDE diet for 24 or 48 h, and the pancreas was dispersed to the acini. The in vitro amylase secretion analysis of the CDE groups demonstrated a poor dose-response curve which was significantly lower (p < 0.01) when 100 pM cholecystokinin (CCK) was administered. Both in CDE and control groups, the application of a physiological dose of CCK-8 (10 pM) evoked intracellular Ca2+ oscillations. Periodicity and amplitude of the oscillations in the CDE groups were not significantly different. The administration of a higher dose of CCK-8 (100 pM) evoked a large, sharp, and transient rise in intracellular Ca2+, followed by a small, continuous increase above basal levels for the duration of stimulation both in CDE and control groups. The peak Ca2+ level was lower in the CDE groups, but this was not statistically significant. In conclusion, during the early phase (from 24 to 48 h) of CDE pancreatitis, the pattern of agonist-evoked intracellular Ca2+ release is less affected. Other mechanisms subsequent to the onset of intracellular Ca2+ release are likely to be involved in the inhibition of enzyme secretion.

[The study of Chinese herbal medicinal prescription with enzyme inhibitory activity. VI. The study of makyo-kanseki-to with adenosine 3',5'-cyclic monophosphate phosphodiesterase].

A Chinese herbal medicinal prescription, Makyo-kanseki-to, was studied for the inhibitory activity of adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase. The effect for the inhibitory activity of cAMP phosphodiesterase by combination with constituent crude drugs of the prescription was studied. Gypsum acted as a mitigatory component for Ephedra herb and Glycyrrhiza in cAMP phosphodiesterase inhibition test.

Pharmacological action of hachimijiogan (Ba-wei-wan) on the metabolism of aged subjects.

In order to elucidate the active mechanism of traditional Chinese medicine, we investigated the effects of Hachimijiogan which has been alleged to restore the function of old degenerated organs. After administering Hachimijiogan to aged rats and mice, we examined the lipid and glutathione metabolism. The cholesterol and triglyceride levels in the mice liver were significantly decreased in the Hachimijiogan treated group. The cholesterol turnover was examined using labeled cholesterol in aged mice, and Hachimijiogan may increase the turnover of cholesterol metabolism. The lenticular glutathione levels and enzyme activities concerned with glutathione metabolism were investigated in aged rats given Hachimijiogan, suggesting that Hachimijiogan may offer protective and therapeutic effects against senile cataract. From our study, Hachimijiogan is considered to improve the lipid and glutathione metabolism as a result of its complicated in vivo compound effects.

Antitumor activities and tumor necrosis factor producibility of traditional Chinese medicines and crude drugs.

The antitumor activities and capacity for tumor necrosis factor (TNF) production of traditional Chinese herbal preparations (Zhu-ling-tang, Xiao-chai-hu-tang), crude drugs (Polyporus, Hoelen, Bupleuri radix, Angelica radix, Cnidii rhizoma, Cinnamomum cortex), and Krestin (PSK) were investigated. These drugs were given to DDY mice in the drinking water before and after transplantation of Ehrlich tumors, and the development of the intradermally transplanted Ehrlich tumors and survival rate were observed. A good survival rate and sometimes a complete cure were found in the groups administered Bupleuri radix, Xiao-chai-hu-tang, Angelica radix, or Cinnamomum cortex, while the group given Hoelen showed poor results. To examine the capacity for TNF production these drugs were given to DDY mice PO as initial stimulating agents, to stimulate the reticuloendothelial system (RES) prior to lipopolysaccharide injection. The TNF activity was tested from the cytotoxicity against L cells. Significant differences in capacity for TNF production were observed among the drugs. Relatively high levels of TNF activity were noted in the groups given Angelica radix, Bupleuri radix, Cnidii rhizoma, or Cinnamomum cortex, very low activities in the groups given Xiao-chai-hu-tang, Zhu-ling-tang, or Krestin, and no TNF activities in the groups given Polyporus or Hoelen. The TNF capacity for production broadly paralleled the survival rate of the mice transplanted to Ehrlich tumors. Our findings suggest that one mechanism underlying the antitumor activities of these drugs is based on stimulation of the RES and is closely related of TNF production.