STIM1 knock-down decreases the affinity of obinutuzumab for CD20 by altering CD20 localization to Triton-soluble membrane.

Obinutuzumab is thought to exert its effects through its high antibody-dependent cellular cytotoxicity (ADCC) via glyco-engineering of the Fc region. In addition, obinutuzumab causes direct binding-induced cell death (DCD) only by specifically binding to its target CD20, a Ca2+ channel. However, the specific features of CD20 related to obinutuzumab binding-induction of cell death are not clearly understood. In this study, we evaluated the relationship between the Ca2+ channel features of CD20 as a store-operated Ca2+ channel (SOC) and obinutuzumab binding-induced cell death. Ca2+ channel function and biochemical analysis revealed that CD20 is an Orai1- and stromal interaction molecule (STIM1)-dependent Ca2+ pore. However, binding of obinutuzumab on CD20 did not have any effect on Ca2+ influx activity of CD20; the direct cell death rate mediated by obinutuzumab binding was almost equivalent with or without the extracellular Ca2+ condition. Given the apparent interaction between STIM1 and CD20, we observed Triton-X solubilized obinutuzumab-bound CD20 accompanied by STIM1. Subsequently, obinutuzumab binding and cell death were decreased by STIM1 knock-down in Ramos B cells. Thus, STIM1 directly contributes to cell death by increasing the affinity of cells for obinutuzumab by transferring CD20 to the Triton-soluble membrane region.

Contrasting Some Differences in Managing Advanced Unresectable Hepatocellular Carcinoma Between the East and the West.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide, although its aetiologies vary significantly between the East and the West. About a half of HCC cases present with advanced unresectable HCC at the time of diagnosis, leading to a worse prognosis. Over the past 20 years, the treatment paradigm for advanced unresectable HCC has shifted from an entirely palliative approach to a multidisciplinary treatment, with continuous reassessment and possible repeat treatment attributed to the advent of novel and improved local, regional and systemic therapeutic options, contributed by both the East and the West. An individualised treatment plan should be determined for each patient, as there can be substantial differences in the decision-making and treatment response to the same treatment for different patients and different patient populations. This review provides a summary of the recent advances in management and compares Eastern and Western strategies for HCC.

Dosimetric analysis of stereotactic rotational versus static intensity-modulated radiation therapy for pancreatic cancer.

PURPOSE: Stereotactic body radiation therapy is a promising treatment modality for locally advanced pancreatic cancer. To determine the optimal radiation treatment, we compared the plan characteristics of volumetric-modulated arc therapy and intensity-modulated radiation therapy when administered with stereotactic body radiation therapy to treat pancreatic cancer. PATIENTS AND METHODS: Fifteen patients with locally advanced pancreatic cancer were treated by stereotactic body radiation therapy at a dose of 24-32Gy in four fractions with marker-guided gated volumetric-modulated arc therapy. Four dimensional-computed tomography scans were used to assess the target and surrounding normal organs. The same images, contours, and dose constraints were used for dual-arc volumetric-modulated arc therapy and 9-field intensity-modulated radiation therapy planning. Plans were compared using dosimetric parameters and treatment performance. RESULTS: Volumetric-modulated arc therapy required significantly lower monitor units (1726 vs. 4188; P<0.001) and shorter treatment delivery time in comparison with intensity-modulated radiation therapy (22.5min vs. 52.4min; P<0.001). Regarding target volume coverage, both modalities demonstrated comparable results (V95%, 99.3% vs. 99.4%; P=0.796). Both modalities satisfied the dosimetric determinants for duodenal toxicity and the maximum and mean doses administered to normal organ were also statistically similar. CONCLUSION: In comparison with 9-field intensity-modulated radiation therapy, volumetric-modulated arc therapy significantly reduces the number of monitoring units and treatment delivery times while administering similar dosimetric quality. Based on these results, volumetric-modulated arc therapy might be an appropriate treatment for locally advanced pancreatic cancer when combined with stereotactic body radiation therapy.

Nanopatterning by ion beam sputtering in unconventional formats.

Nanopatterning at solid surfaces by ion beam sputtering (IBS) has been practiced mostly for stationary substrates with an ion beam incident under a fixed sputter geometry. We have released such constraints in the sputter condition. We simultaneously apply two ion beams or sequentially vary the orientation of substrate with respect to an ion beam. We also periodically change either the azimuthal or polar angle of the substrate with respect to an ion beam during IBS. These unconventional ways of IBS can improve the order of the pattern, and produce novel and non trivial nano patterns that well serve as touch stones to refine the theoretical models and thus deepen our understanding of the patterning mechanisms by IBS.

Stage IE/IIE extranodal NK/T-cell lymphoma arising in the nasal cavity: analysis of CT findings and their prognostic value.

AIM: To investigate the computed tomography (CT) findings in patients with stage IE/IIE extranodal natural killer/T-cell lymphoma (ENKTL) arising in the nasal cavity and to evaluate whether imaging findings revealed by CT have prognostic value. MATERIALS AND METHODS: The CT findings of 62 patients diagnosed with IE/IIE ENKTL arising in the nasal cavity were retrospectively reviewed. Imaging findings were investigated, and evaluated imaging findings were analysed for the prognostic value of overall survival (OS) and disease-free survival (DFS). RESULTS: Of the 62 patients, 21 (34%) presented with a superficial infiltrative, 38 (61%) with a mass forming, and three (5%) with a combined pattern. Of all imaging findings, local invasiveness (n = 26, 42%), including bony destruction, erosion, or soft-tissue involvement, was the only independent prognostic factor for OS [p = 0.008; hazard ratio (HR): 3.85; 95% confidence intervals (CI): 1.42-10.44] and DFS (p = 0.001; HR: 4.25; 95% CI: 1.72-10.47). In a subgroup analysis of 36 cases with no local invasiveness, a superficial infiltrative pattern in one nasal cavity was a positive prognostic factor for OS (p = 0.028) and DFS (p = 0.008). CONCLUSION: Imaging findings at CT provided clinically useful predictions for treatment outcomes. Local invasiveness revealed by CT findings was a strong prognostic factor for poor OS and DFS. In addition, in patients with no local invasiveness, a superficial infiltrative pattern in one nasal cavity predicted favourable OS and DFS.

Prophylactic use of midazolam or propofol at the end of surgery may reduce the incidence of emergence agitation after sevoflurane anaesthesia.

Sevoflurane is associated with a high incidence of emergence agitation in children. Midazolam and propofol have been examined with the aim of reducing emergence agitation after sevoflurane anaesthesia. However the effect of both drugs on emergence agitation is still controversial. Therefore we designed this study to measure the effect of midazolam or propofol at the end of surgery on emergence agitation during the recovery period. One hundred and one children, aged one to 13 years, undergoing strabismus surgery were enrolled in this randomised double-blind study. Anaesthesia was induced and maintained with sevoflurane in N2O/O2. Children were randomly assigned to receive midazolam 0.05 mg/kg (group M, n = 35), propofol 1 mg/kg (group P, n = 31) or saline (group S, n = 35). A four-point scale was used to evaluate recovery characteristics upon awakening and during the first hour after emergence from anaesthesia. The incidence of emergence agitation in group M was 42.9% (15/35), in group P 48.4% (15/31) and in group S 74.3% (26/35). The incidence of emergence agitation in groups M and P was significantly less than in group S. The emergence time was prolonged for patients in groups M and P compared to group S. There was no significant difference in the incidence of emergence agitation or in emergence times between the groups P and M. We conclude that propofol or midazolam administration before the end of surgery may be effective in reducing the incidence of emergence agitation in children undergoing strabismus surgery under sevoflurane anaesthesia.

A comparison of consumption and recovery profiles according to anaesthetic circuit mode using a new multifunctional closed-circuit anaesthesia system during desflurane anaesthesia: a clinical study.

This clinical study compared induction time, consumed anaesthetic dose, and haemodynamic and recovery profiles when using a new type of multifunctional anaesthesia machine (Zeus) in semi-closed or closed circuit modes. Sixty female patients undergoing gynaecological surgery were randomly assigned to three groups and received desflurane anaesthesia through a semi-closed circuit (SCC) at fresh gas flow rates of 4 l/min (SCC 4 l/min) or 2 l/min (SCC 2 l/min), or through a closed circuit (CC). Anaesthesia was maintained at the minimum alveolar concentration for blocking the adrenergic response to painful stimulus (MAC(BAR)) (4.6% end-tidal desflurane) during each operation. The time required to reach MAC(BAR) was significantly shorter and the dose of desflurane was significantly smaller in the CC group compared with the other groups. There were no differences in haemodynamic and recovery profiles between the groups. It is concluded that the CC mode allowed a faster and more reliable induction, lower anaesthetic consumption and stable haemodynamic and recovery profiles.

The effect of increasing operating room capacity on day-of-surgery cancellation.

Several studies have been conducted to evaluate the utilisation of the operating room, a fixed resource, in terms of conditions that prevent day-of-surgery cancellation due to deficient operative capacity. In this study, we surveyed the causes and overall rates of elective surgery cancellation and then compared the number of cancellations that occurred before and after the installation of additional operating rooms. We surveyed all patients undergoing elective surgery for 100 days prior to and after the installation of additional operating rooms. The causes for cancellations were divided into six categories: departmental issues, abnormal laboratory results, patient denial, inadequate preparation, over-booking and other issues. The departmental causes were further divided into four categories: ward overflow, scheduling date errors, unavailable surgeons and other issues. The number of overall cancelled cases and scheduled cases increased following the increase in operating room capacity, although this increase was not statistically significant. However; the cancellation ratio rose significantly after the operating room capacity was increased. The primary reasons for cancellation prior to the increase in operating room capacity were departmental issues, over-booking and abnormal laboratory data, in that order. After the operating room capacity was increased, the primary reasons for cancellation were departmental issues, abnormal laboratory data and over-booking, in that order Taken together the results of this study indicate that increased operating room capacity can prevent cancellation due to over-booking. However; the numbers of cancellations due to ward overflow exceeded the numbers of cancellations that occurred as a result of over-booking. In conclusion, increasing the operating room capacity is not an appropriate option for preventing the cancellation of operations.

Target-controlled propofol infusion for sedation in patients undergoing transrectal ultrasound-guided prostate biopsy.

The efficacy and safety of the routine use of target-controlled infusion of propofol for the sedation of patients undergoing transrectal ultrasound-guided prostate biopsy were assessed. The optimal level of sedation was also evaluated. A total of 250 patients were randomized into five groups according to sedation level determined by the Observer's Assessment of Alertness/Sedation (OAA/S) scale. As the level of sedation was increased, the overall pain and discomfort score decreased and the satisfaction rate tended to increase, although hypoxia meant that intervention occurred more frequently at higher sedation levels. Target-controlled infusion of propofol provided safe and effective sedation during transrectal ultrasound-guided prostate biopsy, particularly if moderate sedation (OAA/S score of 3) was achieved. The effect-site concentration of propofol for this level of sedation was about 1.5 microg/ml.

The clinical values of squamous cell carcinoma antigen and carcinoembryonic antigen in patients with cervical cancer treated with concurrent chemoradiotherapy.

The objective of this study was to determine the prognostic significance of the pre- and posttreatment serum levels of the squamous cell carcinoma antigen (SCC-Ag) and carcinoembryonic antigen (CEA). From 2001 to 2005, 211 patients were treated with concurrent chemoradiotherapy (CCRT). The SCC-Ag and CEA levels were measured before treatment, 1 month after treatment, and during the follow-up. The association between the pretreatment tumor marker levels and the clinical prognostic factors was evaluated. The frequency of complete remission (CR) and the normalization of the posttreatment tumor marker were also analyzed. The pretreatment serum levels of CEA and SCC-Ag were elevated in 68 (32.2%) and 148 (70.1%) patients, respectively. The number of patients with an elevated pretreatment SCC-Ag level was associated with the FIGO stage, tumor volume, and pelvic lymph node status. The pretreatment CEA was only significantly related to the tumor volume and pelvic lymph node involvement. One month after completing CCRT, the CEA and SCC-Ag levels were normalized in almost all patients with an incidence of 88.2% (60/68) and 93.2% (138/148), respectively. Among the patients who gained CR with a previously elevated pretreatment CEA and SCC-Ag, the values were normalized in 92.1% (58/63) and 96.4% (134/139) at 1 month, respectively. Combination assays of the pre- and posttreatment serum CEA and SCC-Ag levels appear to be useful for both predicting the prognosis and estimating the clinical response in cervical cancer. However, the routine combined measurement with SCC-Ag of CEA in all patients had limited additional effect in predicting the prognostic significance.

Thoracic epidural clonidine attenuates haemodynamic responses induced by endobronchial intubation.

Laryngoscopy and endobronchial intubation usually cause transient hypertension and tachycardia. We investigated whether thoracic epidurally injected 3 microg/kg clonidine attenuates cardiovascular responses to intubation compared with 2 microg/kg fentanyl and 1 mg/kg lidocaine. Epidural catheterization was performed at the T6-T7 or T7-T8 intervertebral space, and saline or clonidine in saline was injected 20 min before anaesthetic induction. Anaesthesia was induced using 5 mg/kg thiopental sodium and 0.1 mg/kg vecuronium. Laryngoscopy and endobronchial intubation were performed 2 min later. Mean blood pressure and heart rate were measured throughout anaesthetic induction. In the control group and the fentanyl group, mean blood pressure and heart rate 3 min after endobronchial intubation were elevated significantly compared with baseline. In the clonidine group, however, mean blood pressure and heart rate did not increase compared with baseline. The control group had higher mean blood pressure and heart rate than the clonidine group 3 min after endobronchial intubation. Thoracic epidural clonidine may attenuate the haemodynamic response to endobronchial intubation.

Thymidine phosphorylase expression in tumour cells and tumour response to capecitabine plus docetaxel chemotherapy in non-small cell lung cancer.

BACKGROUND: Thymidine phosphorylase (TP) is the key enzyme for capecitabine activation in tumour cells. AIMS: To examine whether TP expression in tumour cells and stroma is predictive of the tumour response to capecitabine plus docetaxel chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Tumour samples were available from 30 of 39 patients enrolled in a previous phase II study of capecitabine/docetaxel chemotherapy in patients with advanced NSCLC. Stromal and tumour cell TP expression was evaluated by immunohistochemistry using monoclonal antibody PD-ECGF. RESULTS: High tumour cell TP expression was found in 13 of 30 cases and was negatively associated with stromal TP expression (p = 0.000). High stromal TP expression was found in 16 of 28 cases and was strongly associated with intense macrophage infiltration (p = 0.002), suggesting that macrophages are the major component of TP expression in the stroma. Tumour response to capecitabine/docetaxel was significantly associated with high tumour cell TP expression (p = 0.004) and low stromal TP expression (p = 0.009). Moreover, high tumour cell TP expression was significantly associated with severe hand-foot syndrome, a toxic side effect of capecitabine (p = 0.01). Improved survival was seen for high tumour cell and low stromal TP expression, although results were not significant (p = 0.6 and 0.3, respectively). CONCLUSIONS: In advanced NSCLC, TP expression in tumour cells and stroma is associated with tumour response to capecitabine/docetaxel chemotherapy, and might be a useful predictor of tumour response to capecitabine based chemotherapy. A large scale prospective study is needed to confirm the prognostic significance of TP expression in NSCLC.

Prostate shape and symptom score in benign prostatic hyperplasia.

Prostates of the same volumes were found to have very variable shapes, that is, combinations of variably elongated width, height, and lengths. These were believed to be possible causes of the differences in the severity of both the obstructions and symptoms in the prostates even when their volumes were similar. We measured the transverse (width), anterior-posterior (height) and longitudinal (length) diameters of the prostates and the transition zone, and their calculated volumes using transrectal ultrasonography. To establish the relationship between the International Prostate Symptom Score (IPSS) and each of the dimensional parameters of the transition zone and the total prostate, 105 consecutive patients (mean age 66.43 +/- 9.24 years with a range o6f 46 to 90) who had voiding dysfunctions that were presumably related to BPH were analyzed using the t-test. Patients with conditions other than BPH were excluded. The results were as follows: 1. There was no significant correlation between the IPSS and any prostate volume parameter in the constant prostate volume conditions, because of the small numbers in each group. However, in the analysis of the total number of cases in all the volume categories, a significant correlation was found between the IPSS and some prostate dimensions; i.e., the longitudinal parameters in the total prostates (p < 0.01), and the transverse (p < 0.05) and longitudinal parameters (p < 0.05) in the transition zones. 2. Further investigations of the statistics of these significant parameters showed that prostates that were longer than 4 cm had significantly more severe symptoms than prostates shorter than 4 cm (p < 0.05), and that prostates with a ratio of length in the transition zone to the length in the total prostate ratio that was greater than 0.8 had significantly higher symptom scores than those with lower ratios (p < 0.05). When evaluating patients who have BPH, it is important to consider the shape of prostate. More aggressive treatment may be indicated in cases where the transition zone lengths exceeds 4 cm and the transition zone to total prostate length ratio exceeds 0.8.

Local structure analysis of Ti species stabilized in ion exchangeable layer solids by x-ray absorption spectroscopy.

Nano-sized titanium dioxides are incorporated into the interlayer spaces of ion-exchangeable layered perovskites, H(1-x)Ca2(x)La(x)Nb3O10 (x=0.0-0.75), by replacing the interlayer protons with positively charged TiO2 nano-sol particles or basic titanium glycolate complex (titanatrane). Powder X-ray diffraction analysis. UV-Vis absorption spectroscopy, thermogravimetric analysis, and N2 adsorption-desorption isotherm measurements show that quantum sized TiO2 particles are stabilized in between perovskite lattices to form micropores (S(BET) = 37-110 m2/g). X-ray absorption spectroscopy at the Ti K-edge was used for investigating the local environment around Ti atoms constituting the interlayer pillars. According to the XANES spectra, the 'as-pillared' Ti species have the same local environments with those of precursory species, which subsequently converted into TiO2 clusters with rutile and anatase-like local structures when TiO2 nano-sol particles and titanatrane are used as pillaring species. respectively. It is also found that the local environment of TiO2 remains almost constant irrespective of the layer charge density, while the TiO2 pillar content and the microporosity increase with the latter.

The difference in perceptions of educational need between epilepsy patients and medical personnel.

PURPOSE: This study was undertaken to determine what patients with epilepsy need to know about their condition, and to discern what differences exist between patients' perceptions of this need and the medical profession's perception of what patients should know. METHODS: Seventy-five consecutive patients with epilepsy and 56 medical personnel (residents and nurses) who were working in either Neurology or Neurosurgery Units were studied using a structured questionnaire consisting of 3 subsets with a total of 27 questions. RESULTS: Using a Likert scale, epilepsy patients gave high priority to their need for more information about "how epilepsy is diagnosed," "the structure of the brain" (p < 0.05, p < 0.01, respectively), and "the diet that might prevent the attack" (p < 0.05) than did medical personnel. Our study also revealed that men were more concerned with questions regarding smoking and drinking than were women (p < 0.05, respectively), whereas married patients gave higher scores in the category of employment (p < 0.01) and contraception/pregnancy (p < 0.05) than did unmarried patients. The patients with one or more seizures per month rated higher scores on questions concerning the first aid at the time of attack and dosage of antiepileptic drugs (AEDs; p < 0.05, respectively) than did the patients with fewer than one seizure per month. The patients taking poly-AED treatment gave higher scores on six items related to AED therapy than did those receiving monotherapy. No significant differences were found with regard to the length of time patients had the condition, nor to educational level or current employment status. CONCLUSIONS: An educational program for epilepsy patients should be developed on the basis of understanding that there are differences in perspectives among patients with different sociocultural contexts as well as between patients and medical personnel.

Denitrification in submerged biofilters of concentrated-nitrate wastewater.

To understand the possibilities and limitations of the treatment of concentrated nitrate in wastewater, a space-saving biofilm process was introduced to investigate how efficiently concentrated nitrate was utilized in a biofilm process. Lab-scale submerged biofilters stuffed with plastic pall-ring media were developed for the treatment of wastewater containing high nitrate concentration. Two identical biofilters were operated at 2 and 4 hr media HRT in parallel and the concentration of nitrate in the influent was increased stepwise from 50 to 3000 mg-N/L. The concentration of NOx in the effluent was measured at various volumetric loading rates that were proportional to influent nitrate concentrations. There was a critical point for volumetric loading rate (9 kg NO3-N/m3/day) distinguishing the biofilter performances. At the volumetric loading rate below this critical point, the effluent NOx concentration was maintained steadily in spite of the drastic change in the loading rates. However, the effluent NOx concentration severely fluctuated for the small change when the loading rate was higher than the critical point. It was found that the reactor performance was closely related with the biomass concentration (g-dw/ring) in the biofilters.

Location of the chronic subdural haematoma: role of the gravity and cranial morphology.

Chronic subdural haematoma (SDH) frequently originates from subdural hygroma (SDG). The cranial morphology can determine the location of SDG. Since SDG is the precursor of chronic SDH, the shapes of the cranium wall act an important role in location of chronic SDH. The authors tried to test this hypothesis. The computed tomographic scans or magnetic resonance images of 118 consecutive patients with chronic SDH were re-evaluated, and the symmetry of the cranium and location of the lesion were checked. The cranium was symmetrical in 55 patients (47%) and asymmetrical in 63 patients (53%). Chronic SDH was bilateral in 25 patients (21%) and unilateral in 93 patients (79%). It was more commonly bilateral in symmetrical craniums than in asymmetrical craniums (29.1% vs. 14.3%) (p = 0.0496). In 63 patients with asymmetric cranium, the chronic SDH was bilateral in nine patients, located on the opposite side of the flat side in 38 patients, and located on the same side of the flat side in 17 patients. This unequal distribution was statistically significant (p = 0.03). In four patients, the haematoma originated from the acute SDH located on the same side of the flat side. No reason could be found in the remaining 13 patients. Chronic SDH originating from SDG usually locates on the opposite to the flat side of the skull. The shape and posture of the cranium can predict the location of chronic SDH, as in the SDG.

Location of the traumatic subdural hygroma: role of gravity and cranial morphology.

Traumatic subdural hygroma (TSH) is frequently bilateral and locates on the top of the head in a supine position. It suggests that the gravity and cranial posture act a certain role. The authors tried to test this hypothesis. The computed tomographic (CT) scans or magnetic resonance (MR) images of 86 consecutive patients with TSH were re-evaluated. The symmetry of the cranium, the posture of the head during the radiological examinations, and the location of the lesion were all checked. The cranium was symmetrical in 47 patients and asymmetrical in 39 patients. TSH was more commonly bilateral in patients with symmetrical cranium than those with asymmetrical cranium (77% vs 62%). The asymmetrical cranium tended to turn to the flat side. It was more frequently oblique in MR images, which has a long scanning time, than in CT (29% vs 18%). In 39 asymmetric craniums, TSH was bilateral and it was symmetrical in 14 cases. In the remaining 25 cases, TSH located opposite to the flat side in 18 cases. In seven patients with the same side TSHs, four patients had it on the side of atrophy, two on the opposite side of a mass lesion. The gravity and cranial posture can predict the location of TSH. TSH usually occurs at the least pressure in the cranium as a lesion of ex vacuo.

Immunization of burn-patients with a Pseudomonas aeruginosa outer membrane protein vaccine elicits antibodies with protective efficacy.

The aim of this study was to determine whether the antibodies raised in burn patients by active immunization with a Pseudomonas aeruginosa OMPs vaccine have a protective efficacy against infection with P. aeruginosa. The binding patterns with P. aeruginosa OMPs of immunized burn patient sera were similar to the sera of immunized healthy humans as determined by immunoblot and immunoprecipitation analyses. The sera pooled from immunized burn patients after three immunizations showed a significantly higher opsonophagocytic-killing activity than the corresponding pre-immune sera, while the sera from unimmunized patients collected at the same day did not. Passive immunization of mice with post-immune sera of burn patients significantly enhanced the survival rate upon a lethal challenge with P. aeruginosa compared to the pre-immune sera, indicating the protective ability of the antibodies induced in burn patients by immunization. These results suggest that anti-P. aeruginosa OMPs antibodies elicited in burn patients by active immunization are protective against infection with P. aeruginosa, and provide a rational for further development of the vaccine for prevention against P. aeruginosa infection in burn patients.