Is there a clinical difference in paediatric congenital cholesteatoma according to age?

OBJECTIVE: This study aimed to analyse surgical outcomes of paediatric patients with congenital cholesteatoma according to age. METHOD: This was a retrospective study reviewing the records of 186 children (136 boys and 50 girls) from August 1993 to January 2016. Patients were divided into three age groups (equal to or less than 3 years, over 3 and less than 7 years, and 7 to 15 years). RESULTS: There were significant differences in chief complaints, location of cholesteatoma in the middle ear, computed tomography findings, operation methods, ossicular erosion and type of cholesteatoma sac among the three groups. In addition, older age, open type cholesteatoma, ossicular erosion and mastoid invasion of cholesteatoma increased the recurrence rate after surgery. However, despite higher pre-operative air-bone gap in older children, hearing can be improved enough after proper surgery with ossicular reconstruction. CONCLUSION: Delayed detection of paediatric cholesteatoma can lead to extensive disease and the need for an aggressive operation, which can result in worse hearing outcomes and an increased recurrence risk.

Background model for the NaI(Tl) crystals in COSINE-100.

The COSINE-100 dark matter search experiment is an array of NaI(Tl) crystal detectors located in the Yangyang Underground Laboratory (Y2L). To understand measured backgrounds in the NaI(Tl) crystals we have performed Monte Carlo simulations using the Geant4 toolkit and developed background models for each crystal that consider contributions from both internal and external sources, including cosmogenic nuclides. The background models are based on comparisons of measurement data with Monte Carlo simulations that are guided by a campaign of material assays and are used to evaluate backgrounds and identify their sources. The average background level for the six crystals (70 kg total mass) that are studied is 3.5 counts/day/keV/kg in the (2-6) keV energy interval. The dominant contributors in this energy region are found to be 210 Pb and 3 H.

Warfarin therapy and perioperative transfusion requirement with bleeding amount in patients undergoing cardiac surgery with cardiopulmonary bypass: a retrospective study.

OBJECTIVES: The study was designed to evaluate the effect of warfarin on perioperative transfusion, bleeding and coagulation status in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). BACKGROUND: There were controversy about the effect of warfarin on perioperative transfusion and bleeding. METHODS/MATERIALS: Medical records from 107 consecutive patients with atrial fibrillation (AF) on warfarin therapy undergoing cardiac surgery with cardiopulmonary bypass (CPB) from 2008 to 2013 at a single university teaching hospital were retrospectively reviewed to compare the patients on to those not on warfarin therapy in terms of perioperative transfusion requirement, postoperative 24-h bleeding amount, and coagulation status assessment using prothrombin time (PT), international normalised ratio (INR) and rotational thromboelastometry (ROTEM®). RESULTS: Although PT/INR was significantly prolonged both before and after surgery in patients on warfarin therapy, ROTEM® data, perioperative transfusion requirement and postoperative 24-h bleeding amount (785 ± 331 vs 676 ± 303 mL, P = 0·089, respectively) were not significantly different between the patients on and those not on warfarin therapy. CONCLUSION: In patients on warfarin therapy undergoing cardiac surgery with CPB, warfarin therapy did not significantly increase perioperative transfusion requirement and bleeding.

A macrophage-specific synthetic promoter for therapeutic application of adiponectin.

Foam cell formation from macrophage is a major cause of atherosclerosis. An efficient macrophage-specific promoter is required for the targeting to macrophages. In this study, we develop a macrophage-specific synthetic promoter for the therapeutic application of adiponectin (APN), an antiatherogenic gene. Synthetic promoter-146 (SP146), registered on the NCBI website (http://www.ncbi.nlm.nih.gov/nuccore/DQ107383), was tested for promoter activities in two non-macrophage cell lines (293 T, HeLa) and a macrophage cell line (RAW264.7, bone marrow-derived macrophages). To enforce macrophage specificity, partial elements of p47(phox) including the PU.1 site with various lengths (-C1, -C2 and -C3) were inserted next to the synthetic promoters. SP146-C1 showed the highest specificity and efficacy in RAW264.7 cells and was selected for development of an APN-carrying macrophage-specific promoter. Green fluorescent protein (GFP)- or APN-expressing lentivirus under SP146-C1 (Lenti-SP-GFP or Lenti-SP-APN, respectively) showed the highest expression efficacy in RAW264.7 cells compared with the non-macrophage cell lines. APN overexpression in RAW264.7 cells successfully inhibited intracellular lipid accumulation, and atherosclerotic lesions and lipid accumulation were significantly reduced by Lenti-SP-APN in ApoE-/- atherosclerosis mice. In conclusion, the synthetic promoter SP146-C1, combined with a p47(phox) promoter element, was successfully developed to target macrophage, and macrophage-specific introduction of APN under SP146-C1 was shown to ameliorate the atherosclerotic pathology.

Long thoracic nerve block in video-assisted thoracoscopic wedge resection for pneumothorax.

We hypothesised that relaxation of the serratus anterior muscle by long thoracic nerve (LTN) block could help pain relief after video-assisted thoracoscopic surgery. Patients undergoing thoracoscopic wedge resection for pneumothorax were randomly assigned to control or LTN block. LTN block was performed before induction of general anaesthesia. Pain was evaluated using a visual analogue scale before anaesthesia induction (T0), on arrival to the post-anaesthetic care unit (PACU) (T1), every ten minutes after arrival in the PACU for 30 minutes (T2, T3 and T4) and one hour and 24 hours after discharge from the PACU (T5 and T6). Visual analogue scale scores from T1 to T5 in the block group were lower than the control group (T1: 36±11 vs 48±14 [P=0001], T2: 36±11 vs 51±15 [P<0.001], T3: 35±vs 52±15 [P<0.001], T4: 30±7 vs 45±17 [P<0.001] and T5: 26±5 vs 32±5 [P<0.001]). Total intravenous patient-controlled analgesia bolus dose (alfentanil 75 µg/ml) during PACU stay (1.6±1.2 vs 3.9±2.0 ml, P<0.001) and one hour after discharge from the PACU (0.5±0.8 vs 1.7±1.2 ml, P<0.001) in the LTN group was significantly lower than the control group. Total intravenous patient-controlled analgesia bolus dose from 1-24 hours after discharge from the PACU was similar between groups (P=0197). These findings indicate that LTN block reduced pain after video-assisted thoracoscopic surgery from end-of-surgery to one hour after discharge from the PACU.

Noninvasive cardiac output monitoring in paediatric cardiac surgery: correlation between change in thoracic fluid content and change in patient body weight.

OBJECTIVE: Change in thoracic fluid content (TFC) derived via a bioreactance technique with a noninvasive cardiac output monitoring device (NICOM) reportedly shows a good correlation with the amount of fluid removed. The present study prospectively evaluated the utility and clinical application of TFC in the intraoperative fluid management of paediatric patients with congenital heart disease, undergoing cardiac surgery with bioreactance-based noninvasive monitoring. METHODS: Haemodynamic parameters, patient body weight and parameters derived from the NICOM device (including cardiac output, cardiac index, TFC, percentage change in TFC compared with baseline [TFCd0%] and stroke volume variation) were recorded after anaesthesia induction but before surgical incision, and just before departure from the operating room to the intensive care unit. RESULTS: In the 80 paediatric patients included in this study, linear regression analyses demonstrated good correlations between body weight gain and TFCd0%, between body weight gain % and TFCd0%, and between intra operative fluid balance and TFCd0%. CONCLUSION: TFCd0% may be a useful indicator for intraoperative fluid management in paediatric patients with congenital heart disease, undergoing cardiac surgery.

Does near-infrared spectroscopy provide an early warning of low haematocrit following the initiation of hypothermic cardiopulmonary bypass in cardiac surgery?

This study investigated 151 patients undergoing cardiac surgery to determine whether measurement of regional cerebral oxygen saturation (rS(c)O(2)) using near-infrared spectroscopy (NIRS) can indicate a low haematocrit after initiation of hypothermic cardiopulmonary bypass (CPB). Haematocrit, rS(c)O(2), haemoglobin level, arterial partial pressures of carbon dioxide and oxygen, systemic blood pressure, and nasopharyngeal and rectal temperatures were determined 5 min after the initial administration of heparin for CPB and 90 s after completion of the first cardioplegic solution injection. Immediately after initiation of hypothermic CPB, rS(c)O(2), haemoglobin and haematocrit values were significantly lower than those before CPB. No significant correlations were found between the change in haematocrit and changes in left, right and mean rS(c)O(2); thus, changes in rS(c)O(2) before and after initiation of hypothermic CPB did not reflect changes in haematocrit values. This indicates that NIRS cannot provide early warning of a low haematocrit immediately after initiation of hypothermic CPB in cardiac surgery.

The effect of ulinastatin on postoperative blood loss in patients undergoing open heart surgery with cardiopulmonary bypass.

This prospective, randomized, double-blind study evaluated the effect of ulinastatin on postoperative blood loss and transfusion requirements of patients undergoing open-heart surgery with cardiopulmonary bypass (CPB) and aortic cross-clamping (ACC). CPB and ACC produce variable systemic inflammatory reactions that are associated with multiorgan dysfunction via leucocytes, especially polymorphonuclear neutrophils (PMNs). PMNs increase blood loss and transfusion requirements. Ulinastatin, a urinary trypsin inhibitor, inhibits PMN activity and reduces the systemic inflammatory response. Patients received either 5000 U/kg ulinastatin or the equivalent volume of normal saline (control group) before ACC. Postoperative blood loss and transfusion requirements were recorded. Duration of intubation and length of stay in the intensive care unit (ICU) were also noted. There were no statistically significant between-group differences in postoperative blood loss and transfusion requirements. Ulinastatin caused a non-significant decrease in duration of intubation. Patients who received ulinastatin had significantly shorter ICU stays than control patients.

In vitro effects of ulinastatin on blood coagulation using thromboelastography.

AIM: The effects of ulinastatin, urinary trypsin inhibitor, on coagulation are not fully understood. The aim of the present study was to examine the in vitro effects of ulinastatin on coagulation using modified computerised thromboelastography (ROTEM®) with InTEM®. METHODS: A venous blood sample was obtained from the antecubital vein without stasis from 12 healthy adult men. A 290 µL aliquot of blood was combined with either 10 µL of ulinastatin (100 [U100], 200 [U200] or 1000 [U1000] U/mL) or 10 µL of normal saline. The samples were analysed simultaneously at 37 ºC on a four channel ROTEM® with InTEM®. RESULTS: Clotting time was significantly increased in the U200 (155.8±9.3 s) and U 1000 (173.6±14.5 s) groups, compared with the control group (136.1±12.6 s). The U 1000 group significantly increased clot formation time (77.6±16.2 s; control group, 63.8±13.4 s) and significantly decreased α angle (74.6±3.3º; control group, 77.4±2.4º). No significant difference in maximum clot firmness or maximum lysis was found between the control and ulinastatin groups. CONCLUSION: In-vitro ulinastatin had a direct anticoagulant effects, as assessed by ROTEM® with InTEM®, and the results were within the normal ranges.

Clinical and sonographic parameters at 37 weeks' gestation for predicting the risk of primary Cesarean delivery in nulliparous women.

OBJECTIVES: To identify the clinical and sonographic parameters at 37 weeks' gestation that predict the risk of Cesarean delivery in labor for nulliparas. METHODS: This prospective observational study recruited nulliparas with singleton pregnancies at 37 weeks' gestation. Determination of the Bishop score, ultrasound measurement of the cervical length, and fetal biometry were performed. The clinical parameters studied were maternal age, height and weight and Bishop score. The sonographic parameters included fetal biparietal diameter, femur length, abdominal circumference (AC), estimated fetal weight (EFW), amniotic fluid index and cervical length. RESULTS: Four hundred and fifty-three women were examined; 57 women (12.6%) underwent an emergency Cesarean delivery in labor. Logistic regression analysis identified maternal age and height and fetal AC and EFW, but not cervical length or Bishop score, as the best predictors of Cesarean delivery. Of these predictors, maternal age and height and fetal AC at 37 weeks were included in a final model for risk scoring. The model was shown to have an adequate goodness of fit (P = 0.473), and the area under the receiver-operating characteristics curve was 0.758, indicating reasonably good discrimination. CONCLUSIONS: Maternal age and height and fetal AC and EFW at 37 weeks' gestation are the most important parameters in predicting the risk of Cesarean delivery in nulliparas; sonographic measurement of the cervical length and the Bishop score were not predictive of Cesarean delivery. A predictive model using these parameters at 37 weeks provides useful information in the decision-making process regarding the mode of delivery.

Degree of cervical shortening after initial induction of labor as a predictor of subsequent successful induction.

OBJECTIVE: To evaluate whether the degree of cervical length shortening is valuable in predicting the success of serial induction of labor on the second day in women in whom it failed on the first day, and to compare its performance with that of cervical length. METHODS: This was a prospective observational study. We enrolled 92 consecutive women with singleton gestations at > 34.0 weeks' gestation who failed labor induction on the first day of serial induction. Transvaginal sonographic measurement of cervical length and determination of the Bishop score were undertaken before performing each labor induction on the first and second days. RESULTS: The overall success rate of labor induction performed on the second day was 65% (60/92). Multiple logistic regression analysis demonstrated that the degree of cervical length shortening and cervical length were significantly associated with the successful induction of labor after adjustment for body mass index, parity, use of prostaglandin and Bishop score. There were no significant differences between areas under the ROC curves for degree of cervical length shortening and cervical length. CONCLUSIONS: The degree of cervical length shortening is valuable in predicting the success of induction of labor on the second day in women in whom induction failed on the first day. However, compared with sonographic cervical length it is no better at predicting the success of subsequent induction of labor.

Superfine saengshik improves liver protecting effect compared with fine saengshik in an animal model.

This study was performed to compare the effect of liver protection of fine saengshik (FS) and superfine saengshik (SS) and uncooked and powdered grains and vegetables, produced by the different mill technique on the acute hepatotoxicity induced by CCl(4) in mouse. As the result of particle size distribution in number, particles included under 0.955 microm dia were 7.02% and 68.92% respectively. Hematological and serological examination showed that AST (P < 0.05) and ALT (P < 0.05) of SS + CCl(4) group decreased significantly compared with those of FS + CCl(4) group. On the examination of antioxidant effect, water extract of SS showed a higher superoxide dismutase (SOD)-like activity on the condition of the HX/XOD system than that of FS (P < 0.001). Also, the glutathione peroxidase (P < 0.01) and glutathione reductase (P < 0.05) activities in liver showed a significant difference between FS + CCl(4) and SS + CCl(4) groups. On the histological observation of liver, SS + CCl(4) group showed a mild reversible hepatocytic change and infiltration of inflammatory cells around the central veins, whereas FS + CCl(4) group showed severe agglutination necrosis by CCl(4) toxicity. These results suggest that superfine saengshik significantly improves liver protection effect compared with fine saengshik; its major mechanism is supposed to be the improved antioxidant effect of saengshik by reduced size of particles.

Light- and electron-microscopic analysis of neuropeptide Y-immunoreactive amacrine cells in the guinea pig retina.

We investigated the morphology and synaptic connections of neuropeptide Y (NPY)-containing neurons in the guinea pig retina by immunocytochemistry, using antisera against NPY. Specific NPY immunoreactivity was localized to a population of wide-field and regularly spaced amacrine cells with processes ramifying mainly in stratum 1 of the inner plexiform layer (IPL). Double-label immunohistochemistry demonstrated that all NPY-immunoreactive cells possessed glutamic acid decarboxylase 65 immunoreactivity. The synaptic connectivity of NPY-immunoreactive amacrine cells was identified in the IPL by electron microscopy. The NPY-labeled amacrine cell processes received synaptic input from other amacrine cell processes and bipolar cell axon terminals in stratum 1 of the IPL. The most frequent postsynaptic targets of NPY-immunoreactive amacrine cells were other amacrine cell processes. Synaptic outputs to bipolar cells were also observed in a small number of cases. This finding suggests that NPY-containing amacrine cells may influence inner retinal circuitry in stratum 1 of the IPL, thus mediating visual processing.

Antiplatelet activity of green tea catechins is mediated by inhibition of cytoplasmic calcium increase.

We have previously reported that green tea catechins (GTC) display a potent antithrombotic activity, which might be due to antiplatelet rather than anticoagulation effects. In the current study, we investigated the antiplatelet mechanism of GTC. We tested the effects of GTC on the aggregation of human platelets and on the binding of fluorescein isothiocyanate-conjugated fibrinogen to human platelet glycoprotein (GP) IIb/IIIa. GTC inhibited the collagen-, thrombin-, adenosine diphosphate (ADP)-, and calcium ionophore A23187-induced aggregation of washed human platelets, with 50% inhibitory concentration values of 0.64, 0.52, 0.63, and 0.45 mg/ml, respectively. GTC significantly inhibited fibrinogen binding to human platelet surface GPIIb/IIIa complex but failed to inhibit binding to purified GPIIb/IIIa complex. These results indicate that the antiplatelet activity of GTC may be due to inhibition of an intracellular pathway preceding GPIIb/IIIa complex exposure. We also investigated the effects of GTC on intracellular calcium levels, which are critical in determining the activation status of platelets and on induction of platelet aggregation by thapsigargin, which is a selective inhibitor of the Ca(2+)-ATPase pump. Pretreatment of human platelets with GTC significantly inhibited the rise in intracellular Ca(2+) concentration induced by thrombin treatment, and GTC significantly inhibited the thapsigargin-induced platelet aggregation. We also examined the effect of GTC on the second messenger, inositol 1,4,5-triphosphate (IP(3)). GTC significantly inhibited the phosphoinositide breakdown induced by thrombin. Taken together, these observations suggest that the antiplatelet activity of GTC is be mediated by inhibition of cytoplasmic calcium increase, which leads to the inhibition of fibrinogen-GPIIb/IIIa binding via the activation of Ca(2+)-ATPase and inhibition of IP(3) formation.

The expression and cellular localization of phospholipase D1 in the rodent retina.

Phospholipase D (PLD) is one of the intracellular signal transduction enzymes and plays an important role in a variety of cellular functions. We investigated the expression and cellular localization of the PLD isozyme PLD1 in the rodent retina. Western blot analysis showed the presence of PLD1 at the protein level in the rat, mouse and guinea pig retinas. PLD1 immunoreactivity was localized in all Müller cells. Thus, PLD1 protein appears to be important in the functions of these cells in the rodent retina.

Somatodendritic localization of Translin, a component of the Translin/Trax RNA binding complex.

Recent studies implicating dendritic protein synthesis in synaptic plasticity have focused attention on identifying components of the molecular machinery involved in processing dendritic RNA. Although Translin was originally identified as a protein capable of binding single-stranded DNA, subsequent studies have demonstrated that it also binds RNA in vitro. Because previous studies indicated that Translin-containing RNA/single-stranded DNA binding complexes are highly enriched in brain, we and others have proposed that it may be involved in dendritic RNA processing. To assess this possibility, we have conducted studies aimed at defining the localization of Translin and its partner protein, Trax, in brain. In situ hybridization studies demonstrated that both Translin and Trax are expressed in neurons with prominent staining apparent in cerebellar Purkinje cells and neuronal layers of the hippocampus. Subcellular fractionation studies demonstrated that both Translin and Trax are highly enriched in the cytoplasmic fraction compared with nuclear extracts. Furthermore, immunohistochemical studies with Translin antibodies revealed prominent staining in Purkinje neuron cell bodies that extends into proximal and distal dendrites. A similar pattern of somatodendritic localization was observed in hippocampal and neocortical pyramidal neurons. These findings demonstrate that Translin is expressed in neuronal dendrites and therefore support the hypothesis that the Translin/Trax complex may be involved in dendritic RNA processing.

Antithrombotic and antiplatelet activities of 2-chloro-3-[4-(ethylcarboxy)-phenyl]-amino-1,4-naphthoquinone (NQ12), a newly synthesized 1,4-naphthoquinone derivative.

The possibility of NQ12 (2-chloro-3-[4-(ethylcarboxy)-phenyl]-amino-1,4-naphthoquinone) as a novel antithrombotic agent and its mode of action were investigated. The effects of NQ12 on platelet aggregation in human platelet-rich plasma in vitro, in rats ex vivo, and on murine pulmonary thrombosis in vivo, as well as the mode of antithrombotic action were examined. NQ12 potently inhibited ADP-, collagen-, epinephrine-, and calcium ionophore-induced human platelet aggregations in vitro concentration-dependently. NQ12 significantly inhibited rat platelet aggregation in an ex vivo study. NQ12 prevented murine pulmonary thrombosis in a dose-dependent manner. However, NQ12 did not affect coagulation parameters such as activated partial thromboplastin time, prothrombin time, and thrombin time. NQ12 inhibited fibrinogen binding to the platelet surface GPIIb/IIIa receptor, but failed to inhibit binding to the purified GPIIb/IIIa receptor. Thromboxane B(2) formation caused by thrombin or collagen was inhibited significantly by NQ12. The phosphoinositide breakdown induced by thrombin or collagen was inhibited concentration-dependently by NQ12. These results suggest that NQ12 may be a promising antithrombotic agent, and its antithrombotic activity may be due to antiplatelet aggregation activity, which may result from the inhibition of phosphoinositide breakdown and thromboxane A(2) formation.

Cellular distribution of isozymes of protein kinase C in septal olfactory epithelium of mice.

To determine the presence of protein kinase C (PKC) isozymes in the septal olfactory epithelium of mice (mSOE), western blotting and immunohistochemistry were performed using antibodies against PKC isozymes. With the exception of PKC-betaI, all of the PKC isozymes were detected in the whole lysate of septal tissue layer and apparent molecular weights for each isoform were found. PKC-alpha, PKC-gamma and PKC-epsilon were detected in the olfactory glandular cells of the lamina propria, and PKC-betaI and PKC-betaII were located in the microvillar cells. Neither novel PKC nor atypical PKC was detected in olfactory glandular cells or microvillar cells, except for PKC-epsilon. PKC-lambda was localized in the mucous layer of the mSOE. Meanwhile, PKC-delta and PKC-xi were distributed in the receptor cells in the mSOE. These data demonstrate the isoform-specific expression of PKC in mSOE and suggest a role for the novel and atypical types of PKC in olfactory transduction.

Studies on the antithrombotic and antiplatelet activities of NQ304, a newly synthesized naphthoquinone derivative.

The effect of p6304 (2-chloro-3-(4-hexylphenyl)-amino-1,4-naphthoquinone) as a novel antithrombotic agent was investigated. NQ304 was found to inhibit platelet aggregation in human platelets in vitro and in rat ex vivo, and murine pulmonary thrombosis in vivo. NQ304 potently inhibited adenosine diphosphate (ADP), collagen, epinephrine and calcium ionophore-induced human platelet aggregation in vitro dose-dependently. In the ex vivo study, oral administration of NQ304 significantly inhibited platelet aggregation in rats. However, NQ304 was found not to affect the coagulation system, since it did not change the prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT). The agent prevented death due to pulmonary thrombosis by the platelet aggregates in mice in vivo. In the mouse tail bleeding time test, NQ304 showed a significant prolongation of the tail bleeding time in conscious mice. These results suggest that a principal antithrombotic effect of NQ304 may be due to the antiplatelet aggregation activity but not to anticoagulation activity.