Short-term results of intrathecal injection of low-dose bupivacaine in outpatients with chronic low back and lower extremity pain.

PURPOSE: To investigate the safety and efficacy of intrathecal injection as an alternative to epidural injection for analgesia. METHODS: Seventy consecutive outpatients with chronic low back and lower extremity pain received lumbar intrathecal injection of low-dose isobaric bupivacaine using a 25-gauge pencil-point needle. The patients received 0.5, 1.0, and 1.5 mg of bupivacaine at 1-week intervals to determine the optimal dose. Thereafter, they received two more weekly injections with the optimal dose. The safety and efficacy of the treatment were assessed over a 1-year period. RESULTS: No serious adverse events were encountered. The optimal dose of bupivacaine (1.0 mg in 60% of patients) alleviated pain and disability (both, p < 0.0001) and provided anesthesia below L1 (L5-T6). Motor block was negligible, and balance impairment improved relative to baseline (p < 0.0001). CONCLUSION: Intrathecal injection of low-dose bupivacaine offers a safe and effective treatment for chronic low back and lower extremity pain. TRIAL REGISTRATION: The study was approved by the Kitasato University Hospital Ethics Committee, and written informed consent was obtained from all individual participants included in the study. This trial was registered with the University Hospital Medical Information Network (UMIN000008670). These slides can be retrieved under electronic supplementary material.

Prospective, randomized, controlled study of the efficacy of transcatheter arterial chemoembolization with miriplatin for hepatocellular carcinoma.

AIM: Transcatheter arterial chemoembolization (TACE) has been recognized as a treatment option for patients with intermediate hepatocellular carcinoma (HCC). This randomized, controlled study compared the local control efficacy of TACE with miriplatin (platinum monohydrate) or with epirubicin. METHODS: The study group consisted of 200 Japanese patients with unresectable HCC treated at the Kitasato University East Hospital (Sagamihara, Japan) between July 2010 and June 2013. The primary end-point of the study was time to tumor progression (TTP). RESULTS: We analyzed 198 patients (99 in the miriplatin group and 99 in the epirubicin group) treated with TACE. The median TTP in the epirubicin group was 5.9 months (95% confidence interval [CI], 4.8-7.0) and 7.6 months (95% CI, 5.8-9.4) in the miriplatin group. There was a significant difference between the two groups (P = 0.021; risk ratio, 1.488; 95% CI: 1.061-2.086). In the epirubicin group, 53 patients (53%) had complete response, 24 patients (24%) had partial response, 12 patients (12%) had stable disease, and 10 patients (10%) had progressive disease. In the miriplatin group, 38 patients (38%) had complete response, 41 patients (41%) had partial response, 2 patients (2%) had stable disease, and 18 patients (18%) had progressive disease. There was no significant difference in the response rate (P = 0.862). Overall incidences of adverse events and adverse drug reactions did not differ significantly between the two groups. CONCLUSION: Miriplatin proved more effective than epirubicin in TACE for unresectable HCC. The trial described in this work has been registered under the trial number: UMIN000004790.

Benefits and problems of transarterial therapy in patients with hepatocellular carcinoma and chronic kidney disease.

PURPOSE: To evaluate the feasibility of transarterial therapy (transcatheter arterial chemoembolization and transcatheter arterial infusion) for patients with hepatocellular carcinoma and chronic kidney disease (CKD). MATERIALS AND METHODS: The study enrolled 35 patients who received transarterial therapy. The patients were classified into a CKD group (n = 10 nondialysis chronic kidney disease [NDCKD] and n = 9 end-stage renal disease [ESRD]) or a non-CKD group (n = 16). The survival rates between the two groups were compared using two different starting points: (a) from initial diagnosis of hepatocellular carcinoma and (b) from enrollment in the study. The tolerance of transarterial therapy in patients with CKD was evaluated by comparing the incidence of major adverse events. RESULTS: The 2-year and 5-year survival rates from initial diagnosis were 83.9% and 53.8% in the CKD group and 70.1% and 40.4% in the non-CKD group (P = .478). The corresponding 3-year survival rate from enrollment in the two groups was 25.6% and 41.2%, respectively (P = .995). The 2-year and 5-year survival rates from initial diagnosis were 70.1% and 40.4% in the non-CKD group, 90.0% and 39.4% in NDCKD patients, and 76.2% and 76.2% in ESRD patients (P = .380). The corresponding 2-year survival rates from enrollment in these groups were 54.9%, 48.0%, and 48.6% (P = .943). Severe contrast-induced nephropathy (n = 3) and late-onset death caused by cholesterol crystal embolism (n = 1) were observed in the NDCKD group. CONCLUSIONS: Transcatheter arterial chemoembolization is feasible in patients with CKD by instituting periprocedural hemodialysis with similar 2-year and 5-year survival compared with patients without CKD.

Carbon dioxide-enhanced angiography for detection of colonic diverticular bleeding and clinical outcomes.

PURPOSE: To determine the ability of CO2-enhanced angiography to detect active diverticular bleeding that is not detected by iodinated contrast medium (ICM)-enhanced angiography and its impact on clinical outcomes when used to confirm embolization, particularly the risks of rebleeding and ischemic complications. MATERIALS AND METHODS: We retrospectively identified a cohort of patients with colonic diverticular bleeding who underwent catheter angiography between August 2008 and May 2023 at our institution. We divided them according to whether they underwent CO2 angiography following a negative ICM angiography study or to confirm hemostasis post-embolization (the CO2 angiography group) or ICM angiography alone in the absence of active bleeding or for confirmation of hemostasis post-embolization (the ICM angiography group). The ability to detect active colonic diverticular bleeding and clinical outcomes were compared between the two groups. RESULTS: There were 31 patients in the ICM angiography group and 29 in the CO2 angiography group. The rate of detection of active bleeding by CO2 angiography that was not identified by ICM angiography was 48%. The rebleeding rate was 23% in the ICM angiography group and 6.9% in the CO2 angiography group. Among the patients who underwent TAE, the ischemic complications rate was 7.1% in the ICM angiography group and 4.5% in the CO2 angiography group. CONCLUSIONS: CO2 angiography may detect active diverticular bleeding that is not detectable by ICM angiography and appears to be associated with a lower rebleeding rate. LEVEL OF EVIDENCE: IV.

SIZE-SPECIFIC DOSE ESTIMATES IN PEDIATRIC BRAIN CT IN RELATION TO AGE AND WEIGHT.

The size-specific dose estimate (SSDE) is used for radiation dose management in computed tomography (CT) and represents patient's absorbed dose more accurately than volume CT dose index. The relationship between SSDE and age or weight was investigated using 980 pediatric brain CT scans. Monolinear, power, and bilinear functions were fitted to the plots of SSDE against age or weight, and SSDE was estimated using the obtained functions. SSDE showed a biphasic increase with increasing age and weight: a rapid initial increase and subsequent a slow increase. Bilinear and power functions were successfully fitted to the plots, and mean estimation errors were close to 0, irrespective of the age or weight group. The standard SSDE values estimated from the obtained functions agreed well with the median values for each age or weight group. The curve-fitting method is expected to aid radiation dose management for pediatric brain CT using SSDE.

Rubella virus as a possible etiological agent of Fuchs heterochromic iridocyclitis.

BACKGROUND: To determine whether rubella virus is involved in the pathogenesis of Fuchs heterochromic iridocyclitis (FHI). METHODS: Fourteen patients (14 eyes) diagnosed with FHI based on characteristic ocular manifestations and eight control subjects were studied. Aqueous humor (AH) samples from 14 FHI patients and one vitreous sample from a FHI patient were analyzed for intraocular antibody production against rubella virus by calculation of the Goldmann-Witmer coefficient (GWC). Viral detection by nested polymerase chain reaction and isolation by culture in RK-13 cells were conducted in nine FHI patients. In addition to laboratory examinations, medical history of rubella virus vaccination was also obtained. RESULTS: Ten patients with FHI examined showed intraocular synthesis of rubella virus antibodies (GWC > 3). A high index of rubella virus antibody production was also found in the vitreous sample (GWC = 30.6). GWC in all control subjects were below detectable level. The rubella genome was detected in two of nine patients, and rubella virus was isolated from one of nine patients with FHI. None of the patients with FHI had been vaccinated against rubella. CONCLUSIONS: Our laboratory data strongly suggest a relationship between FHI and rubella virus.

Analysis of expressed sequence tags from the fungus Aspergillus oryzae cultured under different conditions.

We performed random sequencing of cDNAs from nine biologically or industrially important cultures of the industrially valuable fungus Aspergillus oryzae to obtain expressed sequence tags (ESTs). Consequently, 21 446 raw ESTs were accumulated and subsequently assembled to 7589 non-redundant consensus sequences (contigs). Among all contigs, 5491 (72.4%) were derived from only a particular culture. These included 4735 (62.4%) singletons, i.e. lone ESTs overlapping with no others. These data showed that consideration of culture grown under various conditions as cDNA sources enabled efficient collection of ESTs. BLAST searches against the public databases showed that 2953 (38.9%) of the EST contigs showed significant similarities to deposited sequences with known functions, 793 (10.5%) were similar to hypothetical proteins, and the remaining 3843 (50.6%) showed no significant similarity to sequences in the databases. Culture-specific contigs were extracted on the basis of the EST frequency normalized by the total number for each culture condition. In addition, contig sequences were compared with sequence sets in eukaryotic orthologous groups (KOGs), and classified into the KOG functional categories.

Molecular assembly of artificial photosynthetic antenna core complex on an amino-terminated ITO electrode.

Bacterial photosynthetic membrane proteins, light-harvesting antenna complex (LH1), reaction center (RC), and their combined 'core' complex (LH1-RC) are functional elements in the primary photosynthetic events, i.e., capturing and transferring light energy and subsequent charge separation. These photosynthetic units (PSUs) isolated from Rhodospirillum rubrum (Rs. rubrum) were assembled onto an ITO electrode modified with 3-aminopropyltriethoxysilane (APS-ITO). The near IR absorption spectra of PSUs on the assembled electrodes were identical to those of solutions, indicating that the LH1 and LH1-RC core complexes were native on the electrode. Photocurrent response of PSUs on the electrode was examined upon illumination of the LH1 complex at 880 nm. The LH1-RC and a mixed assembly of LH1 and RC exhibited photocurrent response, but not LH1 only, consistent with the function of these PSUs, capturing light energy and transferring electron. This result provides useful methodology for building an artificial fabrication of PSUs on the electrode.

Image Non-Uniformity Correction for 3-T Gd-EOB-DTPA-Enhanced MR Imaging of the Liver.

PURPOSE: Image non-uniformity may cause substantial problems in magnetic resonance (MR) imaging especially when a 3-T scanner is used. We evaluated the effect of image non-uniformity correction in gadolinium ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MR imaging using a 3-T scanner. METHODS: Two commercially available methods for image non-uniformity correction, surface coil intensity correction (SCIC), and phased-array uniformity enhancement (PURE), were applied to Gd-EOB-DTPA-enhanced images acquired at 3-T in 20 patients. The calibration images were used for PURE and not for SCIC. Uniformity in the liver signal was evaluated visually and using histogram analysis. The liver-to-muscle signal ratio (LMR) and liver-to-spleen signal ratio (LSR) were estimated, and the contrast enhancement ratio (CER) was calculated from the liver signal, LMR, and LSR. RESULTS: Without non-uniformity correction, hyperintensity was consistently observed near the liver surface. Both SCIC and PURE improved uniformity in the liver signal; however, the superficial hyperintensity remained after the application of SCIC, especially in the hepatobiliary-phase images, and focal hyperintensity was shown in the lateral segment of the left hepatic lobe after the application of PURE. PURE increased LMR dramatically and LSR mildly, with no changes in CERs. SCIC depressed temporal changes in LMR and LSR and obscured contrast effects, regardless of the method used for calculation of CER. CONCLUSION: SCIC improves uniformity in the liver signal; however, it is not suitable for a quantitative assessment of contrast effects. PURE is indicated to be a useful method for non-uniformity correction in Gd-EOB-DTPA-enhanced MR imaging using a 3-T scanner.

Carnosine activates the CREB pathway in Caco-2 cells.

Imidazole dipeptide, carnosine, is a versatile compound composed of ß-Ala and L-His. A recent study showed that carnosine might benefit the treatment of Alzheimer's disease and the maintenance of cognitive function. Based on the observation that carnosine is immediately degraded by serum carnosinase, we hypothesized that carnosine improves brain function by promoting brain-gut interaction. This study sought to present possible mechanisms regulating carnosine-induced activation of brain-gut interaction. We had previously found that carnosine augmented the expression of BDNF in human colorectal cancer cells, thus we became interested in cAMP-responsive element binding protein (CREB), which is a dominant regulator of BDNF transcription. We found that carnosine activates CREB and CREB-related pathways by activating Ca2+-related pathways. Our findings suggest that carnosine augments the expression of CREB-regulated genes in the intestine; this augmentation contributes to the carnosine-induced activation of brain-gut interaction.

Involvement of the NFX1-repressor complex in PKC-δ-induced repression of hTERT transcription.

The human telomerase reverse transcriptase (hTERT) gene encodes an enzyme responsible for maintaining the integrity of chromosomal ends. hTERT plays a key role in cellular immortalization, tumorigenesis and the progression of cancer. Previously, we reported that hTERT repression is required for the induction of cellular senescence. Thus, transcriptional regulation mechanisms of the hTERT gene may be related to the mechanisms of cellular senescence. In the present study, we clarified the molecular mechanism of hTERT repression by protein kinase C (PKC)-δ, one of the cellular senescence-inducing factors. The results showed that a repressor complex composed of NFX1-91, mSin3A and histone deacetylase 1 was involved in the PKC-δ-induced repression of the hTERT promoter, which resulted in the repression of hTERT transcription. These results suggest that targeted recruitment of the NFX1-91 complex to the hTERT promoter is a potential mechanism for repressing hTERT transcription and further inducing cellular senescence.

Evaluation of a respiratory navigator-gating technique in Gd-EOB-DTPA-enhanced magnetic resonance imaging for the assessment of liver tumors.

OBJECTIVES: We investigated the clinical usefulness of respiratory navigator-gating technique for the assessment of liver tumors in Gd-EOB-DTPA-enhanced magnetic resonance (MR) imaging. METHODS: Eighty patients who underwent Gd-EOB-DTPA-enhanced MR imaging to evaluate known or suspected liver tumors were enrolled. Three-dimensional spoiled gradient-recalled echo images of the liver were acquired in the hepatobiliary phase by the following three methods: breath-hold imaging, navigator-gated low-resolution imaging, and navigator-gated high-resolution imaging. Navigator-gated imaging was performed during free breathing. Spatial resolution was identical between breath-hold imaging and gated low-resolution imaging. Signal intensities in the liver, muscle, and spleen were measured in 20 patients. Image quality was visually evaluated in all 80 patients. The detection rate and lesion conspicuity were assessed for 71 malignant liver lesions identified in 29 patients. RESULTS: The liver-to-muscle and liver-to-spleen signal ratios were significantly lower for gated images compared to breath-hold images. Images of acceptable quality were obtained in most patients by all three methods, and the overall image quality of axial images did not differ significantly among the imaging methods, although superior reformatted coronal images were obtained by gated high-resolution imaging. The detection rates of malignant liver lesions were similar among the three imaging methods, although lesion conspicuity was significantly better for breath-hold imaging compared to gated imaging. CONCLUSIONS: Navigator-gated imaging provided image qualities and detection rates of malignant liver lesions comparable to breath-hold imaging in Gd-EOB-DTPA-enhanced MR imaging; however, no additional benefits of high-resolution imaging were proven for lesion evaluation.

Effects of laser in situ keratomileusis on mental health-related quality of life.

PURPOSE: The aims of our study were to investigate whether laser in situ keratomileusis (LASIK) improves health-related quality of life (HRQoL) and to identify factors that affect postoperative HRQoL. MATERIALS AND METHODS: A total of 213 Japanese patients who underwent primary LASIK were analyzed in this study. The average age of patients was 35.0±9.4 years. The subjects were asked to answer questions regarding subjective quality of vision, satisfaction, and quality of life (using the Japanese version of 36-Item Short Form Health Survey Version 2) at three time points: before LASIK, 1 month after LASIK, and 6 months after LASIK. Longitudinal changes over 6 months in the outputs of mental component summary (MCS) score and the physical component summary (PCS) score from the 36-Item Short Form Health Survey Version 2 questionnaire were compared between time points using a linear mixed-effects model. Delta MCS and PCS were calculated by subtracting the postoperative score (1 month after LASIK) from the preoperative score. Preoperative and postoperative factors associated with a change in the MCS score or PCS score were evaluated via a linear regression model. RESULTS: The preoperative MCS score was 51.0±9.4 and increased to 52.0±9.8 and 51.5±9.6 at 1 month and 6 months after LASIK, respectively, and the trend for the change from baseline in MCS through 6 months was significant (P=0.03). PCS score did not change following LASIK. Delta MCS was significantly negatively associated with preoperative spherical equivalent, axial length, and postoperative quality of vision, after adjusting for potential confounding factors. CONCLUSION: Mental HRQoL is not lost with LASIK, and LASIK may improve mental HRQoL. Preoperative axial length may predict postoperative mental HRQoL.

Intraperitoneal bleeding after balloon-occluded retrograde transvenous obliteration: a case report.

INTRODUCTION: Hepatic encephalopathy is an important underlying cause of consciousness disorders. Possible causes of hepatic encephalopathy include hepatic failure and shunt encephalopathy resulting from a portosystemic venous shunt. Balloon-occluded retrograde transvenous obliteration is generally an effective treatment for hepatic encephalopathy. CASE PRESENTATION: A 73-year-old Japanese woman was referred to our department because of disturbance of consciousness. Hepatic venous angiography disclosed a shunt between her left hepatic vein and her portal vein. The shunt was closed with the use of coils and N-butyl 2-cyanoacrylate. One hour after the procedure, she lost consciousness. The bleeding was ascribed to catheter-induced vascular injury. Emergency angiography was performed, and hemostasis was achieved with coils. CONCLUSION: Although bleeding is relatively rare after balloon-occluded retrograde transvenous obliteration, postoperative intraperitoneal bleeding is a serious complication.

Impaired ATP6V0A2 expression contributes to Golgi dispersion and glycosylation changes in senescent cells.

Many genes and signaling pathways have been found to be involved in cellular senescence program. In the present study, we have identified 16 senescence-associated genes by differential proteomic analysis of the normal human diploid fibroblast cell line, TIG-1, and focused on ATP6V0A2. The aim of this study is to clarify the role of ATP6V0A2, the causal gene for ARCL2, a syndrome of abnormal glycosylation and impaired Golgi trafficking, in cellular senescence program. Here we showed that ATP6V0A2 is critical for cellular senescence; impaired expression of ATP6V0A2 disperses the Golgi structure and triggers senescence, suggesting that ATP6V0A2 mediates these processes. FITC-lectin staining and glycoblotting revealed significantly different glycosylation structures in presenescent (young) and senescent (old) TIG-1 cells; reducing ATP6V0A2 expression in young TIG-1 cells yielded structures similar to those in old TIG-1 cells. Our results suggest that senescence-associated impaired expression of ATP6V0A2 triggers changes in Golgi structure and glycosylation in old TIG-1 cells, which demonstrates a role of ATP6V0A2 in cellular senescence program.

Organization of Actin Filaments and Zonula Adherens during Somitogenesis in the Chick Embryo: (somitogenesis/actin/zonula adherens/chick embryo).

The organization of F-actin during somitogenesis in the chick embryo was studied by use of rhodamine-conjugated phalloidin and transmission electron microscopy (TEM). Separation of a somite from the segmental plate proceeded simultaneously with the organization of segmental plate cells into a hemispherical epithelial sheet whose open side was directed antero-laterally. At the same time, intense staining of F-actin appeared in the apical surface of the epithelial sheet. Observations by TEM showed that zonulae adherentes associated with many actin filaments increased in the apical region of cells being organized into an epithelial sheet while this junctional apparatus was only sparsely distributed in the segmental plate cells. The hemispherical sheet subsequently closed to form an epithelial vesicle, with increase in curvature of its apical surface, and narrowing of cellular apices. At the same time, the zonulae adherentes and actin filaments in the cellular apices further increased, and many cellular processes formed on the apical surface of the epithelial somites. These findings suggest that segmentation involves organization of zonulae adherentes and a contractile process caused by acin filaments anchored to the zonulae adherentes.

Successful treatment of acquired uterine arterial venous malformation using N-butyl-2-cyanoacrylate under balloon occlusion.

We present two cases of acquired uterine arterial venous malformation (AVM) which was diagnosed because of massive genital bleeding successfully treated with transcatheter arterial embolization (TAE), using N-butyl-2-cyanoacrylate (NBCA) under balloon occlusion. Balloon occlusion at the uterine artery was performed in both patients for diffuse distribution of NBCA in multiple feeding branches, as well as to the pseudoaneurysm, and for the prevention of NBCA reflux. In one of our patients, balloon occlusion of the draining vein was simultaneously performed to prevent NBCA migration through accompanying high-flow arteriovenous fistula (AVF). Doppler ultrasound at 6 months of both patients documented persistent complete occlusion of AVM. Complete and safe obliteration of acquired uterine AVM was accomplished using NBCA as embolic agent, under balloon occlusion at the communicating vessels of acquired uterine AVM.

In vitro immunization of Epstein-Barr virus-immortalized B cells augments antigen-specific antibody production.

The current method for in vitro immunization (IVI) uses several antigens including toxins, food allergens, pathogenic bacteria, and self-antigen-derived peptides that induce an antigen-specific immune response in peripheral blood mononuclear cells (PBMCs). This protocol, however, requires donor blood collection and preparation of PBMCs before every IVI. In the present study, we aimed to design a more efficient system utilizing B cells immortalized with Epstein-Barr virus (EBV-B) as host cells for IVI to make antigen-specific antibodies. Results showed that previously antigen-sensitized, EBV-B cells exposed to the antigen along with IL-6, CpG oligonucleotides, and CD40 ligand signal produced antigen-specific antibodies. These results provide evidence for a novel and easy method to expand memory-type B cells and produce antigen-specific antibodies.