Are patients with mild to moderate renal impairment on metformin or other oral anti-hyperglycaemic agents at increased risk of contrast-induced nephropathy and metabolic acidosis after radiocontrast exposure?

AIM: To investigate whether the use of metformin during computed tomography (CT) with radiocontrast agents increases the risk of contrast-induced nephropathy (CIN) and metabolic acidosis after CT in type 2 diabetes patients with mild to moderate renal failure. MATERIALS AND METHODS: Patient records from January 2015 to December 2017 were reviewed retrospectively. A total of 374 patients were included in the final analysis. Of them, 157 patients received metformin, and 217 patients were taking other oral hypoglycaemic agents (OHAs) during radiocontrast administration. RESULTS: No significant difference in CIN incidence was observed between the metformin use group and the other OHAs group (p=0.085). Metabolic acidosis after CT was seen in 91 (58%) patients who used metformin and 141 (65%) patients who were taking other OHAs. There was no relationship between metabolic acidosis after CT and the use of metformin (p=0.195). Metabolic acidosis after radiocontrast agent exposure was associated with malignant disease, low serum albumin level, and low serum total CO2 level at baseline. CONCLUSION: These data show that other factors, but not metformin use, are associated with metabolic acidosis after radiocontrast agent exposure in patients with reduced renal function. These data support current recommendations that there is no need to discontinue metformin before CT using radiocontrast agents in patients with mild to moderate renal failure.

Sequence variations of the locus-specific 5' untranslated regions of SLA class I genes and the development of a comprehensive genomic DNA-based high-resolution typing method for SLA-2.

The genetic diversity of the major histocompatibility complex (MHC) class I molecules of pigs has not been well characterized. Therefore, the influence of MHC genetic diversity on the immune-related traits of pigs, including disease resistance and other MHC-dependent traits, is not well understood. Here, we attempted to develop an efficient method for systemic analysis of the polymorphisms in the epitope-binding region of swine leukocyte antigens (SLA) class I genes. We performed a comparative analysis of the last 92 bp of the 5' untranslated region (UTR) to the beginning of exon 4 of six SLA classical class I-related genes, SLA-1, -2, -3, -4, -5, and -9, from 36 different sequences. Based on this information, we developed a genomic polymerase chain reaction (PCR) and direct sequencing-based comprehensive typing method for SLA-2. We successfully typed SLA-2 from 400 pigs and 8 cell lines, consisting of 9 different pig breeds, and identified 49 SLA-2 alleles, including 31 previously reported alleles and 18 new alleles. We observed differences in the composition of SLA-2 alleles among different breeds. Our method can be used to study other SLA class I loci and to deepen our knowledge of MHC class I genes in pigs.

Clinical significance of serum bilirubin and gamma-glutamyltransferase levels on coronary atherosclerosis assessed by multidetector computed tomography.

BACKGROUND AND AIMS: Low bilirubin and high gamma-glutamyltransferase (GGT), which are endogenous markers of oxidative stress, confer a higher risk of cardiovascular disease (CVD). We investigated associations between serum concentrations of bilirubin, GGT and coronary atherosclerosis. METHODS AND RESULTS: A cross-sectional analysis was performed on 1520 subjects who underwent multidetector computed tomography scans. Coronary atherosclerosis was assessed by coronary artery calcium score (CACS) and obstructive coronary artery disease (OCAD), was defined as the presence of coronary artery stenosis of ≥50%. Total bilirubin (TB) level was negatively correlated with CACS and coronary stenosis whereas GGT level was positively correlated with CACS in men. However, there was no correlation between TB, GGT levels and either CACS or coronary artery stenosis in women. In a multivariate-adjusted model, TB level was inversely associated with a CACS > 100 [odds ratio (OR) per log standard deviation (SD), 0.67; 95% confidence interval (CI), 0.52-0.87], and OCAD (OR per log SD, 0.77; 95% CI, 0.62-0.95) in men. By contrast, GGT level was positively associated with a CACS > 100 (OR per log SD, 1.35; 95% CI, 1.05-1.73) but not with OCAD. Adding TB and GGT to the conventional risk factors increased predictive accuracy for CACS > 100 (net reclassification improvement index [NRI] = 13.1%, P = 0.026; integrated discrimination index [IDI] = 0.024, P = 0.001) and for OCAD (NRI = 12.6%, P = 0.026; IDI = 0.010, P = 0.013). CONCLUSIONS: Low TB and high GGT levels were concomitantly associated with coronary atherosclerosis in Korean men. Future studies are needed to elucidate the causal associations of TB and GGT with CVD.

Rhabdomyolysis associated with initiation of febuxostat therapy for hyperuricaemia in a patient with chronic kidney disease.

WHAT IS KNOWN AND OBJECTIVE: Febuxostat is now recommended as the first-line pharmacological urate-lowering therapy for gout in the American College of Rheumatology guidelines. There is no case of rhabdomyolysis associated with febuxostat among reported side effects of the drug. Our objective is to report on a case of rhabdomyolysis associated with initiation of febuxostat in a patient with chronic kidney disease (CKD). CASE SUMMARY: A 73-year-old male patient visited our emergency room due to progressive weakness in both lower extremities starting 3 days earlier. Ten days before presentation, his primary physician had changed his prescription from allopurinol to febuxostat (80 mg) because of poor control of uric acid levels. There was tenderness in both thighs. Initial creatinine kinase (CK) was 7652 U/L (0-170 U/L), and a bone scan using (99m) Tc-HDP revealed strong uptake in soft tissues in both thighs and buttocks. Electromyography (EMG) and nerve conduction velocity (NCV) showed abnormal spontaneous activities (ASA), suggesting myopathy, not nerve damage. On day 7 of admission, after conservative management and febuxostat withdrawal, he could walk on the ward. He is being followed in our clinic as an outpatient with no sequelae. WHAT IS NEW AND CONCLUSION: This report is first case of rhabdomyolysis associated with initiation of febuxostat. Febuxostat should be withdrawn when rhabdomyolysis is confirmed.

Effect of bovine follicular fluid on reactive oxygen species and glutathione in oocytes, apoptosis and apoptosis-related gene expression of in vitro-produced blastocysts.

The reactive oxygen species (ROS) generated during the in vitro maturation of oocytes affect oocyte maturation and subsequent embryonic development. Bovine follicular fluid (bFF) has an effective antioxidant capacity. This study was conducted to investigate the effects of supplementing oocyte maturation media with bFF from different size classes (3-8 and 9-13 mm) on the glutathione (GSH) and ROS levels of oocytes. Embryonic development and apoptosis, as well as the relative abundance of INFτ, BAX, BCL2 and HSP70 transcripts in blastocysts, were also monitored. Oocytes collected from ovaries were matured in TCM-199 with FBS (control) and 10% 3-8 mm (M), 9-13 mm (L) or a mixture of 3-8 mm and 9-13 mm (M + L) bFF. Glutathione and ROS levels in oocytes after 24 h were assessed by Cell Tracker Blue CMF2HC and DCHFDA staining, respectively. Apoptosis in day-8 blastocysts was assessed by TUNEL staining. The relative abundance of BAX, BCL2, HSP70 and INFτ transcripts was assessed using quantitative real-time polymerase chain reaction (PCR). The GSH level was significantly higher in the L group compared to the other groups (p < 0.05), while the ROS levels in the M group were significantly higher than in the other groups (p < 0.05). The apoptosis levels of blastocysts in the FBS group were significantly higher than those in the M + L group (p < 0.05), although the embryonic development did not differ between the groups. The HSP70 and INFτ expression levels in group M were significantly greater than in the controls (p < 0.05). There was no significant difference in BAX expression between the groups. Supplementation with bFF from various sizes of follicles into the maturation medium was capable of supporting oocyte cytoplasmic maturation by decreasing the ROS. Moreover, bFF subsequently affected antioxidative gene expression, increasing HSP70 and INFτ expressions.

A comparison of the BURP and conventional and modified jaw thrust manoeuvres for orotracheal intubation using the Clarus Video System.

We evaluated the effects of three airway manipulation manoeuvres: (a) conventional (single-handed chin lift); (b) backward, upward and right-sided pressure (BURP) manoeuvre; and (c) modified jaw thrust manoeuvre (two-handed aided by an assistant) on laryngeal view and intubation time using the Clarus Video System in 215 patients undergoing general anaesthesia with orotracheal intubation. In the first part of this study, the laryngeal view was recorded as a modified Cormack-Lehane grade with each manoeuvre. In the second part, intubation was performed using the assigned airway manipulation. The primary outcome was the time to intubation, and the secondary outcomes were the modified Cormack-Lehane grade, the number of attempts and the overall success rate. There were significant differences in modified Cormack-Lehane grade between the three airway manipulations (p < 0.0001). Post-hoc analysis indicated that the modified jaw thrust improved the laryngeal view compared with the conventional (p < 0.0001) and the BURP manoeuvres (p < 0.0001). The BURP worsened the laryngeal view compared with the conventional manoeuvre (p = 0.0132). The time to intubation in the modified jaw thrust group was shorter than with the conventional manoeuvre (p = 0.0004) and the BURP group (p < 0.0001). We conclude that the modified jaw thrust is the most effective manoeuvre at improving the laryngeal view and shortening intubation time with the Clarus Video System.

Biomechanical evaluation of the impact of collared cementless total hip arthroplasty stems on implant subsidence: a cadaveric study in German Shepherd.

Background: With the increasing use of cementless total hip arthroplasty (THA), stem subsidence has emerged as one of the primary complications. Although electron beam melting (EBM)-manufactured stems have been demonstrated to prevent subsidence, there has been limited investigation into the comparative biomechanical impact of collarless and collared EBM cementless stems on stem subsidence in veterinary medicine. Aims: This study aimed to compare the stem implant resistance and failure mechanical properties between collarless and collared EBM-manufactured stems. Methods: Seven pairs of femurs were harvested from canine cadavers. In each pair of femurs, the left femur was implanted with a collarless, and the right femur with a same-sized collared cementless stem. Specimen constructs were mounted to the loading frame of a testing machine and load was transferred to the femoral stem parallel to the longitudinal axis of the femur until the stem subsided 5 mm. Load and stem displacement data acquired during the tests were used to generate load-displacement curves and obtain stiffness, yield, and failure data for each specimen construct. Yield and failure energies were calculated as the areas under the load-displacement curves to the respective points. The effects of implant type and load during subsidence were analyzed using paired t-tests. Results: The yield and failure loads for the collared stems were approximately 40% greater than for the collarless stems (156.39 ± 43.63 kgf vs. 112.01 ± 59.83 kgf, P<0.05). Conclusion: This study supported the advantages of collared EBM stems, including subsidence prevention and better initial stability for early osteointegration.

The influence of patient position on withdrawal force of thoracic epidural catheters.

We investigated the forces required to remove thoracic epidural catheters to determine the effect of patient position on removal. Eighty-four patients undergoing open thoracotomy and thoracic patient-controlled epidural analgesia were enrolled. Catheterisation was performed under fluoroscopic guidance before surgery, and the patients were allocated to one of three position groups for removal: prone; sitting; and lateral. On the third postoperative day, the peak tension during withdrawal in the assigned position was measured. No differences in mean (SD) forces were found between groups: prone 1.61 (0.39) N, supine 1.62 (0.61) N and lateral 1.36 (0.56) N (p = 0.140). The withdrawal forces required to remove thoracic epidural catheters were not affected by the position. Thus, the position for removal can be determined by patient's choice and clinical judgement.

BioCARS: a synchrotron resource for time-resolved X-ray science.

BioCARS, a NIH-supported national user facility for macromolecular time-resolved X-ray crystallography at the Advanced Photon Source (APS), has recently completed commissioning of an upgraded undulator-based beamline optimized for single-shot laser-pump X-ray-probe measurements with time resolution as short as 100 ps. The source consists of two in-line undulators with periods of 23 and 27 mm that together provide high-flux pink-beam capability at 12 keV as well as first-harmonic coverage from 6.8 to 19 keV. A high-heat-load chopper reduces the average power load on downstream components, thereby preserving the surface figure of a Kirkpatrick-Baez mirror system capable of focusing the X-ray beam to a spot size of 90 µm horizontal by 20 µm vertical. A high-speed chopper isolates single X-ray pulses at 1 kHz in both hybrid and 24-bunch modes of the APS storage ring. In hybrid mode each isolated X-ray pulse delivers up to ~4 × 10(10) photons to the sample, thereby achieving a time-averaged flux approaching that of fourth-generation X-FEL sources. A new high-power picosecond laser system delivers pulses tunable over the wavelength range 450-2000 nm. These pulses are synchronized to the storage-ring RF clock with long-term stability better than 10 ps RMS. Monochromatic experimental capability with Biosafety Level 3 certification has been retained.

Visit-to-visit changes in fasting blood sugar and the risk for cardiovascular disease and mortality in the Korean population: a nationwide population-based cohort study.

OBJECTIVE: The importance of continuous monitoring of fasting blood sugar (FBS) levels of diabetic patients has been established. MATERIALS AND METHODS: An observational prospective study was conducted. Our analysis included 1,700,796 individuals from the nationwide South Korean National Health Insurance System cohort. FBS variability was measured by standard deviation (SD). RESULTS: Kaplan-Meier curves demonstrated elevated disease probability in the higher FBS fluctuation group compared with the lower FBS fluctuation group. After adjusting for confounding variables, Cox proportional hazards analysis showed that the hazard ratios of 411 individuals in the highest quartile of SD variation of FBS were 1.77 (95% confidence interval 1.37-2.28, p<0.001) compared with the lowest quartile of SD variation of FBS. The impact of FBS fluctuation on the risk of cardiovascular diseases (CVDs), cerebrovascular diseases, CVD mortality and all-cause mortality in the highest quartiles of diabetic and non-diabetic individuals was statistically significant. CONCLUSIONS: Visit-to-visit FBS variability has prognostic value for predicting micro- and macrovascular disease, cardiovascular mortality, and all-cause mortality.

Risk of intravascular injection in transforaminal epidural injections.

Transforaminal epidural injection is an effective method for treating spinal pain but can cause devastating complications that result from accidental vascular uptake of the injectate or a direct vascular injury. We prospectively evaluated the patient factors that might be associated with intravascular uptake during transforaminal epidural injections. A total of 2145 injections were performed on 1088 patients under contrast-enhanced real-time fluoroscopic guidance. The collected data included the patient's age, sex, body mass index, diagnosis, injection level, side of injection, history of spinal surgery at the targeted level, and the number of injections at the targeted site. The overall incidence of intravascular injection was 10.5% (224/2145). The highest incidence was at the cervical level (28/136; 20.6%), followed by the sacral level (111/673; 16.5%), the thoracic level (23/280; 8.2%) and the lumbar level (64/1056; 6.1%). The difference was significant for the cervical and sacral level compared with the lumbar and thoracic levels (p < 0.001). Intravascular injection was not associated with the other patient characteristics studied.

Hypertrophic osteopathy associated with aortic thrombosis in a dog.

BACKGROUND: Aortic thrombosis (ATh) is an uncommon problem in dogs. Although the pathogenesis of hypertrophic osteopathy (HO) is unknown, it is thought this can be due to blood flow disorder. In this case, removal of aortic thromboembolism (ATE) resulted in periosteal proliferation. CASE DESCRIPTION: A 4.8-kg, 3-year-old, intact female Maltese was referred with a bite wound showing pneumomediastinum, pneumothorax, and subcutaneous emphysema. After adequate treatment, the dog had recovered well and was discharged. FINDINGS/TREATMENT AND OUTCOME: Acute non-painful paraparesis suddenly developed 5 days after discharge. An abdominal ultrasound showed ATE at the level of 1 cm proximal to the external iliac arterial bifurcation. Based on clinical sign, physical exam, neurologic exam, and ultrasonography, ATh was diagnosed. Arterial thrombectomy was performed to remove the thrombus. Twenty-four days after surgery, the dog had pain and soft tissue swelling of both stifles due to HO. After rehabilitation, the dog finally started to ambulate, and the dorsal pedal arteries pulse was normal. Hypertrophic osteopathy also resolved completely. CONCLUSION: This report suggests the relationship between HO and ATh, for the first time in veterinary medicine.

Simultaneous peripheral tuberculous lymphadenitis and a tuberculous liver abscess in a hemodialysis patient.

A tuberculous liver abscess is an extremely rare condition. However, extrapulmonary tuberculosis is more common in end-stage renal disease patients. We report a 64-year-old woman on hemodialysis with liver cirrhosis. She had no evidence of pulmonary or intestinal tuberculosis on the chest radiograph, abdominal computed tomography (CT), or colonoscopy. She had fever and an enlarged right supraclavicular lymph node. A CT showed several cystic ring-enhancing nodules in the liver. Histopathologic examinations were performed on the enlarged lymph node and a cystic nodule in the liver, which revealed caseating granulomas. Systemic antituberculous therapy was started immediately. A subsequent sonographic examination of the lesion in the liver showed improvement. In end-stage renal disease patients, we should be concerned with extrapulmonary tuberculosis. The diagnosis and antituberculous therapy must be performed promptly.

Production and characterization of monoclonal antibodies against major histocompatibility complex class I chain-related gene A.

Major histocompatibility complex (MHC) class I chain-related gene A (MICA), a ligand for the activating immunoreceptor natural killer group 2D (NKG2D), is expressed on stressed cells such as tumor cells. Study of expression of this molecule on tumor cells and patients' sera is useful to define patients' stages leading to proper selection of therapy. In this study, mouse anti-MICA monoclonal antibodies (mAbs) were produced by DNA immunization using a gene gun. Screening of anti-MICA-producing mouse and hybridomas were performed by immunoblot and cell enzyme-linked immunosorbent assay (ELISA) against MICA-positive HeLa and -negative Me1386 cell lines. MAbs were characterized against MICA-positive and -negative cell lines by immunoblot, cell ELISA and flow cytometry. The mAbs were also characterized for locus and allele specificities of MICA and MHC class I chain-related gene B (MICB) as well as for their ability to stain formalin-fixed paraffin-embedded tissues by immunohistochemistry. Although all mouse immune sera were positive with MICA-positive cells by both immunoblot and cell ELISA methods, some hybridomas were positive only with one method. The mAbs had diverse specificities to detect MICA and MICB and different abilities to stain formalin-fixed paraffin-embedded tissues. Thus, DNA immunization by gene gun is an effective method to generate immune mice for the production of mAbs with a variety of specificities against native and denatured forms of MIC proteins.

The characterization of PCDDs, PCDFs and coplanar PCBs during the past 50 years in Gwangyang Bay, South Korea.

The PCDD/DFs and coplanar PCBs (co-PCBs) in sediment samples from Gwangyang Bay in South Korea was investigated. The total concentration of dioxins and their toxic equivalent quantity (TEQ; calculated with the WHO 2005 Toxic Equivalency Factors) value in the surface sediment of the outer site (261 pg g(-1) TOC, 4.4 pg-TEQ g(-1)) were 3-fold higher than the inner site (90 pg g(-1) TOC, 1.1 pg-TEQ g(-1)) in the Bay. The dioxin in the sediment samples was found to come from a mixture of the impurities of pentachlorophenol (PCP), chloronitrofen (CNP) and combustion based on the result of hierarchical cluster analysis (HCA). These dioxin sources have been influenced by the characterization associated with this region which was both an agricultural-centered and industrial-centered area. According to principal component analysis (PCA) related to the Kow values for the congener-specific composition of co-PCBs in the sediment core, the Kanechlor (KC)-500 and the atmospheric deposition were identified as the possible sources. The maximum burden in the sediment core was 1.3 kg for 1967-1974 and the total burdens of PCDD/DFs and co-PCBs in the sediment core were estimated to be 6.6 kg during the past 50 years. The cumulative burdens of dioxin are still increasing in Gwangyang Bay.

Efficacy of polymers from spontaneous carotenoid oxidation in reducing necrotic enteritis in broilers.

This study evaluated the preventive effect of the spontaneous oxidation of ß-carotene (OxC-beta) in broiler chickens with necrotic enteritis by Clostridium perfringens taking into consideration various parameters including clinical signs, body weight, intestinal lesion severity, and bacterial enumeration. The mean body weight of the OxC-beta treatment groups increased significantly (P < 0.05) compared to that of the C. perfringens challenge group. Intestinal lesion scores due to C. perfringens infection were significantly alleviated by OxC-beta treatment (P < 0.05), and the number of clostridial bacteria in intestine was reduced by OxC-beta in a dose-dependent manner. OxC-beta in feed contributes to the prevention of necrotic enteritis in commercial broiler chicken, and has a positive effect in improving productivity.

Eliminating artifacts in single-grid phase-contrast x-ray imaging for improving image quality.

In this study, we propose a modification to a single-grid phase-contrast x-ray imaging (PCXI) system using a Fourier domain analysis technique to extract absorption, scattering, and differential phase-contrast images. The proposed modification is to rotate the x-ray grid in the image plane to achieve spectral separation between the desired information and the moiré artifact, which is introduced by the superposition of the periodic image of the grid shadow and the periodic sampling by the detector. In addition, we performed some system optimization by adjusting distances between source, object, grid, and detector to further improve image quality. This optimization aimed to increase the spectral spacing between the primary spectrum (lower frequency) and the harmonics of the spectrum (higher frequency) used to extract the various image contrasts. The table-top setup used in the experiment consisted of a focused-linear grid with a 200-lines/inch strip density, a microfocus x-ray tube with a 55-µm focal spot size, and a CMOS flat-panel detector with a 49.5-µm pixel size. The x-ray grid was rotated at 27.8° with respect to the detector and the sample was placed as close as possible to the x-ray tube. Our results indicated that the proposed method effectively eliminated the PCXI artifacts, thus improving image quality.

Phosphoaspartates in bacterial signal transduction.

Bacteria use a strategy referred to as two-component signal transduction to sense a variety of stimuli and initiate an appropriate response. Signal processing begins with proteins referred to as histidine kinases. In most cases, these are membrane-bound receptors that respond to environmental cues. Histidine kinases use ATP as a phosphodonor to phosphorylate a conserved histidine residue. Subsequent transfer of the phosphoryl group to a conserved aspartyl residue in the cognate response regulator results in an appropriate output. Recent structural studies of activated (phosphorylated) response regulators and their aspartate-bearing regulatory domains have provided insight into the links between the chemistry and biology of these ubiquitous regulatory proteins. Chemical aspects of their function appear to generalize broadly to enzymes that adopt a phosphoaspartate intermediate.

Unicameral bone cysts: a comparison of injection of steroid and grafting with autologous bone marrow.

Open surgery is rarely justified for the initial treatment of a unicameral bone cyst, but there is some debate concerning the relative effectiveness of closed methods. This study compared the results of steroid injection with those of autologous bone marrow grafting for the treatment of unicameral bone cysts. Between 1990 and 2001, 30 patients were treated by steroid injection and 28 by grafting with autologous bone marrow. The overall success rates were 86.7% and 92.0%, respectively (p>0.05). The success rate after the initial procedure was 23.3% in the steroid group and 52.0% in those receiving autologous bone marrow (p<0.05), and the respective cumulative success rates after second injections were 63.3% and 80.0% (p>0.05). The mean number of procedures required was 2.19 (1 to 5) and 1.57 (1 to 3) (p<0.05), the mean interval to healing was 12.5 months (4 to 32) and 14.3 months (7 to 36) (p>0.05), and the rate of recurrence after the initial procedure was 41.7% and 13.3% in the steroid and in the autologous bone marrow groups, respectively (p<0.05). Although the overall rates of success of both methods were similar, the steroid group had higher recurrence after a single procedure and required more injections to achieve healing.